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NCT05653258

Single Nuclei RNA-seq to Map Adipose Cellular Populations and Senescent Cells in Older Subjects

All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq and metabolic/physiological assessments (insulin sensitivity, glucose tolerance, and β-cell function). Older obese participants will be randomized into three arms: lifestyle intervention (n=24), senolytics (n=24), or placebo (n=24).

All participants after consent and enrollment will undergo adipose tissue single nuclei RNA sequencing and metabolic phenotyping. Subjects will undergo glucose tolerance testing to document glucose tolerance status. Each subject will be provided an accelerometer to be worn on their dominant wrist for 7 days for assessment of habitual activity.~A dietitian will teach them to utilize the SmartIntake3 smartphone food picture application (app) for a 7-day food record. The app will be used to record amount of each meal consumed in order to determine daily food and beverage and supplement intake and quantity for dietary composition analysis. DEXA analysis will be performed to measure lean and fat body mass.~Subjects will undergo evaluation of physical function/performance, including the Short Physical Performance Battery (SPPB) and VO2 peak testing for assessment of aerobic capacity. The SPPB will be done in older adults only.~The NIH Patient-Reported Outcomes Measurement System (PROMIS) will be used to measure participants' self-report of symptoms, function, and health-related quality of life in the domains of physical, mental and social health.~All subjects will undergo a two-step euglycemic insulin clamp and indirect calorimetry.~Only older obese participants will continue to the randomization to likestyle intervention, senolytic agents or placebo.

Single Nuclei RNA-sequencing to Map Adipose Cellular Populations and Senescent Cells in Older Subjects

Obesity, Healthy Lifestyle

* Other: Lifestyle Intervention * Drug: Dasatinib 100 MG * Drug: Quercetin 1000mg * Drug: Placebo * Procedure: Abdominal adipose tissue biopsy

Inclusion Criteria:~Both Sexes~Age: younger lean group 18-30 years with BMI 18.5-24.9 kg/m2; older lean group ≥ 65 years with BMI~All races and ethnic groups~Community dwelling~Sedentary (≤1.5 h of exercise per week)~Nondiabetic (fasting plasma glucose < 126 mg/dl, 2-h glucose during oral glucose tolerance test (OGTT) < 140mg/dl, and A1c < 6.5%~For all female participants who are women of childbearing potential (WOCBP), who are not pregnant or breast feeding, at least one of the following conditions must apply:~A documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy Use of a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency (implantable progesterone-only hormone contraception, intrauterine hormone releasing system, bilateral tubal occlusion, vasectomized partner) during the intervention period of the study and for at least 30 days after the last dose of study intervention to eliminate any reproductive safety risk of the study drug.~Use of a contraceptive method that is highly effective (with a failure rate of <1% per year), with high user dependency, (oral/intravaginal/injectable combined estrogen and progesterone contraception, oral/injectable progesterone only hormone contraception, sexual abstinence) during the intervention period and for at least 30 days after the last dose of study intervention to eliminate any reproductive safety risk of the study drug. In addition to the highly effective methods: male or female condom with or without spermicide; cervical cap, diaphragm, or sponge with spermicide; a combination of male condom with either cervical cap, diaphragm, or sponge with spermicide.~ECG value after 10 minutes of resting in the supine position in the following ranges:~120ms<PR<220ms: QRS<120ms; QTc<430ms for males and QTc<450ms for females and normal ECG tracing, unless the investigator considers the ECG abnormality to be not clinically relevant.~Exclusion Criteria:~Diabetes, clinically diagnosed or HbA1c > 6.5% and/or fasting plasma glucose > 126 mg/dl and/or use of anti-diabetic medications.~Participating in > 1.5 h of structured exercise/week~Unstable weight (>3% change in last 3 months)~Neurological, musculoskeletal, or other conditions that may limit subject's ability to complete study physical assessment and training~Active autoimmune/inflammatory disease including: rheumatoid arthritis, multiple sclerosis, systemic lupus erythematous, inflammatory bowel disease~Laboratory parameters outside the normal range:~impaired kidney function (eGFR < 30ml/min/1.73m² as calculated by the CKD-EPI equation);~impaired liver function (AST or ALT level > 2 times upper limit of normal (ULN);~total Bilirubin level > 1.5 times ULN;~TSH > 1.5 times ULN or < lower limit of normal (LLN);~Hemoglobin <10.0 g/dl; Platelets <125,000 cell/mm³;~Platelets < 125,000 cell/mm³~Prothrombin time (PT) > 1.0 times ULN~Partial prothrombin time (PTT) > 1.0 times ULN.~Active gastrointestinal disease; coagulopathy; GI bleed within 6 months~Clinically significant heart disease (e.g. NYH Classification >II; ischemia)~Peripheral vascular disease (claudication)~QTc prolongation >45 msec~Use of anti-arrhythmic medications known to cause QTc prolongation, anti-platelet or anti-coagulant medication (see section 5.3)~Use of quinolone antibiotics or any other drugs that may prolong the QTc interval (see section 5.3)~Pulmonary disease (COPD), severe asthma or exercise-induced asthma~Recent systemic or pulmonary embolus~Uncontrolled blood pressure (systolic BP>170, diastolic BP>95 mmHg)~Smoking, alcohol use (history of regular alcohol consumption exceeding 7 drinks/week for female participants or 14 drinks/week for male participants. 1 drink = 5 ounces [150ml] of wine or 12 ounces [360ml] of beer or 1.5 ounces [45ml] of hard liquor) or recreational drug use~Pregnant or breastfeeding~Postmenopausal women new (within 6 months) to systemic hormone replacement therapy~Previous bariatric surgery~History of stroke with motor disability~Recent (3 years) treated cancer other than basal cell carcinoma~Acute or chronic infection~Medication that might interfere with metabolic studies (weight loss medication, systemic steroids, immunosuppressants) within 6 months (see section 5.3)~Potentially senolytic agents within the last 6 months: fisetin, quercetin, luteolin, dasatinib, piperlongumine, or navitoclax (see section 5.3)~History of allergy to dasatinib, quercetin and/or lidocaine.

18 Years

All

Accepts Healthy Volunteers

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: All participants will undergo cellular/molecular profiling and older obese participants will be randomized into 3 arms. Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Insulin sensitivity | Change in skeletal muscle insulin sensitivity | Week 4 and Week 15 | | Glucose tolerance | Measurement of change in glucose tolerance using a glucose tolerance test | Baseline to Week 14 |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Senescence-associated secretory phenotype (SASP) | Measurement of change of SASP in adipose tissue | Baseline to Week 16 |

Lifestyle intervention, Single RNA sequencing, Cell Senescence

Dasatinib, Quercetin, Antineoplastic Agents, Protein Kinase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antioxidants, Protective Agents, Physiological Effects of Drugs

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: Younger Lean Group<br>Participants will be aged 18-30 years and have a BMI of 18.5 - 24.9 kg/m2 | Procedure: Abdominal adipose tissue biopsy<br>* All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq<br>* Other names: Subcutaneous abdominal adipose tissue biopsy;| | Other: Older Lean Group<br>Participants will be over 65 years of age with a BMI of 18.5 to 24.9 kg/m2 | Procedure: Abdominal adipose tissue biopsy<br>* All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq<br>* Other names: Subcutaneous abdominal adipose tissue biopsy;| | Experimental: Older Obese Group<br>Participants will be over 65 years of age with a BMI of 30-39.9 kg/m2. | Other: Lifestyle Intervention<br>* Exercise: Subjects will undergo a combined aerobic and resistance exercise intervention. The investigators propose a multi-modal training program because they improve metabolic outcomes and adding resistance training reduces the risk of muscle loss during weight loss. Subjects will exercise in the gym for three sessions per week for 10 weeks under supervision of an exercise physiologist. On each session, aerobic exercise will be followed by resistance exercise.~Diet: The aim of the dietary intervention is to reduce caloric intake sufficient to result in 8-10% weight loss, while incorporating behavioral and dietary strategies to maximize adherence and to minimize risk of muscle and bone loss. Subjects will attend small-group sessions led by a dietitian for changing their dietary composition to follow American Heart Association (AHA)/American College of Cardiology (ACC) guidelines.<br>* Other names: Exercise and Diet;Drug: Dasatinib 100 MG<br>* 100 mg of dasatinib (D) daily for 3 consecutive days plus quercetin (Q) for the same 3 consecutive days, followed by a 25-day (+/- 2 day) no-drug period to complete a single round. This will be repeated twice more until completing 3 rounds total in approximately 10 consecutive weeks.<br>* Other names: Sprycell;Drug: Quercetin 1000mg<br>* Quercetin (Q) (4) 250 mg capsules daily (total 1000 mg daily) plus dasatinib (D) same 3 consecutive days, followed by a 25-day (+/- 2 day) no-drug period to complete a single round. This will be repeated twice more until completing 3 rounds total in approximately 10 consecutive weeks.<br>Drug: Placebo<br>* Subjects will receive a placebo (methylcellulose) to provide a similar mass, number of tablets/ capsules, and frequency as the senolytic arm.<br>* Other names: Placebo capsule;Procedure: Abdominal adipose tissue biopsy<br>* All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq<br>* Other names: Subcutaneous abdominal adipose tissue biopsy;|

Single Nuclei RNA-seq to Map Adipose Cellular Populations and Senescent Cells in Older Subjects Study Overview ================= Brief Summary ----------------- All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq and metabolic/physiological assessments (insulin sensitivity, glucose tolerance, and β-cell function). Older obese participants will be randomized into three arms: lifestyle intervention (n=24), senolytics (n=24), or placebo (n=24). Detailed Description ----------------- All participants after consent and enrollment will undergo adipose tissue single nuclei RNA sequencing and metabolic phenotyping. Subjects will undergo glucose tolerance testing to document glucose tolerance status. Each subject will be provided an accelerometer to be worn on their dominant wrist for 7 days for assessment of habitual activity. A dietitian will teach them to utilize the SmartIntake3 smartphone food picture application (app) for a 7-day food record. The app will be used to record amount of each meal consumed in order to determine daily food and beverage and supplement intake and quantity for dietary composition analysis. DEXA analysis will be performed to measure lean and fat body mass. Subjects will undergo evaluation of physical function/performance, including the Short Physical Performance Battery (SPPB) and VO2 peak testing for assessment of aerobic capacity. The SPPB will be done in older adults only. The NIH Patient-Reported Outcomes Measurement System (PROMIS) will be used to measure participants' self-report of symptoms, function, and health-related quality of life in the domains of physical, mental and social health. All subjects will undergo a two-step euglycemic insulin clamp and indirect calorimetry. Only older obese participants will continue to the randomization to likestyle intervention, senolytic agents or placebo. Official Title ----------------- Single Nuclei RNA-sequencing to Map Adipose Cellular Populations and Senescent Cells in Older Subjects Conditions ----------------- Obesity, Healthy Lifestyle Intervention / Treatment ----------------- * Other: Lifestyle Intervention * Drug: Dasatinib 100 MG * Drug: Quercetin 1000mg * Drug: Placebo * Procedure: Abdominal adipose tissue biopsy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Both Sexes Age: younger lean group 18-30 years with BMI 18.5-24.9 kg/m2; older lean group ≥ 65 years with BMI All races and ethnic groups Community dwelling Sedentary (≤1.5 h of exercise per week) Nondiabetic (fasting plasma glucose < 126 mg/dl, 2-h glucose during oral glucose tolerance test (OGTT) < 140mg/dl, and A1c < 6.5% For all female participants who are women of childbearing potential (WOCBP), who are not pregnant or breast feeding, at least one of the following conditions must apply: A documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy Use of a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency (implantable progesterone-only hormone contraception, intrauterine hormone releasing system, bilateral tubal occlusion, vasectomized partner) during the intervention period of the study and for at least 30 days after the last dose of study intervention to eliminate any reproductive safety risk of the study drug. Use of a contraceptive method that is highly effective (with a failure rate of <1% per year), with high user dependency, (oral/intravaginal/injectable combined estrogen and progesterone contraception, oral/injectable progesterone only hormone contraception, sexual abstinence) during the intervention period and for at least 30 days after the last dose of study intervention to eliminate any reproductive safety risk of the study drug. In addition to the highly effective methods: male or female condom with or without spermicide; cervical cap, diaphragm, or sponge with spermicide; a combination of male condom with either cervical cap, diaphragm, or sponge with spermicide. ECG value after 10 minutes of resting in the supine position in the following ranges: 120ms<PR<220ms: QRS<120ms; QTc<430ms for males and QTc<450ms for females and normal ECG tracing, unless the investigator considers the ECG abnormality to be not clinically relevant. Exclusion Criteria: Diabetes, clinically diagnosed or HbA1c > 6.5% and/or fasting plasma glucose > 126 mg/dl and/or use of anti-diabetic medications. Participating in > 1.5 h of structured exercise/week Unstable weight (>3% change in last 3 months) Neurological, musculoskeletal, or other conditions that may limit subject's ability to complete study physical assessment and training Active autoimmune/inflammatory disease including: rheumatoid arthritis, multiple sclerosis, systemic lupus erythematous, inflammatory bowel disease Laboratory parameters outside the normal range: impaired kidney function (eGFR < 30ml/min/1.73m² as calculated by the CKD-EPI equation); impaired liver function (AST or ALT level > 2 times upper limit of normal (ULN); total Bilirubin level > 1.5 times ULN; TSH > 1.5 times ULN or < lower limit of normal (LLN); Hemoglobin <10.0 g/dl; Platelets <125,000 cell/mm³; Platelets < 125,000 cell/mm³ Prothrombin time (PT) > 1.0 times ULN Partial prothrombin time (PTT) > 1.0 times ULN. Active gastrointestinal disease; coagulopathy; GI bleed within 6 months Clinically significant heart disease (e.g. NYH Classification >II; ischemia) Peripheral vascular disease (claudication) QTc prolongation >45 msec Use of anti-arrhythmic medications known to cause QTc prolongation, anti-platelet or anti-coagulant medication (see section 5.3) Use of quinolone antibiotics or any other drugs that may prolong the QTc interval (see section 5.3) Pulmonary disease (COPD), severe asthma or exercise-induced asthma Recent systemic or pulmonary embolus Uncontrolled blood pressure (systolic BP>170, diastolic BP>95 mmHg) Smoking, alcohol use (history of regular alcohol consumption exceeding 7 drinks/week for female participants or 14 drinks/week for male participants. 1 drink = 5 ounces [150ml] of wine or 12 ounces [360ml] of beer or 1.5 ounces [45ml] of hard liquor) or recreational drug use Pregnant or breastfeeding Postmenopausal women new (within 6 months) to systemic hormone replacement therapy Previous bariatric surgery History of stroke with motor disability Recent (3 years) treated cancer other than basal cell carcinoma Acute or chronic infection Medication that might interfere with metabolic studies (weight loss medication, systemic steroids, immunosuppressants) within 6 months (see section 5.3) Potentially senolytic agents within the last 6 months: fisetin, quercetin, luteolin, dasatinib, piperlongumine, or navitoclax (see section 5.3) History of allergy to dasatinib, quercetin and/or lidocaine. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: All participants will undergo cellular/molecular profiling and older obese participants will be randomized into 3 arms. Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: Younger Lean Group<br>Participants will be aged 18-30 years and have a BMI of 18.5 - 24.9 kg/m2 | Procedure: Abdominal adipose tissue biopsy<br>* All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq<br>* Other names: Subcutaneous abdominal adipose tissue biopsy;| | Other: Older Lean Group<br>Participants will be over 65 years of age with a BMI of 18.5 to 24.9 kg/m2 | Procedure: Abdominal adipose tissue biopsy<br>* All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq<br>* Other names: Subcutaneous abdominal adipose tissue biopsy;| | Experimental: Older Obese Group<br>Participants will be over 65 years of age with a BMI of 30-39.9 kg/m2. | Other: Lifestyle Intervention<br>* Exercise: Subjects will undergo a combined aerobic and resistance exercise intervention. The investigators propose a multi-modal training program because they improve metabolic outcomes and adding resistance training reduces the risk of muscle loss during weight loss. Subjects will exercise in the gym for three sessions per week for 10 weeks under supervision of an exercise physiologist. On each session, aerobic exercise will be followed by resistance exercise. Diet: The aim of the dietary intervention is to reduce caloric intake sufficient to result in 8-10% weight loss, while incorporating behavioral and dietary strategies to maximize adherence and to minimize risk of muscle and bone loss. Subjects will attend small-group sessions led by a dietitian for changing their dietary composition to follow American Heart Association (AHA)/American College of Cardiology (ACC) guidelines.<br>* Other names: Exercise and Diet;Drug: Dasatinib 100 MG<br>* 100 mg of dasatinib (D) daily for 3 consecutive days plus quercetin (Q) for the same 3 consecutive days, followed by a 25-day (+/- 2 day) no-drug period to complete a single round. This will be repeated twice more until completing 3 rounds total in approximately 10 consecutive weeks.<br>* Other names: Sprycell;Drug: Quercetin 1000mg<br>* Quercetin (Q) (4) 250 mg capsules daily (total 1000 mg daily) plus dasatinib (D) same 3 consecutive days, followed by a 25-day (+/- 2 day) no-drug period to complete a single round. This will be repeated twice more until completing 3 rounds total in approximately 10 consecutive weeks.<br>Drug: Placebo<br>* Subjects will receive a placebo (methylcellulose) to provide a similar mass, number of tablets/ capsules, and frequency as the senolytic arm.<br>* Other names: Placebo capsule;Procedure: Abdominal adipose tissue biopsy<br>* All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq<br>* Other names: Subcutaneous abdominal adipose tissue biopsy;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Insulin sensitivity | Change in skeletal muscle insulin sensitivity | Week 4 and Week 15 | | Glucose tolerance | Measurement of change in glucose tolerance using a glucose tolerance test | Baseline to Week 14 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Senescence-associated secretory phenotype (SASP) | Measurement of change of SASP in adipose tissue | Baseline to Week 16 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Lifestyle intervention, Single RNA sequencing, Cell Senescence

NCT02876107

Carboplatin and Paclitaxel With or Without Panitumumab in Treating Patients With Invasive Triple Negative Breast Cancer

This randomized phase II trial studies how well carboplatin and paclitaxel with or without panitumumab work in treating patients with invasive triple negative breast cancer. Drugs used in the chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping the them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Giving carboplatin and paclitaxel with or without panitumumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PRIMARY OBJECTIVES:~I. To determine the pathologic complete response (pCR) rate in patients with primary triple-receptor negative (estrogen receptor [ER]-negative, progesterone receptor [PgR]-negative, and human epidermal growth factor receptor 2 [HER2]-negative) inflammatory breast cancer (TN-IBC) by using a combination of panitumumab, carboplatin, and paclitaxel (PaCT) in comparison with carboplatin and paclitaxel (CT) followed by adriamycin and cyclophosphamide (AC) in a neoadjuvant setting.~SECONDARY OBJECTIVES:~I. To determine the disease-free survival (DFS) rates produced by either arm of trial combination treatment.~II. To determine the overall survival (OS) rates produced by either arm of trial combination treatment.~III. To determine the safety and tolerability of both arms of trial combination treatment.~EXPLORATORY OBJECTIVES:~I. To determine whether the pCR rate positively correlates with reduced nodal expression status.~II. To determine whether the pCR rate inversely correlates with arginine methylation status of epidermal growth factor receptor (EGFR).~III. To identify molecular biomarkers predictive of the pCR rate by analysis of multiplexed immunohistochemical (IHC) staining.~IV. To identify molecular biomarkers predictive of the pCR rate by genomic and proteomic analysis.~V. To determine whether the inhibition of the EGFR pathway downregulates the COX-2 pathway and mesenchymal marker.~OUTLINE: Patients are randomized into 1 of 2 groups.~GROUP A: Patients receive panitumumab intravenously (IV) over 1 hour on day 1 of cycle 0 and over 30 minutes on days 1, 8, and 15 of cycles 1-4. Patients also receive paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1 of cycles 1-4. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity.~GROUP B: Patients receive paclitaxel, carboplatin, doxorubicin, and cyclophosphamide as in Group A. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity.~After completion of study treatment, patients are followed up at 1 month and then annually for at least 5 years.

A Randomized Phase II Study of Neoadjuvant Carboplatin/Paclitaxel (CT) Versus Panitumumab/Carboplatin/Paclitaxel (PaCT) Followed by Anthracycline-Containing Regimen for Newly Diagnosed Primary Triple-Negative Inflammatory Breast Cancer

Peau d'Orange, Breast Carcinoma, Breast Lump, Edema, Erythema, Estrogen Receptor Negative, HER2/Neu Negative, Inflammatory Breast Carcinoma, Invasive Breast Carcinoma, Progesterone Receptor Negative, Triple-Negative Breast Carcinoma

* Drug: Carboplatin * Other: Laboratory Biomarker Analysis * Drug: Paclitaxel * Biological: Panitumumab

Inclusion Criteria:~Patients must have histological confirmation of breast carcinoma~Patients must have invasive breast cancer (IBC), confirmed according to international consensus criteria:~Onset: Rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm breast, with or without an underlying breast mass~Duration: History of such findings no more than 6 months~Extent: Erythema occupying at least 1/3 of whole breast~Pathology: Pathologic confirmation of invasive carcinoma~Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1~Patients must have negative HER2 expression on immunohistochemistry (IHC) (defined as 0 or 1+) or fluorescence in situ hybridization (FISH) analysis; if HER2 is 2+, negative HER2 expression must be confirmed by FISH (HER2/cep17 ration < 2, and/or copy number less than 6); ER and PgR expression should be less than 10%~Patients have left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition scan (MUGA) or echocardiogram before study randomization~Absolute neutrophil count (ANC) >= 1.5 x 10^9/L~Platelet count >= 100 x 10^9/L~Hemoglobin >= 9.0 g/dL~Aspartate aminotransferase (AST) =< 3.0 x upper limit of normal (ULN)~Alanine aminotransferase (ALT) =< 3.0 x ULN~Alkaline phosphatase (ALP) =< 2.5 x ULN~Total bilirubin =< 1.5 x ULN~Creatinine (Cr) =< 1.5 mg/dL x ULN~Creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockroft-Gault~Patients have the ability and willingness to sign written informed consent~Patients of childbearing potential (women who are postmenopausal for < 1 year, not surgically sterilized, or not abstinent), have a negative urine pregnancy test, and agree to the consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile before the female subject's entry into the study and is the sole sexual partner for that female subject; intrauterine device, oral contraception, or barrier methods, including diaphragm or condom with a spermicide~Exclusion Criteria:~Stage IV disease, if the metastatic sites are not amendable for local therapy (i.e. radiation and/or surgery), and are not candidates for breast surgery will not be eligible~History of radiotherapy for current breast cancer diagnosis~History of recent malignancies < 5 years (except for cured non-melanomatous skin cancer or cured cervical carcinoma in situ)~Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection~History of extensive interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or any evidence of extensive interstitial lung disease on baseline chest computed tomography (CT) scan~Other known other significant medical or psychiatric condition that would make assessment of toxicity or efficacy difficult~Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements~Patients with a peripheral neuropathy > grade 1~Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina, or cerebrovascular accident (CVA) within 6 months of protocol registration~Patients have a history of prior therapy with carboplatin~Patients have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2~Patients have had prior radiotherapy for primary breast carcinoma or axillary lymph nodes~Patients have history of diagnosed interstitial lung disease

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Complete pathologic response | Will be estimated for each treatment arm with exact 95% confidence intervals. A Chi-square test or Fisher's exact test will be used to compare the differences in complete pathologic response rate between the two treatment arms. A logistic regression model will be used to assess the differences in complete pathologic response between the two treatment arms, adjusting for other covariates as appropriate. The analysis will be based on the modified intent-to-treat population. | At the time of surgery, assessed up to 5 years |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Disease free survival | The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes. | Up to 5 years | | Overall survival | The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes. | Up to 5 years | | Incidence of adverse events | Descriptive statistics will be used. | Up to 5 years |

Paclitaxel, Carboplatin, Albumin-Bound Paclitaxel, Panitumumab, Antineoplastic Agents, Immunological, Antibodies, Immunoglobulins, Antibodies, Monoclonal, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action, Immunologic Factors, Physiological Effects of Drugs

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Group A (panitumumab, paclitaxel, carboplatin)<br>Patients receive panitumumab IV over 1 hour on day 1 of cycle 0 and over 30 minutes on days 1, 8, and 15 of cycles 1-4. Patients also receive paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1 of cycles 1-4. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity. | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Paclitaxel<br>* Given IV<br>* Other names: Taxol Konzentrat;Biological: Panitumumab<br>* Given IV<br>* Other names: Vectibix;| | Experimental: Group B (paclitaxel, carboplatin)<br>Patients receive paclitaxel, carboplatin, doxorubicin, and cyclophosphamide as in Group A. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity. | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Paclitaxel<br>* Given IV<br>* Other names: Taxol Konzentrat;|

Carboplatin and Paclitaxel With or Without Panitumumab in Treating Patients With Invasive Triple Negative Breast Cancer Study Overview ================= Brief Summary ----------------- This randomized phase II trial studies how well carboplatin and paclitaxel with or without panitumumab work in treating patients with invasive triple negative breast cancer. Drugs used in the chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping the them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Giving carboplatin and paclitaxel with or without panitumumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Detailed Description ----------------- PRIMARY OBJECTIVES: I. To determine the pathologic complete response (pCR) rate in patients with primary triple-receptor negative (estrogen receptor [ER]-negative, progesterone receptor [PgR]-negative, and human epidermal growth factor receptor 2 [HER2]-negative) inflammatory breast cancer (TN-IBC) by using a combination of panitumumab, carboplatin, and paclitaxel (PaCT) in comparison with carboplatin and paclitaxel (CT) followed by adriamycin and cyclophosphamide (AC) in a neoadjuvant setting. SECONDARY OBJECTIVES: I. To determine the disease-free survival (DFS) rates produced by either arm of trial combination treatment. II. To determine the overall survival (OS) rates produced by either arm of trial combination treatment. III. To determine the safety and tolerability of both arms of trial combination treatment. EXPLORATORY OBJECTIVES: I. To determine whether the pCR rate positively correlates with reduced nodal expression status. II. To determine whether the pCR rate inversely correlates with arginine methylation status of epidermal growth factor receptor (EGFR). III. To identify molecular biomarkers predictive of the pCR rate by analysis of multiplexed immunohistochemical (IHC) staining. IV. To identify molecular biomarkers predictive of the pCR rate by genomic and proteomic analysis. V. To determine whether the inhibition of the EGFR pathway downregulates the COX-2 pathway and mesenchymal marker. OUTLINE: Patients are randomized into 1 of 2 groups. GROUP A: Patients receive panitumumab intravenously (IV) over 1 hour on day 1 of cycle 0 and over 30 minutes on days 1, 8, and 15 of cycles 1-4. Patients also receive paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1 of cycles 1-4. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity. GROUP B: Patients receive paclitaxel, carboplatin, doxorubicin, and cyclophosphamide as in Group A. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity. After completion of study treatment, patients are followed up at 1 month and then annually for at least 5 years. Official Title ----------------- A Randomized Phase II Study of Neoadjuvant Carboplatin/Paclitaxel (CT) Versus Panitumumab/Carboplatin/Paclitaxel (PaCT) Followed by Anthracycline-Containing Regimen for Newly Diagnosed Primary Triple-Negative Inflammatory Breast Cancer Conditions ----------------- Peau d'Orange, Breast Carcinoma, Breast Lump, Edema, Erythema, Estrogen Receptor Negative, HER2/Neu Negative, Inflammatory Breast Carcinoma, Invasive Breast Carcinoma, Progesterone Receptor Negative, Triple-Negative Breast Carcinoma Intervention / Treatment ----------------- * Drug: Carboplatin * Other: Laboratory Biomarker Analysis * Drug: Paclitaxel * Biological: Panitumumab Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients must have histological confirmation of breast carcinoma Patients must have invasive breast cancer (IBC), confirmed according to international consensus criteria: Onset: Rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm breast, with or without an underlying breast mass Duration: History of such findings no more than 6 months Extent: Erythema occupying at least 1/3 of whole breast Pathology: Pathologic confirmation of invasive carcinoma Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Patients must have negative HER2 expression on immunohistochemistry (IHC) (defined as 0 or 1+) or fluorescence in situ hybridization (FISH) analysis; if HER2 is 2+, negative HER2 expression must be confirmed by FISH (HER2/cep17 ration < 2, and/or copy number less than 6); ER and PgR expression should be less than 10% Patients have left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition scan (MUGA) or echocardiogram before study randomization Absolute neutrophil count (ANC) >= 1.5 x 10^9/L Platelet count >= 100 x 10^9/L Hemoglobin >= 9.0 g/dL Aspartate aminotransferase (AST) =< 3.0 x upper limit of normal (ULN) Alanine aminotransferase (ALT) =< 3.0 x ULN Alkaline phosphatase (ALP) =< 2.5 x ULN Total bilirubin =< 1.5 x ULN Creatinine (Cr) =< 1.5 mg/dL x ULN Creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockroft-Gault Patients have the ability and willingness to sign written informed consent Patients of childbearing potential (women who are postmenopausal for < 1 year, not surgically sterilized, or not abstinent), have a negative urine pregnancy test, and agree to the consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile before the female subject's entry into the study and is the sole sexual partner for that female subject; intrauterine device, oral contraception, or barrier methods, including diaphragm or condom with a spermicide Exclusion Criteria: Stage IV disease, if the metastatic sites are not amendable for local therapy (i.e. radiation and/or surgery), and are not candidates for breast surgery will not be eligible History of radiotherapy for current breast cancer diagnosis History of recent malignancies < 5 years (except for cured non-melanomatous skin cancer or cured cervical carcinoma in situ) Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection History of extensive interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or any evidence of extensive interstitial lung disease on baseline chest computed tomography (CT) scan Other known other significant medical or psychiatric condition that would make assessment of toxicity or efficacy difficult Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients with a peripheral neuropathy > grade 1 Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina, or cerebrovascular accident (CVA) within 6 months of protocol registration Patients have a history of prior therapy with carboplatin Patients have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2 Patients have had prior radiotherapy for primary breast carcinoma or axillary lymph nodes Patients have history of diagnosed interstitial lung disease Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Group A (panitumumab, paclitaxel, carboplatin)<br>Patients receive panitumumab IV over 1 hour on day 1 of cycle 0 and over 30 minutes on days 1, 8, and 15 of cycles 1-4. Patients also receive paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1 of cycles 1-4. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity. | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Paclitaxel<br>* Given IV<br>* Other names: Taxol Konzentrat;Biological: Panitumumab<br>* Given IV<br>* Other names: Vectibix;| | Experimental: Group B (paclitaxel, carboplatin)<br>Patients receive paclitaxel, carboplatin, doxorubicin, and cyclophosphamide as in Group A. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity. | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Paclitaxel<br>* Given IV<br>* Other names: Taxol Konzentrat;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Complete pathologic response | Will be estimated for each treatment arm with exact 95% confidence intervals. A Chi-square test or Fisher's exact test will be used to compare the differences in complete pathologic response rate between the two treatment arms. A logistic regression model will be used to assess the differences in complete pathologic response between the two treatment arms, adjusting for other covariates as appropriate. The analysis will be based on the modified intent-to-treat population. | At the time of surgery, assessed up to 5 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Disease free survival | The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes. | Up to 5 years | | Overall survival | The method of Kaplan-Meier method will be used to estimate the time-to-event outcomes. | Up to 5 years | | Incidence of adverse events | Descriptive statistics will be used. | Up to 5 years |

NCT01893177

Re-licensing Study to Assess Inflexal V Formulated With WHO Recommended Influenza Strains (2013-14)

The study is to assess whether the influenza vaccine Inflexal V for season 2013/2014 fulfills the EMA requirements for re-registration of influenza vaccines.

Open, Non-randomized Trial to Assess the Immunogenicity and Safety of the 2013/2014-season Virosomal Subunit Influenza Vaccine in Elderly and Young Subjects According to EMA Regulations

Influenza

* Biological: Inflexal V

Inclusion Criteria:~Healthy female and male adults aged ≥18 on Day 1~Written informed consent~Female subjects of childbearing potential using and willing to continue using an acceptable method of contraception unless surgically sterilized/hysterectomized or post-menopausal for more than 2 years~Exclusion Criteria:~Acute exacerbation of bronchopulmonary infection (cough, sputum, lung findings) or other acute disease~Acute febrile illness (≥38.0 °C)~Prior vaccination with an influenza vaccine in the past 330 days~Known hypersensitivity to any vaccine component~Previous history of a serious adverse reaction to influenza vaccine~History of egg protein allergy or severe atopy~Known blood coagulation disorder~Chronic (longer than 14 days) administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of the study vaccine, including oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent (inhaled or topical steroids are allowed)~Known immunodeficiency (incl. leukemia, HIV seropositivity), cancer~Investigational medicinal product received in the past 3 months (90 days)~Treatment with immunoglobulins or blood transfusion(s) received in the past 3 months (90 days)~Pregnancy or lactation~Participation in another clinical trial~Employee at the investigational site, or relative of the investigator~Subjects who in the view of the investigator will not comply with study procedures and/or visit requirements as per protocol

18 Years

All

Accepts Healthy Volunteers

Primary Purpose: Prevention Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percentage of subjects with seroconversion, seroprotection, and fold increase in geometric mean titer (GMT) | Immunogenicity variables are analyzed according to the EMA re-licensing criteria; at least one of the criteria has to be fulfilled for each vaccine strain:~Seroconversion rate at Day 22 has to be >40% of subjects aged ≥18 to ≤60 years and >30% of subjects aged >60 years, or~Seroprotection rate at Day 22 has to be >70% of subjects aged ≥18 to ≤60 years and >60% of subjects aged >60 years, or~GMT-fold increase at Day 22 compared to baseline: a >2.5-fold increase has to be reached in subjects aged ≥18 to ≤60 years and a >2.0-fold increase has to be reached in subjects aged >60 years | Day 22 +/- 2 days |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of solicited local adverse events | | Days 1 to 4 inclusive | | Incidence of solicited systemic adverse events | | Days 1 to 4 inclusive | | Incidence of unsolicited adverse events | | Days 1 to 22 inclusive |

Influenza, Virus, Vaccination, Inflexal V

Vaccines, Immunologic Factors, Physiological Effects of Drugs

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Elderly subjects aged over 60 years<br> | Biological: Inflexal V<br>* Intramuscular administration (M. deltoideus) of a single dose of 0.5 mL Inflexal V<br>* Other names: • 15 µg HA antigen of B/Massachusetts/2/2012-like virus;| | Experimental: Adults from 18 to 60 years old inclusive<br> | Biological: Inflexal V<br>* Intramuscular administration (M. deltoideus) of a single dose of 0.5 mL Inflexal V<br>* Other names: • 15 µg HA antigen of B/Massachusetts/2/2012-like virus;|

Re-licensing Study to Assess Inflexal V Formulated With WHO Recommended Influenza Strains (2013-14) Study Overview ================= Brief Summary ----------------- The study is to assess whether the influenza vaccine Inflexal V for season 2013/2014 fulfills the EMA requirements for re-registration of influenza vaccines. Official Title ----------------- Open, Non-randomized Trial to Assess the Immunogenicity and Safety of the 2013/2014-season Virosomal Subunit Influenza Vaccine in Elderly and Young Subjects According to EMA Regulations Conditions ----------------- Influenza Intervention / Treatment ----------------- * Biological: Inflexal V Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Healthy female and male adults aged ≥18 on Day 1 Written informed consent Female subjects of childbearing potential using and willing to continue using an acceptable method of contraception unless surgically sterilized/hysterectomized or post-menopausal for more than 2 years Exclusion Criteria: Acute exacerbation of bronchopulmonary infection (cough, sputum, lung findings) or other acute disease Acute febrile illness (≥38.0 °C) Prior vaccination with an influenza vaccine in the past 330 days Known hypersensitivity to any vaccine component Previous history of a serious adverse reaction to influenza vaccine History of egg protein allergy or severe atopy Known blood coagulation disorder Chronic (longer than 14 days) administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of the study vaccine, including oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent (inhaled or topical steroids are allowed) Known immunodeficiency (incl. leukemia, HIV seropositivity), cancer Investigational medicinal product received in the past 3 months (90 days) Treatment with immunoglobulins or blood transfusion(s) received in the past 3 months (90 days) Pregnancy or lactation Participation in another clinical trial Employee at the investigational site, or relative of the investigator Subjects who in the view of the investigator will not comply with study procedures and/or visit requirements as per protocol Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Elderly subjects aged over 60 years<br> | Biological: Inflexal V<br>* Intramuscular administration (M. deltoideus) of a single dose of 0.5 mL Inflexal V<br>* Other names: • 15 µg HA antigen of B/Massachusetts/2/2012-like virus;| | Experimental: Adults from 18 to 60 years old inclusive<br> | Biological: Inflexal V<br>* Intramuscular administration (M. deltoideus) of a single dose of 0.5 mL Inflexal V<br>* Other names: • 15 µg HA antigen of B/Massachusetts/2/2012-like virus;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percentage of subjects with seroconversion, seroprotection, and fold increase in geometric mean titer (GMT) | Immunogenicity variables are analyzed according to the EMA re-licensing criteria; at least one of the criteria has to be fulfilled for each vaccine strain: Seroconversion rate at Day 22 has to be >40% of subjects aged ≥18 to ≤60 years and >30% of subjects aged >60 years, or Seroprotection rate at Day 22 has to be >70% of subjects aged ≥18 to ≤60 years and >60% of subjects aged >60 years, or GMT-fold increase at Day 22 compared to baseline: a >2.5-fold increase has to be reached in subjects aged ≥18 to ≤60 years and a >2.0-fold increase has to be reached in subjects aged >60 years | Day 22 +/- 2 days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of solicited local adverse events | | Days 1 to 4 inclusive | | Incidence of solicited systemic adverse events | | Days 1 to 4 inclusive | | Incidence of unsolicited adverse events | | Days 1 to 22 inclusive | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Influenza, Virus, Vaccination, Inflexal V

NCT02615314

Clinical Aspects of Patients With Benign Paroxysmal Positional Vertigo (BPPV) and Migraine

The aim of this study is to analyze the clinical aspects of patients with BPPV associated with migraine. It is our purpose to clarify weather migraine is a risk factor for BPPV if the clinical aspect and the therapeutic outcome is different.

Two hundred and sixty-three patients with BPPV were enrolled in this retrospective study. All patients' charts were reviewed by independent observer. The type of BPPV and associated problems were noted. Patients with migraine were investigated in terms of age, gender, symptoms, affected side and the cure rate. Their data were compared with those having no migraine. Mean values and standard deviations (± SD) were calculated. One way ANOVA test was used for the analysis. Significance was set at p < 0.005.

Clinical Aspects of Patients With Benign Paroxysmal Positional Vertigo (BPPV) and Migraine

Migraine, Positional Vertigo

* Procedure: Particle re-positioning maneuver

Inclusion Criteria:~Patients who had history of head-induced positional and brief vertigo and who have been confirmed by VNG were included~Exclusion Criteria:~Patients with balance problem other than BPPV,~Patients receiving any medication prior to therapeutic maneuver were excluded

10 Years

84 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of patients who had normal vestibular response to provocative tests 7 days after re-positioning maneuver | Every patient with BPPV who had positional nystagmus during Dix-Hallpike and head-roll provocative maneuvers will be treated with Epley or barbeque particle re-positioning maneuvers. Balance (positional nystagmus) of patients 7 days after re-positioning maneuvers will be assessed. | 7 days |

migraine, benign paroxysmal positional vertigo

Vertigo, Benign Paroxysmal Positional Vertigo, Migraine Disorders, Dizziness, Headache Disorders, Primary, Headache Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vestibular Diseases, Labyrinth Diseases, Ear Diseases, Otorhinolaryngologic Diseases, Neurologic Manifestations, Sensation Disorders

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | BPPV without migraine<br>Two hundred and sixty-three patients with BPPV (2009-2014), confirmed by videonystagmography (VNG), were enrolled in the study. Patients' charts were reviewed. They were grouped as those with or without migraine. Distribution of gender, age, duration of symptoms and affected side were reviewed. Two hundred and thirty-one patients with no migraine were identified. | Procedure: Particle re-positioning maneuver<br>* Patients with posterior canal BPPV (PC-BPPV) were treated with Epley maneuver. Patients with superior canal (SC-BPPV) were treated with Li or reverse Epley maneuver. Patients with lateral canal (LC) apogeotropic or geotropic nystagmus were treated with Barbeque, Semont's or Gufoni maneuvers. If geotropic or ageotropic type nystagmus is equal intensity on both sides. The involved side was determined according to the patient sense of disturbance or lying down positioning test. If the patient has involvement of both sides according to Dix-Hallpike maneuver. Therapeutic maneuver was applied to the more severe side. All patients were re-evaluated at maximum 7 days.<br>| | BPPV with migraine<br>Thirty-two patients (11.4%) with migraine were identified. Diagnosis and classification of migraine and its differentiation from other type of headaches was based on third edition of International classification of headache disorders (ICHD-III beta) by international headache society (IHS). All patients with migraine had migrainous headache with or without aura and they all were diagnosed in our institution and followed by our neurology staff. | Procedure: Particle re-positioning maneuver<br>* Patients with posterior canal BPPV (PC-BPPV) were treated with Epley maneuver. Patients with superior canal (SC-BPPV) were treated with Li or reverse Epley maneuver. Patients with lateral canal (LC) apogeotropic or geotropic nystagmus were treated with Barbeque, Semont's or Gufoni maneuvers. If geotropic or ageotropic type nystagmus is equal intensity on both sides. The involved side was determined according to the patient sense of disturbance or lying down positioning test. If the patient has involvement of both sides according to Dix-Hallpike maneuver. Therapeutic maneuver was applied to the more severe side. All patients were re-evaluated at maximum 7 days.<br>|

Clinical Aspects of Patients With Benign Paroxysmal Positional Vertigo (BPPV) and Migraine Study Overview ================= Brief Summary ----------------- The aim of this study is to analyze the clinical aspects of patients with BPPV associated with migraine. It is our purpose to clarify weather migraine is a risk factor for BPPV if the clinical aspect and the therapeutic outcome is different. Detailed Description ----------------- Two hundred and sixty-three patients with BPPV were enrolled in this retrospective study. All patients' charts were reviewed by independent observer. The type of BPPV and associated problems were noted. Patients with migraine were investigated in terms of age, gender, symptoms, affected side and the cure rate. Their data were compared with those having no migraine. Mean values and standard deviations (± SD) were calculated. One way ANOVA test was used for the analysis. Significance was set at p < 0.005. Official Title ----------------- Clinical Aspects of Patients With Benign Paroxysmal Positional Vertigo (BPPV) and Migraine Conditions ----------------- Migraine, Positional Vertigo Intervention / Treatment ----------------- * Procedure: Particle re-positioning maneuver Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients who had history of head-induced positional and brief vertigo and who have been confirmed by VNG were included Exclusion Criteria: Patients with balance problem other than BPPV, Patients receiving any medication prior to therapeutic maneuver were excluded Ages Eligible for Study ----------------- Minimum Age: 10 Years Maximum Age: 84 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | BPPV without migraine<br>Two hundred and sixty-three patients with BPPV (2009-2014), confirmed by videonystagmography (VNG), were enrolled in the study. Patients' charts were reviewed. They were grouped as those with or without migraine. Distribution of gender, age, duration of symptoms and affected side were reviewed. Two hundred and thirty-one patients with no migraine were identified. | Procedure: Particle re-positioning maneuver<br>* Patients with posterior canal BPPV (PC-BPPV) were treated with Epley maneuver. Patients with superior canal (SC-BPPV) were treated with Li or reverse Epley maneuver. Patients with lateral canal (LC) apogeotropic or geotropic nystagmus were treated with Barbeque, Semont's or Gufoni maneuvers. If geotropic or ageotropic type nystagmus is equal intensity on both sides. The involved side was determined according to the patient sense of disturbance or lying down positioning test. If the patient has involvement of both sides according to Dix-Hallpike maneuver. Therapeutic maneuver was applied to the more severe side. All patients were re-evaluated at maximum 7 days.<br>| | BPPV with migraine<br>Thirty-two patients (11.4%) with migraine were identified. Diagnosis and classification of migraine and its differentiation from other type of headaches was based on third edition of International classification of headache disorders (ICHD-III beta) by international headache society (IHS). All patients with migraine had migrainous headache with or without aura and they all were diagnosed in our institution and followed by our neurology staff. | Procedure: Particle re-positioning maneuver<br>* Patients with posterior canal BPPV (PC-BPPV) were treated with Epley maneuver. Patients with superior canal (SC-BPPV) were treated with Li or reverse Epley maneuver. Patients with lateral canal (LC) apogeotropic or geotropic nystagmus were treated with Barbeque, Semont's or Gufoni maneuvers. If geotropic or ageotropic type nystagmus is equal intensity on both sides. The involved side was determined according to the patient sense of disturbance or lying down positioning test. If the patient has involvement of both sides according to Dix-Hallpike maneuver. Therapeutic maneuver was applied to the more severe side. All patients were re-evaluated at maximum 7 days.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of patients who had normal vestibular response to provocative tests 7 days after re-positioning maneuver | Every patient with BPPV who had positional nystagmus during Dix-Hallpike and head-roll provocative maneuvers will be treated with Epley or barbeque particle re-positioning maneuvers. Balance (positional nystagmus) of patients 7 days after re-positioning maneuvers will be assessed. | 7 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- migraine, benign paroxysmal positional vertigo

NCT01505777

Exploratory Clinical Study to Evaluate the Optimal Dosage of Mosapride and Probiotics in Irritable Bowel Syndrome Without Predominant Diarrhea

The purpose of this study is to Evaluate the Optimal Dosage of Mosapride (Medirac) and Probitics in Irritable Bowel Syndrome Without Predominant Diarrhea.

Exploratory Clinical Study to Evaluate the Optimal Dosage of Mosapride and Probiotics in Irritable Bowel Syndrome Without Predominant Diarrhea: Double Blinded, Randomized, Placebo Drug Controlled, Parallel Designed, Multi-centered, Phase 2 Study

Irritable Bowel Syndrome Without Diarrhea

* Drug: Probiotics (Medirac) * Drug: Probiotics (Medirac) * Drug: Probiotics (Medirac) * Drug: Probiotics (Medirac) * Drug: Probiotics (Medirac) placebo/mosapride placebo

Inclusion Criteria:~Aged 18-75 years who satisfied RomeIII criteria for the diagnosis of IBS~Signed informed consent~Exclusion Criteria:~IBS-D~evidence of cathartic colon or history laxative abuse

18 Years

75 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline in patient's overall satisfaction relief over 4 weeks of treatment of IBS symptoms | | baseline and 4 week |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline in improvment of abdominal discomfort, pain, bloating, stool frequency, stool consistency, straining urgency over 4 weeks of treatment and during each week(4 weeks,6 weeks) | | baseline and 4 weeks, 6 weeks |

irritable bowel syndrome without predominant diarrhea, Probiotics(Medirac) 10/mosapride 10mg, Probiotics(Medirac) 15/mosapride 10mg, Probiotics(Medirac) 15/mosapride 15mg, Probiotics(Medirac) 30/mosapride 15mg, Probiotics(Medirac) placebo/mosapride placebo

Mosapride, Gastrointestinal Agents, Serotonin Receptor Agonists, Serotonin Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Probiotics(Medirac) 10/mosapride 10mg<br> | Drug: Probiotics (Medirac)<br>* 10/mosapride 10mg three times a day, P.O. 4week<br>| | Experimental: Probiotics(Medirac) 15/mosapride 10mg<br> | Drug: Probiotics (Medirac)<br>* 15/mosapride 10mg three times a day, P.O. 4week<br>| | Experimental: Probiotics(Medirac) 15/mosapride 15mg<br> | Drug: Probiotics (Medirac)<br>* 15/mosapride 15mg three times a day, P.O. 4week<br>| | Experimental: Probiotics(Medirac) 30/mosapride 15mg<br> | Drug: Probiotics (Medirac)<br>* 30/mosapride 15mg three times a day, P.O. 4week<br>| | Placebo Comparator: Probiotics(Medirac) placebo/mosapride placebo<br> | Drug: Probiotics (Medirac) placebo/mosapride placebo<br>* three times a day, P.O. 4week<br>|

Exploratory Clinical Study to Evaluate the Optimal Dosage of Mosapride and Probiotics in Irritable Bowel Syndrome Without Predominant Diarrhea Study Overview ================= Brief Summary ----------------- The purpose of this study is to Evaluate the Optimal Dosage of Mosapride (Medirac) and Probitics in Irritable Bowel Syndrome Without Predominant Diarrhea. Official Title ----------------- Exploratory Clinical Study to Evaluate the Optimal Dosage of Mosapride and Probiotics in Irritable Bowel Syndrome Without Predominant Diarrhea: Double Blinded, Randomized, Placebo Drug Controlled, Parallel Designed, Multi-centered, Phase 2 Study Conditions ----------------- Irritable Bowel Syndrome Without Diarrhea Intervention / Treatment ----------------- * Drug: Probiotics (Medirac) * Drug: Probiotics (Medirac) * Drug: Probiotics (Medirac) * Drug: Probiotics (Medirac) * Drug: Probiotics (Medirac) placebo/mosapride placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Aged 18-75 years who satisfied RomeIII criteria for the diagnosis of IBS Signed informed consent Exclusion Criteria: IBS-D evidence of cathartic colon or history laxative abuse Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Probiotics(Medirac) 10/mosapride 10mg<br> | Drug: Probiotics (Medirac)<br>* 10/mosapride 10mg three times a day, P.O. 4week<br>| | Experimental: Probiotics(Medirac) 15/mosapride 10mg<br> | Drug: Probiotics (Medirac)<br>* 15/mosapride 10mg three times a day, P.O. 4week<br>| | Experimental: Probiotics(Medirac) 15/mosapride 15mg<br> | Drug: Probiotics (Medirac)<br>* 15/mosapride 15mg three times a day, P.O. 4week<br>| | Experimental: Probiotics(Medirac) 30/mosapride 15mg<br> | Drug: Probiotics (Medirac)<br>* 30/mosapride 15mg three times a day, P.O. 4week<br>| | Placebo Comparator: Probiotics(Medirac) placebo/mosapride placebo<br> | Drug: Probiotics (Medirac) placebo/mosapride placebo<br>* three times a day, P.O. 4week<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline in patient's overall satisfaction relief over 4 weeks of treatment of IBS symptoms | | baseline and 4 week | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline in improvment of abdominal discomfort, pain, bloating, stool frequency, stool consistency, straining urgency over 4 weeks of treatment and during each week(4 weeks,6 weeks) | | baseline and 4 weeks, 6 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- irritable bowel syndrome without predominant diarrhea, Probiotics(Medirac) 10/mosapride 10mg, Probiotics(Medirac) 15/mosapride 10mg, Probiotics(Medirac) 15/mosapride 15mg, Probiotics(Medirac) 30/mosapride 15mg, Probiotics(Medirac) placebo/mosapride placebo

NCT04720092

A Trial to Learn How a New Liquid Form of Rivaroxaban Behaves and How Safe it is Compared to the Current Tablet Form of Rivaroxaban in Healthy Male Participants

Researchers were looking for another way to treat people with a blood clot in their veins. Before a treatment can be approved for people to take, researchers do clinical trials to better understand its safety and how it behaves.~In this trial, the researchers learned how a new liquid form of rivaroxaban behaved compared to the tablet form in a small number of healthy participants. They also wanted to find out how safe it was. The trial included about 30 white men who were between the ages of 18 and 55. The participants also had a body mass index (BMI) between 18 and 29.9 kilograms per square meter (kg/m^2). BMI is a measurement that uses a person's height and weight to learn how much body fat they have.~All the participants in this trial took 10 milliliter of the new form of rivaroxaban (containing 1 milligram [mg] of rivaroxaban per milliliter). Later they also took 10 mg of the current tablet form of rivaroxaban. They took each form 1 time by mouth.~This trial was a crossover trial. In a crossover trial, all the participants take all of the treatments, but in a different order. In between the 2 treatments, there was a washout period of at least 7 days. This was done so that the first treatment could leave each participant's body before they took their next treatment.~While taking each treatment, the participants stayed at the trial site for 5 days. During this time, they did not eat food for at least 10 hours before and at least 4 hours after taking each treatment. After taking the last treatment, the participants had a final visit about 7 to 14 days later.~During the trial, the doctors took blood and urine samples. They also did physical examinations and checked the participants' heart health using an electrocardiogram (ECG). They asked the participants questions about how they were feeling and if they had any medical problems.

Single-dose, Open-label, Randomized, 2-way Crossover Bioequivalence Study of 10 mg Granules for Oral Suspension Rivaroxaban Versus 10 mg Tablets Rivaroxaban Under Fasted Condition in Healthy Subjects

Thromboembolic Disorders

* Drug: Rivaroxaban (Xarelto, BAY59-7939) * Drug: Rivaroxaban (Xarelto, BAY59-7939)

Inclusion Criteria:~The informed consent had to be signed before any study specific tests or procedures were done~Healthy male subjects~Age: 18 to 55 years (inclusive) at the screening examination/visit~Race: White~Body mass index (BMI): above/equal 18 and below/equal 29.9 kg/m^2~Ability to understand and follow instructions~Exclusion Criteria:~Pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal~Known or suspected liver disorders and bile secretion/flow~Subjects with thyroid disorders as evidenced by assessment of thyroid stimulating hormone (TSH) levels outside the normal reference range at screening~Personal or familial history of genetically muscular diseases~Known hypersensitivity to the study drugs (active substances or excipients of the preparations)~Known severe allergies e.g. allergies to more than 3 allergens, allergies affecting the lower respiratory tract- allergic asthma, allergies requiring therapy with corticosteroids, urticaria) or significant non-allergic drug reactions~Known disorders with increased bleeding risk (e.g., periodontosis, hemorrhoids, acute gastritis, peptic ulcer)~Known sensitivity to common causes of bleeding (e.g. nasal)~Clinically relevant findings in the electrocardiogram (ECG) such as a second- or third-degree atrioventricular (AV) block, prolongation of the QRS (QRS interval in ECG) complex over 120 msec or of the QTc-interval over 450 msec at the first screening visit~Presence or history of arrhythmic disturbances; or known congenital QT (QT interval in ECG) prolongation~Systolic blood pressure below 100 or above 140 mmHg~Diastolic blood pressure below 50 or above 90 mmHg~Heart rate below 50 or above 90 beats/ min

18 Years

55 Years

Male

Accepts Healthy Volunteers

Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Area under the concentration versus time curve from zero to infinity (AUC) of rivaroxaban in plasma after single dose | | Pre-dose up to 72 hours post-dose | | AUC from time zero to the last data point greater than (>) lower limit of quantification (LLOQ) (AUC[0-tlast]) of rivaroxaban in plasma after single dose | Area under the concentration versus time curve from zero to infinity (AUC) | Pre-dose up to 72 hours post-dose | | Maximum observed drug concentration (Cmax) of rivaroxaban in plasma after single dose | | Pre-dose up to 72 hours post-dose |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of subjects with treatment-emergent adverse events (TEAEs) | | From start of study drug administration up to 30 days after last study drug administration |

Thromboembolism

Rivaroxaban, Factor Xa Inhibitors, Antithrombins, Serine Proteinase Inhibitors, Protease Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Anticoagulants

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Treatment A-B<br>Subjects received a single oral dose of 10 mg rivaroxaban tablet in the fasted state on Day 1 (Treatment A) during intervention period 1; and then a single oral dose of 10 mg rivaroxaban oral suspension in the fasted state on Day 1 (Treatment B) during intervention period 2. A wash-out of at least 7 days was maintained between the treatments. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Granules for oral suspension, 10 mg, oral, single dose<br>Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Tablet, 10 mg, oral, single dose<br>| | Experimental: Treatment B-A<br>Subjects received a single oral dose of 10 mg rivaroxaban oral suspension in the fasted state on Day 1 (Treatment B) during intervention period 1; and then a single oral dose of 10 mg rivaroxaban tablet in the fasted state on Day 1 (Treatment A) during intervention period 2. A wash-out of at least 7 days was maintained between the treatments. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Granules for oral suspension, 10 mg, oral, single dose<br>Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Tablet, 10 mg, oral, single dose<br>|

A Trial to Learn How a New Liquid Form of Rivaroxaban Behaves and How Safe it is Compared to the Current Tablet Form of Rivaroxaban in Healthy Male Participants Study Overview ================= Brief Summary ----------------- Researchers were looking for another way to treat people with a blood clot in their veins. Before a treatment can be approved for people to take, researchers do clinical trials to better understand its safety and how it behaves. In this trial, the researchers learned how a new liquid form of rivaroxaban behaved compared to the tablet form in a small number of healthy participants. They also wanted to find out how safe it was. The trial included about 30 white men who were between the ages of 18 and 55. The participants also had a body mass index (BMI) between 18 and 29.9 kilograms per square meter (kg/m^2). BMI is a measurement that uses a person's height and weight to learn how much body fat they have. All the participants in this trial took 10 milliliter of the new form of rivaroxaban (containing 1 milligram [mg] of rivaroxaban per milliliter). Later they also took 10 mg of the current tablet form of rivaroxaban. They took each form 1 time by mouth. This trial was a crossover trial. In a crossover trial, all the participants take all of the treatments, but in a different order. In between the 2 treatments, there was a washout period of at least 7 days. This was done so that the first treatment could leave each participant's body before they took their next treatment. While taking each treatment, the participants stayed at the trial site for 5 days. During this time, they did not eat food for at least 10 hours before and at least 4 hours after taking each treatment. After taking the last treatment, the participants had a final visit about 7 to 14 days later. During the trial, the doctors took blood and urine samples. They also did physical examinations and checked the participants' heart health using an electrocardiogram (ECG). They asked the participants questions about how they were feeling and if they had any medical problems. Official Title ----------------- Single-dose, Open-label, Randomized, 2-way Crossover Bioequivalence Study of 10 mg Granules for Oral Suspension Rivaroxaban Versus 10 mg Tablets Rivaroxaban Under Fasted Condition in Healthy Subjects Conditions ----------------- Thromboembolic Disorders Intervention / Treatment ----------------- * Drug: Rivaroxaban (Xarelto, BAY59-7939) * Drug: Rivaroxaban (Xarelto, BAY59-7939) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: The informed consent had to be signed before any study specific tests or procedures were done Healthy male subjects Age: 18 to 55 years (inclusive) at the screening examination/visit Race: White Body mass index (BMI): above/equal 18 and below/equal 29.9 kg/m^2 Ability to understand and follow instructions Exclusion Criteria: Pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal Known or suspected liver disorders and bile secretion/flow Subjects with thyroid disorders as evidenced by assessment of thyroid stimulating hormone (TSH) levels outside the normal reference range at screening Personal or familial history of genetically muscular diseases Known hypersensitivity to the study drugs (active substances or excipients of the preparations) Known severe allergies e.g. allergies to more than 3 allergens, allergies affecting the lower respiratory tract- allergic asthma, allergies requiring therapy with corticosteroids, urticaria) or significant non-allergic drug reactions Known disorders with increased bleeding risk (e.g., periodontosis, hemorrhoids, acute gastritis, peptic ulcer) Known sensitivity to common causes of bleeding (e.g. nasal) Clinically relevant findings in the electrocardiogram (ECG) such as a second- or third-degree atrioventricular (AV) block, prolongation of the QRS (QRS interval in ECG) complex over 120 msec or of the QTc-interval over 450 msec at the first screening visit Presence or history of arrhythmic disturbances; or known congenital QT (QT interval in ECG) prolongation Systolic blood pressure below 100 or above 140 mmHg Diastolic blood pressure below 50 or above 90 mmHg Heart rate below 50 or above 90 beats/ min Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 55 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Treatment A-B<br>Subjects received a single oral dose of 10 mg rivaroxaban tablet in the fasted state on Day 1 (Treatment A) during intervention period 1; and then a single oral dose of 10 mg rivaroxaban oral suspension in the fasted state on Day 1 (Treatment B) during intervention period 2. A wash-out of at least 7 days was maintained between the treatments. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Granules for oral suspension, 10 mg, oral, single dose<br>Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Tablet, 10 mg, oral, single dose<br>| | Experimental: Treatment B-A<br>Subjects received a single oral dose of 10 mg rivaroxaban oral suspension in the fasted state on Day 1 (Treatment B) during intervention period 1; and then a single oral dose of 10 mg rivaroxaban tablet in the fasted state on Day 1 (Treatment A) during intervention period 2. A wash-out of at least 7 days was maintained between the treatments. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Granules for oral suspension, 10 mg, oral, single dose<br>Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Tablet, 10 mg, oral, single dose<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Area under the concentration versus time curve from zero to infinity (AUC) of rivaroxaban in plasma after single dose | | Pre-dose up to 72 hours post-dose | | AUC from time zero to the last data point greater than (>) lower limit of quantification (LLOQ) (AUC[0-tlast]) of rivaroxaban in plasma after single dose | Area under the concentration versus time curve from zero to infinity (AUC) | Pre-dose up to 72 hours post-dose | | Maximum observed drug concentration (Cmax) of rivaroxaban in plasma after single dose | | Pre-dose up to 72 hours post-dose | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of subjects with treatment-emergent adverse events (TEAEs) | | From start of study drug administration up to 30 days after last study drug administration | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Thromboembolism

NCT05636033

Semantic Networks in Alcohol Use Disorder Patients: Exploratory Study

Alcohol Use Disorder (AUD) is a major public health problem, characterized by a high rate of relapse. Chronic and excessive alcohol consumption notably induces frontal brain alterations and cognitive impairments such as executive dysfunction and an attentional bias for alcohol, participating to the risk of relapse. In effect, AUD patients preferentially process alcohol-related cues, which could reflect a reorganization of the patients' semantic network. The investigators hypothesize that in AUD patients, semantic associations in memory are reorganized with a higher centrality of alcohol-related elements. To the investigators knowledge, no studies have explored semantic associations and/or semantic networks in AUD.~A study, conducted in patients with neurological damage, showed that frontal lesions are associated with excessive strength in semantic associations, and difficulties to generate remote associations. This excessive strength in semantic associations could reduce the ability to inhibit automatisms and to adapt to new context.~Objective: The objective of this study is to explore whether and how AUD patients have a different organization of semantic associations than healthy controls, and whether this reorganization influences the alcohol consumption over the months following the withdrawal. The investigators will also explore how it relates to neuropsychological assessment of flexibility, executive functions, and impulsivity. To these purposes, the investigators will use two original verbal tasks (Free Generation of Associates Task, FGAT and Associative Judgment Task, AJT) assessing word associations and allowing the estimation of semantic networks using graph theory, in combination with neuropsychological testing, in AUD patients and in healthy controls.~Methods: This study will include a group of 30 AUD patients and a group of 30 healthy controls. Both groups will be assessed twice, at baseline (T1; early in abstinence for AUD patients) and after a three-month period (T3). For the two groups, T1 and T3 assessments will include the two semantic association tasks (FGAT and AJT). For AUD patients, assessments will also involve neuropsychological testing of impulsivity, flexibility, and attentional bias. Besides, in AUD patients, data about alcohol consumptions will be collected six weeks (T2) and three months (T3) following the baseline assessment to classify patients as relapsers or abstainers.

Semantic Networks in Alcohol Use Disorder Patients: Exploratory Study

Alcohol Use Disorder

Inclusion Criteria:~For alcohol use disorder patients~Severe alcohol use disorder~French as mother tongue~Right-hander~Patient abstinent from alcohol since 15 to 30 days at the inclusion~Patient free from benzodiazepine since at least 48hours at the inclusion~Patient who gave his informed written consent~Currently in outpatient or inpatient care~For healthy controls~French as mother tongue~Right-hander~Participant who gave his informed written consent~Exclusion Criteria:~For alcohol use disorder patients~Patient under guardianship or under justice safeguard measures~Patient under measure of therapeutic injunction~Pregnancy or breastfeeding declared~Meeting Diagnostic and Statistical Manual 5 (DSM) criteria for substance use disorder other than Tobacco~Meeting DSM-5 criteria for non substance use disorder~Patient presenting severe or progressive disease that interfere with experimental tasks, such as neurological diseases (TBI, epilepsy, stoke) , hepatic diseases, cancer, HIV, Hepatitis C Virus (HCV), and unstable psychiatric comorbidities.~For healthy controls~Participant under guardianship or under justice safeguard measures~Participant under measure of therapeutic injunction~Pregnancy or breastfeeding declared~Meeting DSM-5 criteria for alcohol use disorder~Meeting DSM-5 criteria for substance use disorder other than Tobacco~Meeting DSM-5 criteria for non substance use disorder~Currently under benzodiazepine~Participant presenting severe or progressive disease that interfere with experimental tasks, such as neurological diseases (TBI, epilepsy, stoke) , hepatic diseases, cancer, HIV, HCV, and unstable psychiatric comorbidities.

30 Years

60 Years

All

Accepts Healthy Volunteers

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Description of the semantic associations using FGAT | The Free Generation Associated Tasks will be used in Alcohol use disorder patients and Healthy controls | At baseline (T1) | | Description of the semantic associations using AJT | The Associative Judgment Task will be used in Alcohol use disorder patients and Healthy controls | At baseline (T1) |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Impact of medications on the semantic association performance | | At baseline (T1) | | Impact of age on the semantic association performance | | At baseline (T1) | | Impact of the study level on the semantic association performance | | At baseline (T1) | | Impact of gender on the semantic association performance | | At baseline (T1) | | Impact of the duration of dependence on the semantic association performance | | At baseline (T1) | | Impact of cognitive performance on the semantic association performance | The Go /No Go performance will be collected in Alcohol use disorder patients | At baseline (T1) | | Test of the predictive value of FGAT performance assessed at T1 on alcohol consumption during the six weeks following the Baseline | | Baseline (T1) for FGAT ; T2 (6 weeks after T1) for alcohol consumption | | Test of the predictive value of AJT performance assessed at T1 on alcohol consumption during the six weeks following the Baseline | | Baseline (T1) for AJT ; T2 (6 weeks after T1) for alcohol consumption | | Test of the predictive value of FGAT performance assessed at T1 on alcohol consumption during the three months following the Baseline | | Baseline (T1) for FGAT ; T3 (3 months after T1) for alcohol consumption | | Test of the predictive value of AJT performance assessed at T1 on alcohol consumption during the three months following the Baseline | | Baseline (T1) for AJT ; T3 (3 months after T1) for alcohol consumption | | Evolution of FGAT performance, comparison between alcohol use disorder patients and healthy controls | | T1 (baseline) and T3 (3 months after baseline) | | Evolution of AJT performance, comparison between alcohol use disorder patients and healthy controls | | T1 (baseline) and T3 (3 months after baseline) | | Link between the evolution of FGAT performance and the level of alcohol consumption | The level of alcohol consumption will be assessed using the Timeline Followback method | Baseline (T1) for FGAT and 3 months after baseline (T3) for FGAT and the level of alcohol consumption) | | Link between the evolution of AJT performance and alcohol consumption | The level of alcohol consumption will be assessed using the Timeline Followback method | Baseline (T1) for AJT and 3 months after baseline (T3) for AJT and the level of alcohol consumption) | | Link between the evolution of FGAT performance and the evolution of cognitive performance | The Go /No Go performance will be used in alcohol use disorder patients | Baseline (T1) and 3 months after baseline (T3) | | Link between the evolution of AJT performance and the evolution of cognitive performance | The Go /No Go performance will be used in alcohol use disorder patients | Baseline (T1) and 3 months after baseline (T3) |

alcohol use disorder, semantic association, semantic networks, cognition

Alcoholism, Alcohol Drinking, Drinking Behavior, Alcohol-Related Disorders, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Alcohol use disorder patients<br> | | | Healthy controls<br> | |

Semantic Networks in Alcohol Use Disorder Patients: Exploratory Study Study Overview ================= Brief Summary ----------------- Alcohol Use Disorder (AUD) is a major public health problem, characterized by a high rate of relapse. Chronic and excessive alcohol consumption notably induces frontal brain alterations and cognitive impairments such as executive dysfunction and an attentional bias for alcohol, participating to the risk of relapse. In effect, AUD patients preferentially process alcohol-related cues, which could reflect a reorganization of the patients' semantic network. The investigators hypothesize that in AUD patients, semantic associations in memory are reorganized with a higher centrality of alcohol-related elements. To the investigators knowledge, no studies have explored semantic associations and/or semantic networks in AUD. A study, conducted in patients with neurological damage, showed that frontal lesions are associated with excessive strength in semantic associations, and difficulties to generate remote associations. This excessive strength in semantic associations could reduce the ability to inhibit automatisms and to adapt to new context. Objective: The objective of this study is to explore whether and how AUD patients have a different organization of semantic associations than healthy controls, and whether this reorganization influences the alcohol consumption over the months following the withdrawal. The investigators will also explore how it relates to neuropsychological assessment of flexibility, executive functions, and impulsivity. To these purposes, the investigators will use two original verbal tasks (Free Generation of Associates Task, FGAT and Associative Judgment Task, AJT) assessing word associations and allowing the estimation of semantic networks using graph theory, in combination with neuropsychological testing, in AUD patients and in healthy controls. Methods: This study will include a group of 30 AUD patients and a group of 30 healthy controls. Both groups will be assessed twice, at baseline (T1; early in abstinence for AUD patients) and after a three-month period (T3). For the two groups, T1 and T3 assessments will include the two semantic association tasks (FGAT and AJT). For AUD patients, assessments will also involve neuropsychological testing of impulsivity, flexibility, and attentional bias. Besides, in AUD patients, data about alcohol consumptions will be collected six weeks (T2) and three months (T3) following the baseline assessment to classify patients as relapsers or abstainers. Official Title ----------------- Semantic Networks in Alcohol Use Disorder Patients: Exploratory Study Conditions ----------------- Alcohol Use Disorder Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: For alcohol use disorder patients Severe alcohol use disorder French as mother tongue Right-hander Patient abstinent from alcohol since 15 to 30 days at the inclusion Patient free from benzodiazepine since at least 48hours at the inclusion Patient who gave his informed written consent Currently in outpatient or inpatient care For healthy controls French as mother tongue Right-hander Participant who gave his informed written consent Exclusion Criteria: For alcohol use disorder patients Patient under guardianship or under justice safeguard measures Patient under measure of therapeutic injunction Pregnancy or breastfeeding declared Meeting Diagnostic and Statistical Manual 5 (DSM) criteria for substance use disorder other than Tobacco Meeting DSM-5 criteria for non substance use disorder Patient presenting severe or progressive disease that interfere with experimental tasks, such as neurological diseases (TBI, epilepsy, stoke) , hepatic diseases, cancer, HIV, Hepatitis C Virus (HCV), and unstable psychiatric comorbidities. For healthy controls Participant under guardianship or under justice safeguard measures Participant under measure of therapeutic injunction Pregnancy or breastfeeding declared Meeting DSM-5 criteria for alcohol use disorder Meeting DSM-5 criteria for substance use disorder other than Tobacco Meeting DSM-5 criteria for non substance use disorder Currently under benzodiazepine Participant presenting severe or progressive disease that interfere with experimental tasks, such as neurological diseases (TBI, epilepsy, stoke) , hepatic diseases, cancer, HIV, HCV, and unstable psychiatric comorbidities. Ages Eligible for Study ----------------- Minimum Age: 30 Years Maximum Age: 60 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Alcohol use disorder patients<br> | | | Healthy controls<br> | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Description of the semantic associations using FGAT | The Free Generation Associated Tasks will be used in Alcohol use disorder patients and Healthy controls | At baseline (T1) | | Description of the semantic associations using AJT | The Associative Judgment Task will be used in Alcohol use disorder patients and Healthy controls | At baseline (T1) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Impact of medications on the semantic association performance | | At baseline (T1) | | Impact of age on the semantic association performance | | At baseline (T1) | | Impact of the study level on the semantic association performance | | At baseline (T1) | | Impact of gender on the semantic association performance | | At baseline (T1) | | Impact of the duration of dependence on the semantic association performance | | At baseline (T1) | | Impact of cognitive performance on the semantic association performance | The Go /No Go performance will be collected in Alcohol use disorder patients | At baseline (T1) | | Test of the predictive value of FGAT performance assessed at T1 on alcohol consumption during the six weeks following the Baseline | | Baseline (T1) for FGAT ; T2 (6 weeks after T1) for alcohol consumption | | Test of the predictive value of AJT performance assessed at T1 on alcohol consumption during the six weeks following the Baseline | | Baseline (T1) for AJT ; T2 (6 weeks after T1) for alcohol consumption | | Test of the predictive value of FGAT performance assessed at T1 on alcohol consumption during the three months following the Baseline | | Baseline (T1) for FGAT ; T3 (3 months after T1) for alcohol consumption | | Test of the predictive value of AJT performance assessed at T1 on alcohol consumption during the three months following the Baseline | | Baseline (T1) for AJT ; T3 (3 months after T1) for alcohol consumption | | Evolution of FGAT performance, comparison between alcohol use disorder patients and healthy controls | | T1 (baseline) and T3 (3 months after baseline) | | Evolution of AJT performance, comparison between alcohol use disorder patients and healthy controls | | T1 (baseline) and T3 (3 months after baseline) | | Link between the evolution of FGAT performance and the level of alcohol consumption | The level of alcohol consumption will be assessed using the Timeline Followback method | Baseline (T1) for FGAT and 3 months after baseline (T3) for FGAT and the level of alcohol consumption) | | Link between the evolution of AJT performance and alcohol consumption | The level of alcohol consumption will be assessed using the Timeline Followback method | Baseline (T1) for AJT and 3 months after baseline (T3) for AJT and the level of alcohol consumption) | | Link between the evolution of FGAT performance and the evolution of cognitive performance | The Go /No Go performance will be used in alcohol use disorder patients | Baseline (T1) and 3 months after baseline (T3) | | Link between the evolution of AJT performance and the evolution of cognitive performance | The Go /No Go performance will be used in alcohol use disorder patients | Baseline (T1) and 3 months after baseline (T3) | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- alcohol use disorder, semantic association, semantic networks, cognition

NCT03458390

Use of a Colon Irrigation Device as a Preparation for a Colon Visualization Procedure

A prospective, single center, study to evaluate the effectiveness of the HyGIeaCare Prep when used in combination with the PillCam COLON; the hypothesis is that the HyGIeaCare Prep will be easier for the patients to tolerate, and the results will be as good as the existing oral preparation.

Patients who agree to participate in the study will have their HyGIeaCare procedure and then will present to the PillCam COLON room, in the same suite for the PillCam COLON procedure.~The commercial preparations for the PillCam COLON procedure will be the same, except the HyGIeaCare procedure will replace the split polyethylene glycol-electrolyte solution preparation.~2-days prior:~Normal diet~10 glasses of liquid~1-day prior:~Clear liquid diet all day~Dulcolax 2 tabs at 2pm and 2 tabs at 8pm~Nothing by mouth after midnight~Day of Procedure:~6am- Dulcolax 2 tabs~8am- HyGIeaCare Procedure~9am- ingest PillCam Colon~10am- ingest Reglan~At small bowel detection, drink 10oz SUPREP and 32oz water~3hrs later- drink 10oz SUPREP and 32oz water~2hrs later- insert suppository~2hrs later- light meal

Colon Irrigation Using HyGIeaCare as Prep for PillCam COLON Procedure

Screening Colonoscopy

* Device: HyGIeaCare colon irrigation

Inclusion Criteria:~Patient referred for the PillCam COLON procedure~Exclusion Criteria:~-~HyGIeaCare:~Patient has any condition that, in the opinion of the investigator, may adversely affect the compliance or safety of the patient or would limit the patient's ability to complete the study~Patient is treated long-term with narcotics.~Patient does not have any of the contraindications listed below:~Cardiac: Congestive heart failure (NYHA class III or IV or Ejection Fraction <50%)~GastrointestinaI: Intestinal perforation, carcinoma of the rectum, Fissures or fistula, Severe hemorrhoids, Abdominal hernia, recent colon or rectal surgery, abdominal surgery~Genitourinary: Renal insufficiency (CC < 60 ml/min/173m2), cirrhosis with ascites~Abdominal surgery within the last 6 months~Pregnancy~PillCam COLON:~Subject has dysphagia or any swallowing disorder~Subject has congestive heart failure~Subject has Diabetes type I.~Subject has had prior abdominal surgery other than uncomplicated procedures that would be unlikely to lead to bowel obstruction based on the clinical judgment of the investigator~Subject has a cardiac pacemaker or other implanted electro medical device.~Subject has any allergy or other known contraindication to the medications used in the study~Subject is expected to undergo MRI examination within 7 days after ingestion of the capsule.~Subject with any condition believed to have an increased risk for capsule retention such as Crohn's disease, intestinal tumors, radiation enteritis, and incomplete colonoscopies due to obstructions or NSAID enteropathy.~Subject with gastrointestinal motility disorders~Subject has known delayed gastric emptying~Subject has any condition, which precludes compliance with study and/or device instructions.~Women who are either pregnant or nursing at the time of screening, or are of child-bearing potential and do not practice medically acceptable methods of contraception.~Subject suffers from life threatening conditions~Subject currently participating in another clinical study

18 Years

80 Years

All

Accepts Healthy Volunteers

Primary Purpose: Device Feasibility Intervention Model: Single Group Assignment Interventional Model Description: HyGIeaCare colon irrigation procedure and PillCam COLON procedure Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Effectiveness of colon irrigation | Effectiveness of the HyGIeaCare Prep will be measured using a 5-point scale to evaluate the visual quality of bowel cleanliness identified in the PillCam Colon video (Excellent, Good, Fair, Adequate, Poor). | Immediately after colon irrigation, PillCam COLON will be administered. A video will be taken of the procedure which will be used to measure the effectiveness of the colon irrigation. |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Evaluation of adverse events | The CTCAE tool will be used to evaluate outcomes | To be evaluated the day of the procedure | | Evaluation of patient satisfaction | A standardized questionnaire will be used to measure outcomes | To be evaluated on the day of the procedure |

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: HyGIeaCare and PillCam COLON<br>Patient will receive the HyGIeaCare colon irrigation prior to their PillCam COLON procedure | Device: HyGIeaCare colon irrigation<br>* PillCam COLON for visualization of bowel lining<br>* Other names: PillCam COLON;|

Use of a Colon Irrigation Device as a Preparation for a Colon Visualization Procedure Study Overview ================= Brief Summary ----------------- A prospective, single center, study to evaluate the effectiveness of the HyGIeaCare Prep when used in combination with the PillCam COLON; the hypothesis is that the HyGIeaCare Prep will be easier for the patients to tolerate, and the results will be as good as the existing oral preparation. Detailed Description ----------------- Patients who agree to participate in the study will have their HyGIeaCare procedure and then will present to the PillCam COLON room, in the same suite for the PillCam COLON procedure. The commercial preparations for the PillCam COLON procedure will be the same, except the HyGIeaCare procedure will replace the split polyethylene glycol-electrolyte solution preparation. 2-days prior: Normal diet 10 glasses of liquid 1-day prior: Clear liquid diet all day Dulcolax 2 tabs at 2pm and 2 tabs at 8pm Nothing by mouth after midnight Day of Procedure: 6am- Dulcolax 2 tabs 8am- HyGIeaCare Procedure 9am- ingest PillCam Colon 10am- ingest Reglan At small bowel detection, drink 10oz SUPREP and 32oz water 3hrs later- drink 10oz SUPREP and 32oz water 2hrs later- insert suppository 2hrs later- light meal Official Title ----------------- Colon Irrigation Using HyGIeaCare as Prep for PillCam COLON Procedure Conditions ----------------- Screening Colonoscopy Intervention / Treatment ----------------- * Device: HyGIeaCare colon irrigation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patient referred for the PillCam COLON procedure Exclusion Criteria: - HyGIeaCare: Patient has any condition that, in the opinion of the investigator, may adversely affect the compliance or safety of the patient or would limit the patient's ability to complete the study Patient is treated long-term with narcotics. Patient does not have any of the contraindications listed below: Cardiac: Congestive heart failure (NYHA class III or IV or Ejection Fraction <50%) GastrointestinaI: Intestinal perforation, carcinoma of the rectum, Fissures or fistula, Severe hemorrhoids, Abdominal hernia, recent colon or rectal surgery, abdominal surgery Genitourinary: Renal insufficiency (CC < 60 ml/min/173m2), cirrhosis with ascites Abdominal surgery within the last 6 months Pregnancy PillCam COLON: Subject has dysphagia or any swallowing disorder Subject has congestive heart failure Subject has Diabetes type I. Subject has had prior abdominal surgery other than uncomplicated procedures that would be unlikely to lead to bowel obstruction based on the clinical judgment of the investigator Subject has a cardiac pacemaker or other implanted electro medical device. Subject has any allergy or other known contraindication to the medications used in the study Subject is expected to undergo MRI examination within 7 days after ingestion of the capsule. Subject with any condition believed to have an increased risk for capsule retention such as Crohn's disease, intestinal tumors, radiation enteritis, and incomplete colonoscopies due to obstructions or NSAID enteropathy. Subject with gastrointestinal motility disorders Subject has known delayed gastric emptying Subject has any condition, which precludes compliance with study and/or device instructions. Women who are either pregnant or nursing at the time of screening, or are of child-bearing potential and do not practice medically acceptable methods of contraception. Subject suffers from life threatening conditions Subject currently participating in another clinical study Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Device Feasibility Intervention Model: Single Group Assignment Interventional Model Description: HyGIeaCare colon irrigation procedure and PillCam COLON procedure Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: HyGIeaCare and PillCam COLON<br>Patient will receive the HyGIeaCare colon irrigation prior to their PillCam COLON procedure | Device: HyGIeaCare colon irrigation<br>* PillCam COLON for visualization of bowel lining<br>* Other names: PillCam COLON;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Effectiveness of colon irrigation | Effectiveness of the HyGIeaCare Prep will be measured using a 5-point scale to evaluate the visual quality of bowel cleanliness identified in the PillCam Colon video (Excellent, Good, Fair, Adequate, Poor). | Immediately after colon irrigation, PillCam COLON will be administered. A video will be taken of the procedure which will be used to measure the effectiveness of the colon irrigation. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Evaluation of adverse events | The CTCAE tool will be used to evaluate outcomes | To be evaluated the day of the procedure | | Evaluation of patient satisfaction | A standardized questionnaire will be used to measure outcomes | To be evaluated on the day of the procedure |

NCT04563884

Validity of the French Version of Deafness Questionnaires for Children and Adolescents

The care of deafness in children is difficult and the relevance of interventions is difficult to evaluate based on audiometric measurements alone.~Generic pediatric quality of life tools have been validated and used, among other things, to assess the quality of life of children with deafness. However, these non-specific tools do not make it possible to precisely target which factors and interventions are the most important for the quality of life in this population.~Achieving a score to monitor the quality of life objectively over time is fundamental to verify the effectiveness of interventions, and assess the impact on the child. There is currently no validated test in French for any of these uses and populations.~The objective of the study is to adapt the questionnaires PEACH, SSQ child (SSQ-C) and SSQ parents (SSQ-P) to the French child, and statistically measure their internal and external validity by comparing them to a control group.~The validation of these three tests (PEACH, SSQ-P, SSQ-C) would make it possible to assess the hearing performance and quality of life of almost the entire pediatric population, for use in both clinical and academic practice.

Neonatal sensorineural hearing loss is a frequent pathology, affecting around 800 newborns per year in France, or an incidence of 0.8 to 1.3 per 1000 births, comparable to other industrialized countries. It can affect the development of speech and language and lead to impaired quality of life.~Studies have shown that children with hearing loss score lower on general quality-of-life measurement tools, compared to their normal-hearing peers. A poorer quality of life in patients with sensorineural hearing loss may also reflect physical, academic, social or emotional difficulties. They are also exposed to an increased risk of poor development of language and social skills, as well as an increased risk of developing psychiatric pathologies.~The care of deafness in children is difficult and the relevance of interventions is difficult to evaluate based on audiometric measurements alone.~Generic pediatric quality of life tools have been validated and used, among other things, to assess the quality of life of children with deafness. However, these non-specific tools do not make it possible to precisely target which factors and interventions are the most important for the quality of life in this population.~Achieving a score to monitor the quality of life objectively over time is fundamental to verify the effectiveness of interventions, and assess the impact on the child. There is currently no validated test in French for any of these uses and populations.~The Parents' Evaluation of Aural/Oral Performance of Children (PEACH) is a hetero-evaluation score used to study the quality of a child's communication from an early age (from 4 months in some studies) and up to 13 years. This tool is specifically designed for children with hearing aids or a cochlear implant. It has been translated into Swedish and Spanish and used in numerous international publications.~The Speech, Spatial and Qualities of Hearing Scale (SSQ) is an adult self-assessment score assessing, in three categories, the performance of speech comprehension, spatial hearing and hearing quality. It is widely used internationally in its adult version.~This adult score has been adapted and used for the pediatric population in a hetero-evaluation score by parents (SSQ-P) from 5 years old, and a simplified score (SSQ-C) usable by children> 11 years.~In addition, the authors of the adult SSQ also prepared and validated a Handicap questionnaire to target the impact of hearing loss on quality of life, and integrated into the SSQ self-assessment.~The objective of the study is to adapt the questionnaires PEACH, SSQ child (SSQ-C) and SSQ parents (SSQ-P) to the French child, and statistically measure their internal and external validity by comparing them to a control group.~The validation of these three tests (PEACH, SSQ-P, SSQ-C) would make it possible to assess the hearing performance and quality of life of almost the entire pediatric population, for use in both clinical and academic practice.

Validity of the French Version of Deafness Questionnaires for Children and Adolescents

Deafness

* Other: Questionnaires

Inclusion Criteria:~Minors aged 12 months to 17 years (inclusive)~Patients followed in consultation at Necker Hospital in the Pediatric ENT department~holders of parental authority not opposed to participation in the study~Patients :~Patients with deafness with mean tonal thresholds of at least 30dB, uni- or bilateral~Perceptual or transmission deafness or mixed~Controls:~Patients not presenting a hearing disorder at the time of inclusion or in his or her history~Examination of the normal eardrums~No history of ear surgery~Exclusion Criteria:~Psychomotor retardation~Abnormal neurological examination~Mother tongue of the child and parents other than French

12 Months

17 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Paired student t-test | Reproducibility of the questionnaire completed by a subject at 15 days apart | 1 year | | Cronbach alpha test | Internal consistency | 1 year | | Item-total Pearson correlation | Measure of reliability | 1 year | | Principal components analysis | Measure of efficiency | 1 year | | Receiver Operating Characteristic (ROC) curve | Limit value of normality | 1 year |

Deafness, Children, SSQ questionnaire, PEACH questionnaire

Deafness, Hearing Loss, Hearing Disorders, Ear Diseases, Otorhinolaryngologic Diseases, Sensation Disorders, Neurologic Manifestations, Nervous System Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Patients with deafness<br>Patients aged 12 months to 17 years with deafness | Other: Questionnaires<br>* Children 12 months to 5 years old will receive PEACH alone, children 5 years old to 11 years old will receive PEACH and SSQ-P, and children and adolescents over 11 years old will receive SSQ-P and SSQ-C (even between 11 and 13 years old, the PEACH also).~Questionnaires will be completed twice, 15 days apart.<br>* Other names: The Parents' Evaluation of Aural/Oral Performance of Children (PEACH). The Speech, Spatial and Qualities of Hearing Scale (SSQ);| | Controls<br>Normal-hearing patients aged 12 months to 17 years | Other: Questionnaires<br>* Children 12 months to 5 years old will receive PEACH alone, children 5 years old to 11 years old will receive PEACH and SSQ-P, and children and adolescents over 11 years old will receive SSQ-P and SSQ-C (even between 11 and 13 years old, the PEACH also).~Questionnaires will be completed twice, 15 days apart.<br>* Other names: The Parents' Evaluation of Aural/Oral Performance of Children (PEACH). The Speech, Spatial and Qualities of Hearing Scale (SSQ);|

Validity of the French Version of Deafness Questionnaires for Children and Adolescents Study Overview ================= Brief Summary ----------------- The care of deafness in children is difficult and the relevance of interventions is difficult to evaluate based on audiometric measurements alone. Generic pediatric quality of life tools have been validated and used, among other things, to assess the quality of life of children with deafness. However, these non-specific tools do not make it possible to precisely target which factors and interventions are the most important for the quality of life in this population. Achieving a score to monitor the quality of life objectively over time is fundamental to verify the effectiveness of interventions, and assess the impact on the child. There is currently no validated test in French for any of these uses and populations. The objective of the study is to adapt the questionnaires PEACH, SSQ child (SSQ-C) and SSQ parents (SSQ-P) to the French child, and statistically measure their internal and external validity by comparing them to a control group. The validation of these three tests (PEACH, SSQ-P, SSQ-C) would make it possible to assess the hearing performance and quality of life of almost the entire pediatric population, for use in both clinical and academic practice. Detailed Description ----------------- Neonatal sensorineural hearing loss is a frequent pathology, affecting around 800 newborns per year in France, or an incidence of 0.8 to 1.3 per 1000 births, comparable to other industrialized countries. It can affect the development of speech and language and lead to impaired quality of life. Studies have shown that children with hearing loss score lower on general quality-of-life measurement tools, compared to their normal-hearing peers. A poorer quality of life in patients with sensorineural hearing loss may also reflect physical, academic, social or emotional difficulties. They are also exposed to an increased risk of poor development of language and social skills, as well as an increased risk of developing psychiatric pathologies. The care of deafness in children is difficult and the relevance of interventions is difficult to evaluate based on audiometric measurements alone. Generic pediatric quality of life tools have been validated and used, among other things, to assess the quality of life of children with deafness. However, these non-specific tools do not make it possible to precisely target which factors and interventions are the most important for the quality of life in this population. Achieving a score to monitor the quality of life objectively over time is fundamental to verify the effectiveness of interventions, and assess the impact on the child. There is currently no validated test in French for any of these uses and populations. The Parents' Evaluation of Aural/Oral Performance of Children (PEACH) is a hetero-evaluation score used to study the quality of a child's communication from an early age (from 4 months in some studies) and up to 13 years. This tool is specifically designed for children with hearing aids or a cochlear implant. It has been translated into Swedish and Spanish and used in numerous international publications. The Speech, Spatial and Qualities of Hearing Scale (SSQ) is an adult self-assessment score assessing, in three categories, the performance of speech comprehension, spatial hearing and hearing quality. It is widely used internationally in its adult version. This adult score has been adapted and used for the pediatric population in a hetero-evaluation score by parents (SSQ-P) from 5 years old, and a simplified score (SSQ-C) usable by children> 11 years. In addition, the authors of the adult SSQ also prepared and validated a Handicap questionnaire to target the impact of hearing loss on quality of life, and integrated into the SSQ self-assessment. The objective of the study is to adapt the questionnaires PEACH, SSQ child (SSQ-C) and SSQ parents (SSQ-P) to the French child, and statistically measure their internal and external validity by comparing them to a control group. The validation of these three tests (PEACH, SSQ-P, SSQ-C) would make it possible to assess the hearing performance and quality of life of almost the entire pediatric population, for use in both clinical and academic practice. Official Title ----------------- Validity of the French Version of Deafness Questionnaires for Children and Adolescents Conditions ----------------- Deafness Intervention / Treatment ----------------- * Other: Questionnaires Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Minors aged 12 months to 17 years (inclusive) Patients followed in consultation at Necker Hospital in the Pediatric ENT department holders of parental authority not opposed to participation in the study Patients : Patients with deafness with mean tonal thresholds of at least 30dB, uni- or bilateral Perceptual or transmission deafness or mixed Controls: Patients not presenting a hearing disorder at the time of inclusion or in his or her history Examination of the normal eardrums No history of ear surgery Exclusion Criteria: Psychomotor retardation Abnormal neurological examination Mother tongue of the child and parents other than French Ages Eligible for Study ----------------- Minimum Age: 12 Months Maximum Age: 17 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Patients with deafness<br>Patients aged 12 months to 17 years with deafness | Other: Questionnaires<br>* Children 12 months to 5 years old will receive PEACH alone, children 5 years old to 11 years old will receive PEACH and SSQ-P, and children and adolescents over 11 years old will receive SSQ-P and SSQ-C (even between 11 and 13 years old, the PEACH also). Questionnaires will be completed twice, 15 days apart.<br>* Other names: The Parents' Evaluation of Aural/Oral Performance of Children (PEACH). The Speech, Spatial and Qualities of Hearing Scale (SSQ);| | Controls<br>Normal-hearing patients aged 12 months to 17 years | Other: Questionnaires<br>* Children 12 months to 5 years old will receive PEACH alone, children 5 years old to 11 years old will receive PEACH and SSQ-P, and children and adolescents over 11 years old will receive SSQ-P and SSQ-C (even between 11 and 13 years old, the PEACH also). Questionnaires will be completed twice, 15 days apart.<br>* Other names: The Parents' Evaluation of Aural/Oral Performance of Children (PEACH). The Speech, Spatial and Qualities of Hearing Scale (SSQ);| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Paired student t-test | Reproducibility of the questionnaire completed by a subject at 15 days apart | 1 year | | Cronbach alpha test | Internal consistency | 1 year | | Item-total Pearson correlation | Measure of reliability | 1 year | | Principal components analysis | Measure of efficiency | 1 year | | Receiver Operating Characteristic (ROC) curve | Limit value of normality | 1 year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Deafness, Children, SSQ questionnaire, PEACH questionnaire

NCT00003580

Amifostine to Treat Side Effects of Treatment in Patients Receiving Radiation Therapy and Cisplatin for Advanced Head and Neck Cancer

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Drugs such as amifostine may protect normal cells from the side effects of chemotherapy and radiation therapy.~PURPOSE: Phase II trial to study the effectiveness of amifostine in treating side effects of treatment in patients receiving radiation therapy and cisplatin for advanced head and neck cancer.

OBJECTIVES: I. Determine the efficacy of amifostine in alleviating treatment related mucositis associated with targeted supradose cisplatin and concurrent radiotherapy (RADPLAT protocol) in patients with stage III or IV squamous cell carcinoma of the head and neck. II. Determine the efficacy of amifostine in alleviating other treatment related morbidities associated with this protocol in these patients.~OUTLINE: This is an open label, multicenter study of amifostine. Patients receive external beam radiotherapy 5 days a week for approximately 6.5-7.5 weeks. Concurrent with radiotherapy, patients receive amifostine IV over 10 minutes, 30 minutes prior to cisplatin, then cisplatin intra-arterially over 3-5 minutes. Chemotherapy and amifostine course is repeated every week for 4 weeks. Patients are followed at 1 month.~PROJECTED ACCRUAL: Approximately 30 patients will be accrued into this study over 12-18 months.

Phase II Study - Efficacy of Amifostine in Alleviating Toxicity Associated With Targeted Supradose Cisplatin and Concomitant Radiation Therapy (RADPLAT) in Head and Neck Cancer

Drug/Agent Toxicity by Tissue/Organ, Head and Neck Cancer, Oral Complications, Radiation Toxicity

* Drug: amifostine trihydrate * Drug: cisplatin * Radiation: radiation therapy

DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the oral cavity, nasopharynx, oropharynx, hypopharynx, or larynx Previously untreated Stage III or IV No distant metastatic disease~PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: SGOT and SGPT no greater than 2.5 times upper limit of normal Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance greater than 61 mL/min Other: No history of any underlying medical or psychiatric illness Not pregnant or nursing Effective contraception required of all fertile patients~PRIOR CONCURRENT THERAPY: No prior therapy for head and neck cancer Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: At least 24 hours since prior antihypertensive medication

18 Years

All

No

Primary Purpose: Supportive Care

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- |

radiation toxicity, oral complications, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, drug/agent toxicity by tissue/organ

Amifostine, Radiation-Protective Agents, Protective Agents, Physiological Effects of Drugs

| Intervention/Treatment | | --- | |Drug: amifostine trihydrate|nan| |Drug: cisplatin|nan| |Radiation: radiation therapy|nan|

Amifostine to Treat Side Effects of Treatment in Patients Receiving Radiation Therapy and Cisplatin for Advanced Head and Neck Cancer Study Overview ================= Brief Summary ----------------- RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Drugs such as amifostine may protect normal cells from the side effects of chemotherapy and radiation therapy. PURPOSE: Phase II trial to study the effectiveness of amifostine in treating side effects of treatment in patients receiving radiation therapy and cisplatin for advanced head and neck cancer. Detailed Description ----------------- OBJECTIVES: I. Determine the efficacy of amifostine in alleviating treatment related mucositis associated with targeted supradose cisplatin and concurrent radiotherapy (RADPLAT protocol) in patients with stage III or IV squamous cell carcinoma of the head and neck. II. Determine the efficacy of amifostine in alleviating other treatment related morbidities associated with this protocol in these patients. OUTLINE: This is an open label, multicenter study of amifostine. Patients receive external beam radiotherapy 5 days a week for approximately 6.5-7.5 weeks. Concurrent with radiotherapy, patients receive amifostine IV over 10 minutes, 30 minutes prior to cisplatin, then cisplatin intra-arterially over 3-5 minutes. Chemotherapy and amifostine course is repeated every week for 4 weeks. Patients are followed at 1 month. PROJECTED ACCRUAL: Approximately 30 patients will be accrued into this study over 12-18 months. Official Title ----------------- Phase II Study - Efficacy of Amifostine in Alleviating Toxicity Associated With Targeted Supradose Cisplatin and Concomitant Radiation Therapy (RADPLAT) in Head and Neck Cancer Conditions ----------------- Drug/Agent Toxicity by Tissue/Organ, Head and Neck Cancer, Oral Complications, Radiation Toxicity Intervention / Treatment ----------------- * Drug: amifostine trihydrate * Drug: cisplatin * Radiation: radiation therapy Participation Criteria ================= Eligibility Criteria ----------------- DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the oral cavity, nasopharynx, oropharynx, hypopharynx, or larynx Previously untreated Stage III or IV No distant metastatic disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: SGOT and SGPT no greater than 2.5 times upper limit of normal Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance greater than 61 mL/min Other: No history of any underlying medical or psychiatric illness Not pregnant or nursing Effective contraception required of all fertile patients PRIOR CONCURRENT THERAPY: No prior therapy for head and neck cancer Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: At least 24 hours since prior antihypertensive medication Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Arms and Interventions | Intervention/Treatment | | --- | |Drug: amifostine trihydrate|nan| |Drug: cisplatin|nan| |Radiation: radiation therapy|nan| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- radiation toxicity, oral complications, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, drug/agent toxicity by tissue/organ

NCT05074797

Epidemology of Acute Kidney Injury in Diabetic Patients Infected With covid_19 In Assiut University Hospital

The novel coronavirus SARS-CoV-2 was identified as the causative agent for a series of atypical respiratory diseases in Wuhan, China in December of 2019(.1) The disease termed COVID-19, was officially declared a pandemic by the World Health Organization on March 11, 2020. SARS-CoV-2 contains a single-stranded, positive-sense RNA genome surrounded by an extracellular membrane containing a series of spike glycoproteins resembling a crown.COVID-19 infection results in diverse symptoms and morbidity depending on individual genetics, ethnicity, age, and geographic location. In severe cases, COVID-19 pathophysiology includes destruction of lung epithelial cells, thrombosis, hypercoagulation, and vascular leak leading to sepsis.(2) COVID-19 risk factors include cardiovascular disease, hypertension, and diabetes.(2)

Notably, in several studies, diabetes is one of the most reported comorbidities with poor prognosis in patients with severe COVID-19 due to Compromised innate immunity, pro-inflammatory cytokine reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists. (3) On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus by direct β-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir).(4) Nearly half of critically ill patients would develop AKI at some point during their ICU admission.(5) Acute kidney injury (AKI) has been reported to be the second observed complication in deceased patients after ARDS.it is reported that patients who died with covid19 had different degrees of AKI .The pathogenesis of kidney injury in patients infected with covid19 is multifactorial: (1) prerenal azotemia, ATN can occur owing to many contributing factors including volume depletion, cytokine storm, hypoxia, shock, or rhabdomyolysis (2) proximal tubular injury, (3) glomerulopathy, (4) thrombotic microangiopathy, and (5)complications from the treatment of COVID_19. (6)

Epidemology of Acute Kidney Injury in Diabetic Patients Infected With covid_19 In Assiut University Hospital

Acute Kidney Injury Due to covid_19

* Diagnostic Test: laboratory

Inclusion Criteria:~patients admitted because of COVID-19 infetion.~Exclusion Criteria:~Patients with ESRD on regular dialysis ,Patients with stage 4 or 5 non-dialysis if the condition proven to be progression of the already known diagnosis.

All

Accepts Healthy Volunteers

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | percentage of AKI in covid_19 in diabetic pt | diabetic pt with AKI due to infection with covid _19 | 6 months |

Acute Kidney Injury, Wounds and Injuries, Renal Insufficiency, Kidney Diseases, Urologic Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | covid not diabetic with AKI<br>AKI in pt with covid_19 not diabetic | Diagnostic Test: laboratory<br>* laboratory data<br>| | AKI in covid_19 in diabetic<br>AKI in covid_19 in diabetic pt | Diagnostic Test: laboratory<br>* laboratory data<br>| | covid_19 in diabetic<br>covid_19 in diabetic without AKI | Diagnostic Test: laboratory<br>* laboratory data<br>|

Epidemology of Acute Kidney Injury in Diabetic Patients Infected With covid_19 In Assiut University Hospital Study Overview ================= Brief Summary ----------------- The novel coronavirus SARS-CoV-2 was identified as the causative agent for a series of atypical respiratory diseases in Wuhan, China in December of 2019(.1) The disease termed COVID-19, was officially declared a pandemic by the World Health Organization on March 11, 2020. SARS-CoV-2 contains a single-stranded, positive-sense RNA genome surrounded by an extracellular membrane containing a series of spike glycoproteins resembling a crown.COVID-19 infection results in diverse symptoms and morbidity depending on individual genetics, ethnicity, age, and geographic location. In severe cases, COVID-19 pathophysiology includes destruction of lung epithelial cells, thrombosis, hypercoagulation, and vascular leak leading to sepsis.(2) COVID-19 risk factors include cardiovascular disease, hypertension, and diabetes.(2) Detailed Description ----------------- Notably, in several studies, diabetes is one of the most reported comorbidities with poor prognosis in patients with severe COVID-19 due to Compromised innate immunity, pro-inflammatory cytokine reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists. (3) On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus by direct β-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir).(4) Nearly half of critically ill patients would develop AKI at some point during their ICU admission.(5) Acute kidney injury (AKI) has been reported to be the second observed complication in deceased patients after ARDS.it is reported that patients who died with covid19 had different degrees of AKI .The pathogenesis of kidney injury in patients infected with covid19 is multifactorial: (1) prerenal azotemia, ATN can occur owing to many contributing factors including volume depletion, cytokine storm, hypoxia, shock, or rhabdomyolysis (2) proximal tubular injury, (3) glomerulopathy, (4) thrombotic microangiopathy, and (5)complications from the treatment of COVID_19. (6) Official Title ----------------- Epidemology of Acute Kidney Injury in Diabetic Patients Infected With covid_19 In Assiut University Hospital Conditions ----------------- Acute Kidney Injury Due to covid_19 Intervention / Treatment ----------------- * Diagnostic Test: laboratory Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: patients admitted because of COVID-19 infetion. Exclusion Criteria: Patients with ESRD on regular dialysis ,Patients with stage 4 or 5 non-dialysis if the condition proven to be progression of the already known diagnosis. Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | covid not diabetic with AKI<br>AKI in pt with covid_19 not diabetic | Diagnostic Test: laboratory<br>* laboratory data<br>| | AKI in covid_19 in diabetic<br>AKI in covid_19 in diabetic pt | Diagnostic Test: laboratory<br>* laboratory data<br>| | covid_19 in diabetic<br>covid_19 in diabetic without AKI | Diagnostic Test: laboratory<br>* laboratory data<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | percentage of AKI in covid_19 in diabetic pt | diabetic pt with AKI due to infection with covid _19 | 6 months |

NCT01963052

ASG-15ME is a Study of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

The objectives of this study are to assess the safety, pharmacokinetics, immunogenicity and anti-tumor activity of AGS15E in subjects with metastatic urothelial cancer who failed at least one prior chemotherapy regimen for metastatic disease.

All subjects will receive a single intravenous infusion of AGS15E once weekly for 3 weeks of every 4 weeks. A cycle is 4 weeks. Subjects will continue treatment until disease progression, intolerability of AGS15E, investigator decision, or consent withdrawal.~In subjects who discontinue therapy without documented disease progression and who still consent to study procedures, every effort should be made to continue monitoring their disease status by radiographic imaging until progression is documented, or new anticancer therapy, or death. All subjects will continue to be followed for survival until withdrawal of consent or study closure.~If assessed as complete response (CR) or partial response (PR) per local review a confirmatory scan will be performed no less than 4 weeks from previous scan and preferably at week 5. Tumor imaging should also be performed whenever disease progression is suspected.~Images will be sent to a central third party imaging vendor for an independent assessment per RECIST version 1.1. Although the imaging studies will be reviewed by a central third party imaging vendor in a retrospective fashion, all clinical decisions will be based on the interpretation of the investigator at the site treating the subject.~Post-Treatment Follow-up Progression Free Survival:~Subjects who discontinued study treatment for reasons other than radiographic disease progression will continue for a maximum of up to 12 months following the last dose of study drug until radiologically confirmed progression, initiation of a new anticancer therapy, death, loss to follow-up or withdraw consent for further follow-up, whichever of these events occurs first. The purpose of the post-treatment follow-up is to ascertain the duration of progression-free survival for all subjects enrolled in the study.

A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

Metastatic Urothelial Cancer

* Drug: AGS15E

Inclusion Criteria:~Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.~Part A: Subject must have failed at least one prior chemotherapy regimen for metastatic disease and/or is unfit for cisplatin-based chemotherapy.~Part B: Subject must not have received any prior lines of chemotherapy in the metastatic setting (prior treatment with immunotherapy is allowed).~Part C (CPI-Treated Expansion): Subject must have received prior treatment with a CPI in the metastatic setting~Subjects must have measureable disease according to RECIST (version 1.1).~Part A and C: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1~Part B: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2~Life expectancy of ≥ 3 months~Adequate hematologic function~Parts A and C: Renal function, as follows: serum creatinine ≤ 2.0 mg/dL, or measured 24 hour creatinine clearance of ≥ 45 mL/min~Part B: Renal function, as follows: creatinine clearance estimate ≥ 15 mL/min and <60 mL/min by Cockcroft Gault equation adjusted for body weight~Adequate liver function~Exclusion Criteria:~Preexisting sensory neuropathy Grade ≥ 2 or motor neuropathy Grade ≥ 2~Uncontrolled central nervous system metastases~Use of any investigational drug within 14 days prior to the first dose of study drug~Any anticancer therapy, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol)~Subjects with Immunotherapy related adverse events requiring high doses of steroids (≥ 40 mg/day of prednisone) are not eligible~Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days prior to the first dose of study drug~History of thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) prior to the first dose of study drug~Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication~Known HIV or AIDS~Positive Hepatitis B surface antigen test~Positive Hepatitis C antibody test~Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy~Known sensitivity to any of the ingredients of the investigational product AGS15E~Major surgery within 28 days prior to first dose of study drug~History of a primary invasive malignancy not listed in the inclusion criteria, which has not been in remission for at least 3 years. The following are exempt from the 3 year limit:~Non-melanoma skin cancer;~adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is undetectable;~cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on Pap smear; and~definitively treated, stage I/II ER+ breast cancer~Active infection requiring treatment ≤ 7 days before first dose of study drug~History of uncontrolled diabetes mellitus or diabetic neuropathy~Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study~Has ocular conditions such as:~Active infection or corneal ulcer (e.g., keratitis)~Monocularity~History of corneal transplantation~Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)~Uncontrolled glaucoma (topical medications allowed)~Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder

18 Years

All

No

Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of adverse events | | up to 36 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Trough concentration (Ctrough) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of Anti-Drug Antibody (ADA) | | Up to 26 months | | Tumor response | Incidence of tumor response defined as either a complete response (CR) or partial response (PR) per RECIST criteria (version 1.1) that should be confirmed ≥ 28 days later | Up to 26 months | | Objective response rate | Defined as the percentage of subjects who experience a best response of either CR or PR in that cohort. CR and PR should be confirmed ≥ 28 days later | Up to 26 months | | Disease control rate | Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD) | Up to 26 months | | Progression free survival | Time from the date of first infusion to the earliest date of documented disease progression per radiological evidence or death from any cause | Up to 36 months | | Duration of response | Time from the date of the first response CR or PR to the earliest date of disease progression or death from any cause | Up to 36 months |

Metastatic Urothelial Cancer, AGS15E-13-1, ASG-15ME, Pharmacokinetics of AGS15E, AGS15E

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Part A: AGS-15E Dose Escalation (Dose Levels 1-6)<br>Subjects will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Additional subjects may be enrolled for expansion of these dose levels to further evaluate the safety and efficacy, as recommended by a data review team (DRT). | Drug: AGS15E<br>* intravenous (IV) infusion<br>| | Experimental: Part B: AGS-15E Cisplatin Therapy -ineligible Expansion<br>Urothelial subjects who have not received any prior lines of therapy an who are unfit for Cisplatin therapy (Cis-ineligible) will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Subjects will initially be dosed one dose level below the preliminary recommended phase 2 dose (RP2D). | Drug: AGS15E<br>* intravenous (IV) infusion<br>| | Experimental: Part C: AGS15E Immune Checkpoint Inhibitor Treated Expansion<br>Subjects previously treated with immune checkpoint inhibitors (CPI) in the metastatic setting will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Subjects will be dosed at the RP2D. | Drug: AGS15E<br>* intravenous (IV) infusion<br>| | Experimental: Part A: AGS15E Dose Expansion<br>Subjects will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. | Drug: AGS15E<br>* intravenous (IV) infusion<br>|

ASG-15ME is a Study of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer Study Overview ================= Brief Summary ----------------- The objectives of this study are to assess the safety, pharmacokinetics, immunogenicity and anti-tumor activity of AGS15E in subjects with metastatic urothelial cancer who failed at least one prior chemotherapy regimen for metastatic disease. Detailed Description ----------------- All subjects will receive a single intravenous infusion of AGS15E once weekly for 3 weeks of every 4 weeks. A cycle is 4 weeks. Subjects will continue treatment until disease progression, intolerability of AGS15E, investigator decision, or consent withdrawal. In subjects who discontinue therapy without documented disease progression and who still consent to study procedures, every effort should be made to continue monitoring their disease status by radiographic imaging until progression is documented, or new anticancer therapy, or death. All subjects will continue to be followed for survival until withdrawal of consent or study closure. If assessed as complete response (CR) or partial response (PR) per local review a confirmatory scan will be performed no less than 4 weeks from previous scan and preferably at week 5. Tumor imaging should also be performed whenever disease progression is suspected. Images will be sent to a central third party imaging vendor for an independent assessment per RECIST version 1.1. Although the imaging studies will be reviewed by a central third party imaging vendor in a retrospective fashion, all clinical decisions will be based on the interpretation of the investigator at the site treating the subject. Post-Treatment Follow-up Progression Free Survival: Subjects who discontinued study treatment for reasons other than radiographic disease progression will continue for a maximum of up to 12 months following the last dose of study drug until radiologically confirmed progression, initiation of a new anticancer therapy, death, loss to follow-up or withdraw consent for further follow-up, whichever of these events occurs first. The purpose of the post-treatment follow-up is to ascertain the duration of progression-free survival for all subjects enrolled in the study. Official Title ----------------- A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer Conditions ----------------- Metastatic Urothelial Cancer Intervention / Treatment ----------------- * Drug: AGS15E Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible. Part A: Subject must have failed at least one prior chemotherapy regimen for metastatic disease and/or is unfit for cisplatin-based chemotherapy. Part B: Subject must not have received any prior lines of chemotherapy in the metastatic setting (prior treatment with immunotherapy is allowed). Part C (CPI-Treated Expansion): Subject must have received prior treatment with a CPI in the metastatic setting Subjects must have measureable disease according to RECIST (version 1.1). Part A and C: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Part B: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 Life expectancy of ≥ 3 months Adequate hematologic function Parts A and C: Renal function, as follows: serum creatinine ≤ 2.0 mg/dL, or measured 24 hour creatinine clearance of ≥ 45 mL/min Part B: Renal function, as follows: creatinine clearance estimate ≥ 15 mL/min and <60 mL/min by Cockcroft Gault equation adjusted for body weight Adequate liver function Exclusion Criteria: Preexisting sensory neuropathy Grade ≥ 2 or motor neuropathy Grade ≥ 2 Uncontrolled central nervous system metastases Use of any investigational drug within 14 days prior to the first dose of study drug Any anticancer therapy, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol) Subjects with Immunotherapy related adverse events requiring high doses of steroids (≥ 40 mg/day of prednisone) are not eligible Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days prior to the first dose of study drug History of thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) prior to the first dose of study drug Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication Known HIV or AIDS Positive Hepatitis B surface antigen test Positive Hepatitis C antibody test Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy Known sensitivity to any of the ingredients of the investigational product AGS15E Major surgery within 28 days prior to first dose of study drug History of a primary invasive malignancy not listed in the inclusion criteria, which has not been in remission for at least 3 years. The following are exempt from the 3 year limit: Non-melanoma skin cancer; adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is undetectable; cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on Pap smear; and definitively treated, stage I/II ER+ breast cancer Active infection requiring treatment ≤ 7 days before first dose of study drug History of uncontrolled diabetes mellitus or diabetic neuropathy Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study Has ocular conditions such as: Active infection or corneal ulcer (e.g., keratitis) Monocularity History of corneal transplantation Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration) Uncontrolled glaucoma (topical medications allowed) Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Part A: AGS-15E Dose Escalation (Dose Levels 1-6)<br>Subjects will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Additional subjects may be enrolled for expansion of these dose levels to further evaluate the safety and efficacy, as recommended by a data review team (DRT). | Drug: AGS15E<br>* intravenous (IV) infusion<br>| | Experimental: Part B: AGS-15E Cisplatin Therapy -ineligible Expansion<br>Urothelial subjects who have not received any prior lines of therapy an who are unfit for Cisplatin therapy (Cis-ineligible) will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Subjects will initially be dosed one dose level below the preliminary recommended phase 2 dose (RP2D). | Drug: AGS15E<br>* intravenous (IV) infusion<br>| | Experimental: Part C: AGS15E Immune Checkpoint Inhibitor Treated Expansion<br>Subjects previously treated with immune checkpoint inhibitors (CPI) in the metastatic setting will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Subjects will be dosed at the RP2D. | Drug: AGS15E<br>* intravenous (IV) infusion<br>| | Experimental: Part A: AGS15E Dose Expansion<br>Subjects will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. | Drug: AGS15E<br>* intravenous (IV) infusion<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of adverse events | | up to 36 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Trough concentration (Ctrough) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | | Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss) | | Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of Anti-Drug Antibody (ADA) | | Up to 26 months | | Tumor response | Incidence of tumor response defined as either a complete response (CR) or partial response (PR) per RECIST criteria (version 1.1) that should be confirmed ≥ 28 days later | Up to 26 months | | Objective response rate | Defined as the percentage of subjects who experience a best response of either CR or PR in that cohort. CR and PR should be confirmed ≥ 28 days later | Up to 26 months | | Disease control rate | Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD) | Up to 26 months | | Progression free survival | Time from the date of first infusion to the earliest date of documented disease progression per radiological evidence or death from any cause | Up to 36 months | | Duration of response | Time from the date of the first response CR or PR to the earliest date of disease progression or death from any cause | Up to 36 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Metastatic Urothelial Cancer, AGS15E-13-1, ASG-15ME, Pharmacokinetics of AGS15E, AGS15E

NCT03473574

Durvalumab and Tremelimumab With Gemcitabine or Gemcitabine/Cisplatin Compared to Gemcitabine/Cisplatin in CCA Patients

To determine the efficacy in terms of objective response rate (ORR) of the combination of durvalumab and tremelimumab in addition with gemcitabine or in addition with gemcitabine and cisplatin in treatment-naïve patients with advanced, unresectable and/or metastatic cholangio- and gallbladder carcinoma (CCA).

Patients with CCA have poor outcomes, as a consequence of the very aggressive nature of the disease, and the limited treatment options. Thus there is a significant unmet medical need for additional treatment options for use in this patient population. As in most other tumor entities however, only a fraction of patients respond to immunotherapy alone. Evidence suggests that those patients might preferentially have tumors that have favorable mutational landscapes, express the PD-L1 and/ or contain preexisting tumor-infiltrating CD8+ T cells that are inhibited locally, e.g., by PD-1 engagement. In order to increase the proportion of patients who could ultimately benefit from immunotherapies, it is important to develop strategies that can be employed for converting tumor microenvironments lacking T cell infiltration to ones displaying antitumor T-cell immunity and therefore to sensitize tumors to checkpoint inhibition therapy. Therefore, the aim of this study is to determine the combination of durvalumab and tremelimumab in addition with gemcitabine or in addition with gemcitabine and cisplatin in treatment-naïve patients with advanced, unresectable and/or metastatic cholangio- and gallbladder carcinoma.

A Randomized Phase II Trial of Durvalumab and Tremelimumab With Gemcitabine or Gemcitabine and Cisplatin Compared to Gemcitabine and Cisplatin in Treatment-naïve Patients With Cholangio- and Gallbladder Carcinoma (IMMUCHEC)

Cholangiocarcinoma, Gall Bladder Carcinoma, Cholangiocarcinoma Non-resectable, Gallbladder Carcinoma Non-Resectable

* Biological: Durvalumab * Drug: Gemcitabine * Drug: Cisplatin * Biological: Tremelimumab

Inclusion Criteria:~Fully-informed written consent and locally required authorization (European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.~Age ≥ 18 years.~Histologically documented diagnosis of cholangiocarcinoma or gall bladder carcinoma and available tumor tissue (block or at least 4 slides) for translational research.~Performance status (PS) ≤ 1(ECOG scale).~At least one measurable site of disease as defined by RECISTv1.1 criteria.~Adequate bone marrow and renal function including the following: Hemoglobin~≥ 9.0 g/dL; absolute neutrophil count ≥ 1.5 x 10^9/L; platelets ≥ 100 x 10^9 /L; Creatinine ≤ 1.5 x upper normal limit.~Calculated creatinine clearance ≥40 mL/min as determined by the Cockcroft- Gault equation (using actual body weight)~Adequate hepatic function (with stenting for any obstruction, if required) including the following: Total bilirubin ≤ 2x upper normal limit; AST (SGOT), ALT (SGPT) ≤ 5 x upper normal limit; prothrombin time ≥ 60%; albumin ≥ 30 g/L.~Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.~Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:~Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).~Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).~The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.~Exclusion Criteria:~Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study~Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.~Prior immunotherapy or use of other investigational agents, including prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte associated antigen-4 (anti-CTLA-4) antibody, therapeutic cancer vaccines.~Prior chemotherapy with gemcitabine, Cisplatin and/or capecitabine (exception: gemcitabine, cisplatind and/or capecitabine in the adjuvant setting, last infusion has to be ≥ 6 months prior randomization).~Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria~Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.~Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.~Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. Note: Local treatment of isolated lesions for palliative intent is acceptable (eg, local radiotherapy).~Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drugs.~Major surgery (as defined by the Investigator) within 4 weeks prior to the first dose of the investigational product (IMP) of starting the study and patients must have recovered from effects of major surgery. Note: Local non-major surgery for palliative intent (eg, surgery of isolated lesions, per-cutaneous biliary drainage or biliary stenting) is acceptable.~History of allogenic organ transplantation.~Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).~The following are exceptions to this criterion:~Patients with vitiligo or alopecia~Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement~Any chronic skin condition that does not require systemic therapy~Patients without active disease in the last 5 years may be included but only after consultation with the study physician~Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent~History of another primary malignancy except for:~Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IMP and of low potential risk for recurrence~Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease~Adequately treated carcinoma in situ without evidence of disease~History of leptomeningeal carcinomatosis~Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT/ MRI of the brain prior to study entry.~History of active primary immunodeficiency~Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg) result], hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.~Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:~Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)~Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent~Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP.~Note: Patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 30 days after the last dose of IMP. 19. Body weight ≤30 kg. 20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of tremelimumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy. 21. Known allergy or hypersensitivity to any of the IMPs or any of the constituents of the product. 22. Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment. 23. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG. 25. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Treatment Arm A: Combination of Durvalumab, Tremelimumab (Regimen 1) and Gemcitabine Treatment Arm B: Combination of Durvalumab, Tremelimumab (Regimen 1), Gemcitabine and Cisplatin Treatment Arm C: Gemcitabine and Cisplatin Treatment Arm D: Combination of Durvalumab, Tremelimumab (Regimen 2), Gemcitabine and Cisplatin Treatment Arm E: Combination of Durvalumab, Gemcitabine and Cisplatin Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Objective response rate (ORR) | Response Rate (RR) according to RECIST V1.1 | 30 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall survival (OS) | Efficacy of the combination of durvalumab and tremelimumab in addition with gemcitabine or in addition with gemcitabine and cisplatin in treatment naïve patients with advanced, unresectable and/or metastatic cholangio- and gallbladder carcinoma | max observation period 30 months | | Incidence of Treatment Emergent Adverse Events as assessed by NCI CTCAE V4.0 (Safety and Tolerability) | Data will be obtained on vital signs, clinical parameters and feasibility of the regimen | 30 months | | Quality of Life | EORTC-QLQ-C30 (European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire 30 items) Version 3.0. The QLQ-C30 is composed of multi-item scales and single-item measures, including fiveAll of the scales and single-item measures have a score range from 0 to 100. A high score shows a high response level. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems functional scales, three symptom scales, a global health status / QoL scale, and six single items. | 30 months |

Gemcitabine, Durvalumab, Tremelimumab, Antineoplastic Agents, Antimetabolites, Antineoplastic, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Immunological

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Arm A<br>Durvalumab in combination with Tremelimumab (Regimen 1) and Gemcitabine | Biological: Durvalumab<br>* immune checkpoint inhibitor<br>Drug: Gemcitabine<br>* standard chemotherapy<br>Biological: Tremelimumab<br>* immune checkpoint inhibitor<br>| | Experimental: Arm B<br>Durvalumab in combination with Tremelimumab (Regimen 1), Gemcitabine and Cisplatin | Biological: Durvalumab<br>* immune checkpoint inhibitor<br>Drug: Gemcitabine<br>* standard chemotherapy<br>Drug: Cisplatin<br>* standard chemotherapy<br>Biological: Tremelimumab<br>* immune checkpoint inhibitor<br>| | Other: Arm C<br>Gemcitabine in combination with Cisplatin | Drug: Gemcitabine<br>* standard chemotherapy<br>Drug: Cisplatin<br>* standard chemotherapy<br>| | Experimental: Arm D<br>Durvalumab in combination with Tremelimumab (Regimen 2), Gemcitabine and Cisplatin | Biological: Durvalumab<br>* immune checkpoint inhibitor<br>Drug: Gemcitabine<br>* standard chemotherapy<br>Drug: Cisplatin<br>* standard chemotherapy<br>Biological: Tremelimumab<br>* immune checkpoint inhibitor<br>| | Experimental: Arm E<br>Durvalumab in combination with Gemcitabine and Cisplatin | Biological: Durvalumab<br>* immune checkpoint inhibitor<br>Drug: Gemcitabine<br>* standard chemotherapy<br>Drug: Cisplatin<br>* standard chemotherapy<br>|

Durvalumab and Tremelimumab With Gemcitabine or Gemcitabine/Cisplatin Compared to Gemcitabine/Cisplatin in CCA Patients Study Overview ================= Brief Summary ----------------- To determine the efficacy in terms of objective response rate (ORR) of the combination of durvalumab and tremelimumab in addition with gemcitabine or in addition with gemcitabine and cisplatin in treatment-naïve patients with advanced, unresectable and/or metastatic cholangio- and gallbladder carcinoma (CCA). Detailed Description ----------------- Patients with CCA have poor outcomes, as a consequence of the very aggressive nature of the disease, and the limited treatment options. Thus there is a significant unmet medical need for additional treatment options for use in this patient population. As in most other tumor entities however, only a fraction of patients respond to immunotherapy alone. Evidence suggests that those patients might preferentially have tumors that have favorable mutational landscapes, express the PD-L1 and/ or contain preexisting tumor-infiltrating CD8+ T cells that are inhibited locally, e.g., by PD-1 engagement. In order to increase the proportion of patients who could ultimately benefit from immunotherapies, it is important to develop strategies that can be employed for converting tumor microenvironments lacking T cell infiltration to ones displaying antitumor T-cell immunity and therefore to sensitize tumors to checkpoint inhibition therapy. Therefore, the aim of this study is to determine the combination of durvalumab and tremelimumab in addition with gemcitabine or in addition with gemcitabine and cisplatin in treatment-naïve patients with advanced, unresectable and/or metastatic cholangio- and gallbladder carcinoma. Official Title ----------------- A Randomized Phase II Trial of Durvalumab and Tremelimumab With Gemcitabine or Gemcitabine and Cisplatin Compared to Gemcitabine and Cisplatin in Treatment-naïve Patients With Cholangio- and Gallbladder Carcinoma (IMMUCHEC) Conditions ----------------- Cholangiocarcinoma, Gall Bladder Carcinoma, Cholangiocarcinoma Non-resectable, Gallbladder Carcinoma Non-Resectable Intervention / Treatment ----------------- * Biological: Durvalumab * Drug: Gemcitabine * Drug: Cisplatin * Biological: Tremelimumab Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Fully-informed written consent and locally required authorization (European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. Age ≥ 18 years. Histologically documented diagnosis of cholangiocarcinoma or gall bladder carcinoma and available tumor tissue (block or at least 4 slides) for translational research. Performance status (PS) ≤ 1(ECOG scale). At least one measurable site of disease as defined by RECISTv1.1 criteria. Adequate bone marrow and renal function including the following: Hemoglobin ≥ 9.0 g/dL; absolute neutrophil count ≥ 1.5 x 10^9/L; platelets ≥ 100 x 10^9 /L; Creatinine ≤ 1.5 x upper normal limit. Calculated creatinine clearance ≥40 mL/min as determined by the Cockcroft- Gault equation (using actual body weight) Adequate hepatic function (with stenting for any obstruction, if required) including the following: Total bilirubin ≤ 2x upper normal limit; AST (SGOT), ALT (SGPT) ≤ 5 x upper normal limit; prothrombin time ≥ 60%; albumin ≥ 30 g/L. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations. Exclusion Criteria: Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment. Prior immunotherapy or use of other investigational agents, including prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte associated antigen-4 (anti-CTLA-4) antibody, therapeutic cancer vaccines. Prior chemotherapy with gemcitabine, Cisplatin and/or capecitabine (exception: gemcitabine, cisplatind and/or capecitabine in the adjuvant setting, last infusion has to be ≥ 6 months prior randomization). Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician. Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. Note: Local treatment of isolated lesions for palliative intent is acceptable (eg, local radiotherapy). Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drugs. Major surgery (as defined by the Investigator) within 4 weeks prior to the first dose of the investigational product (IMP) of starting the study and patients must have recovered from effects of major surgery. Note: Local non-major surgery for palliative intent (eg, surgery of isolated lesions, per-cutaneous biliary drainage or biliary stenting) is acceptable. History of allogenic organ transplantation. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: Patients with vitiligo or alopecia Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the study physician Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IMP and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease History of leptomeningeal carcinomatosis Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT/ MRI of the brain prior to study entry. History of active primary immunodeficiency Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg) result], hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 30 days after the last dose of IMP. 19. Body weight ≤30 kg. 20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of tremelimumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy. 21. Known allergy or hypersensitivity to any of the IMPs or any of the constituents of the product. 22. Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment. 23. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG. 25. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG]. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Treatment Arm A: Combination of Durvalumab, Tremelimumab (Regimen 1) and Gemcitabine Treatment Arm B: Combination of Durvalumab, Tremelimumab (Regimen 1), Gemcitabine and Cisplatin Treatment Arm C: Gemcitabine and Cisplatin Treatment Arm D: Combination of Durvalumab, Tremelimumab (Regimen 2), Gemcitabine and Cisplatin Treatment Arm E: Combination of Durvalumab, Gemcitabine and Cisplatin Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Arm A<br>Durvalumab in combination with Tremelimumab (Regimen 1) and Gemcitabine | Biological: Durvalumab<br>* immune checkpoint inhibitor<br>Drug: Gemcitabine<br>* standard chemotherapy<br>Biological: Tremelimumab<br>* immune checkpoint inhibitor<br>| | Experimental: Arm B<br>Durvalumab in combination with Tremelimumab (Regimen 1), Gemcitabine and Cisplatin | Biological: Durvalumab<br>* immune checkpoint inhibitor<br>Drug: Gemcitabine<br>* standard chemotherapy<br>Drug: Cisplatin<br>* standard chemotherapy<br>Biological: Tremelimumab<br>* immune checkpoint inhibitor<br>| | Other: Arm C<br>Gemcitabine in combination with Cisplatin | Drug: Gemcitabine<br>* standard chemotherapy<br>Drug: Cisplatin<br>* standard chemotherapy<br>| | Experimental: Arm D<br>Durvalumab in combination with Tremelimumab (Regimen 2), Gemcitabine and Cisplatin | Biological: Durvalumab<br>* immune checkpoint inhibitor<br>Drug: Gemcitabine<br>* standard chemotherapy<br>Drug: Cisplatin<br>* standard chemotherapy<br>Biological: Tremelimumab<br>* immune checkpoint inhibitor<br>| | Experimental: Arm E<br>Durvalumab in combination with Gemcitabine and Cisplatin | Biological: Durvalumab<br>* immune checkpoint inhibitor<br>Drug: Gemcitabine<br>* standard chemotherapy<br>Drug: Cisplatin<br>* standard chemotherapy<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Objective response rate (ORR) | Response Rate (RR) according to RECIST V1.1 | 30 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall survival (OS) | Efficacy of the combination of durvalumab and tremelimumab in addition with gemcitabine or in addition with gemcitabine and cisplatin in treatment naïve patients with advanced, unresectable and/or metastatic cholangio- and gallbladder carcinoma | max observation period 30 months | | Incidence of Treatment Emergent Adverse Events as assessed by NCI CTCAE V4.0 (Safety and Tolerability) | Data will be obtained on vital signs, clinical parameters and feasibility of the regimen | 30 months | | Quality of Life | EORTC-QLQ-C30 (European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire 30 items) Version 3.0. The QLQ-C30 is composed of multi-item scales and single-item measures, including fiveAll of the scales and single-item measures have a score range from 0 to 100. A high score shows a high response level. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems functional scales, three symptom scales, a global health status / QoL scale, and six single items. | 30 months |

NCT03568734

Cesarean Section and Intestinal Flora of the Newborn

Mode of delivery affects gut microbiome of the infant. Infants born by caesarean section have a less heterogenous microbiome for the first weeks of life. This has been associated with an increased risk for atopy-related diseases, such as allergy and asthma. In this proof-of-principle study the investigators evaluate whether an orally delivered maternal fecal transplant to the infant during the first hours of life affects gut microbiome of the infant

Background~The immune system is affected by the colonizing microbiome. The gut microbiome has been associated with a multitude of inflammatory diseases, such as the development of autoimmune diseases. The association between microbiome and allergic diseases, asthma, type I diabetes and inflammatory bowel diseases have been demonstrated. Moreover, changes in gut microbiome during the first weeks of life have been associated with the development of atopy.~Already at birth, a low concentration of bacteria is present in the meconium of the vaginally delivered infant. Although the neonatal stool is not fully sterile, colonization of the intestinal tract takes place at delivery and throughout the first years of life. The gut microbiome of infants delivered vaginally (VD) and by cesarean section (CS) differs markedly from each other and this difference persists throughout the first years of life. The gut microbiome of infants born by CS have a lower total microbiota diversity and lower Th1 response than those born by VD. Infants delivered by CS been shown to be more likely to develop chronic inflammatory and allergic diseases, eg. inflammatory bowel disease, and systemic connective disorders, and asthma than those delivered vaginally.~Partial restoration of the microbiota of CS-infants was seen when introduced with vaginal microbial transfer. However, the vaginal microbiome is very limited to mainly Lactobacillus spp. and does not contain the microbes that are abundant in the gut microbiota of the mother. Fecal transplantation, or intestinal microbiota transfer, is used to treat chronic infections of Clostridium difficile. However, fecal transplantation has not been used to compensate for the low diversity of CS infants. In this pilot, proof-of-concept and safety evaluation study, the researchers aim to assess the feasibility of fecal transplantation after birth in infants delivered by CS.

Cesarean Section and Intestinal Flora of the Newborn

Intestinal Microbiome

* Other: Fecal transplant

Inclusion criteria:~healthy pregnancy~planned cesarean section delivery~Exclusion criteria:~Maternal exclusion criteria:~positive GBS status~maternal refusal~maternal antibiotic treatment within the last 3 months~any travel outside of European Union within the last 3 months~multiple pregnancy and CS after the onset of labor (non-elective CS)~Infant exclusion criteria:~Apgar score of less than 8~disturbances of neonatal adaptation (such as transient tachypnea of the newborn)~antibiotic treatment of the newborn before discharge

Female

Accepts Healthy Volunteers

Primary Purpose: Prevention Intervention Model: Single Group Assignment Interventional Model Description: 12 mothers participating in the study (due for caesarean section) are screened for transmissible diseases. A transplant sample is gathered from the mother, processed, and given to the infant at delivery by caesarean section. Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of Treatment-Emergent Adverse Events | Clinical condition, inflammatory markers | 0-3 postnatal days |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Attachment of transplant | Evaluation of microbiome in comparison to transplant from samples taken from infants weekly at 1-4 weeks of life and at 3 months of age. | 1 to 12 weeks of age |

microbiome, transplant, infant, newborn

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Transplant arm<br>Fecal transplant sample given to child at delivery | Other: Fecal transplant<br>* At delivery, i.e. 39-40 weeks of gestation, the newborn infant is given 0.1 g maternal fecal sample (in 0.5 ml of the isotonic saline+10 % glycerol) dissolved in 10 ml of bank milk orally. The sample is given within 2 h of birth. Milk containing fecal sample (2 ml) is given as a part of a total feeding of 5-10 ml.<br>|

Cesarean Section and Intestinal Flora of the Newborn Study Overview ================= Brief Summary ----------------- Mode of delivery affects gut microbiome of the infant. Infants born by caesarean section have a less heterogenous microbiome for the first weeks of life. This has been associated with an increased risk for atopy-related diseases, such as allergy and asthma. In this proof-of-principle study the investigators evaluate whether an orally delivered maternal fecal transplant to the infant during the first hours of life affects gut microbiome of the infant Detailed Description ----------------- Background The immune system is affected by the colonizing microbiome. The gut microbiome has been associated with a multitude of inflammatory diseases, such as the development of autoimmune diseases. The association between microbiome and allergic diseases, asthma, type I diabetes and inflammatory bowel diseases have been demonstrated. Moreover, changes in gut microbiome during the first weeks of life have been associated with the development of atopy. Already at birth, a low concentration of bacteria is present in the meconium of the vaginally delivered infant. Although the neonatal stool is not fully sterile, colonization of the intestinal tract takes place at delivery and throughout the first years of life. The gut microbiome of infants delivered vaginally (VD) and by cesarean section (CS) differs markedly from each other and this difference persists throughout the first years of life. The gut microbiome of infants born by CS have a lower total microbiota diversity and lower Th1 response than those born by VD. Infants delivered by CS been shown to be more likely to develop chronic inflammatory and allergic diseases, eg. inflammatory bowel disease, and systemic connective disorders, and asthma than those delivered vaginally. Partial restoration of the microbiota of CS-infants was seen when introduced with vaginal microbial transfer. However, the vaginal microbiome is very limited to mainly Lactobacillus spp. and does not contain the microbes that are abundant in the gut microbiota of the mother. Fecal transplantation, or intestinal microbiota transfer, is used to treat chronic infections of Clostridium difficile. However, fecal transplantation has not been used to compensate for the low diversity of CS infants. In this pilot, proof-of-concept and safety evaluation study, the researchers aim to assess the feasibility of fecal transplantation after birth in infants delivered by CS. Official Title ----------------- Cesarean Section and Intestinal Flora of the Newborn Conditions ----------------- Intestinal Microbiome Intervention / Treatment ----------------- * Other: Fecal transplant Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria: healthy pregnancy planned cesarean section delivery Exclusion criteria: Maternal exclusion criteria: positive GBS status maternal refusal maternal antibiotic treatment within the last 3 months any travel outside of European Union within the last 3 months multiple pregnancy and CS after the onset of labor (non-elective CS) Infant exclusion criteria: Apgar score of less than 8 disturbances of neonatal adaptation (such as transient tachypnea of the newborn) antibiotic treatment of the newborn before discharge Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Intervention Model: Single Group Assignment Interventional Model Description: 12 mothers participating in the study (due for caesarean section) are screened for transmissible diseases. A transplant sample is gathered from the mother, processed, and given to the infant at delivery by caesarean section. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Transplant arm<br>Fecal transplant sample given to child at delivery | Other: Fecal transplant<br>* At delivery, i.e. 39-40 weeks of gestation, the newborn infant is given 0.1 g maternal fecal sample (in 0.5 ml of the isotonic saline+10 % glycerol) dissolved in 10 ml of bank milk orally. The sample is given within 2 h of birth. Milk containing fecal sample (2 ml) is given as a part of a total feeding of 5-10 ml.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of Treatment-Emergent Adverse Events | Clinical condition, inflammatory markers | 0-3 postnatal days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Attachment of transplant | Evaluation of microbiome in comparison to transplant from samples taken from infants weekly at 1-4 weeks of life and at 3 months of age. | 1 to 12 weeks of age | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- microbiome, transplant, infant, newborn

NCT06063278

Step by Step Group Therapy for Bulimia Nervosa: Effectiveness and Mechanisms of Change.

This a pseudo-randomized clinical trial that examines if a specific group therapy for BN is effective in improving its symptomatology, and what variables mediate such improvements. To do so a sample of 100 patients with BN will be pseudorandomized in a Group Therapy for BN or in a control waiting list group. Patients will be assessed at baseline, at the end of the group therapy and at 2 year follow up.

This is a controlled non randomized study that will compare a group of patients with BN that participate in the SBS group therapy with a group of BN patients who will be in wait list as a control condition.~Patients for this single center trial will be recruited from the outpatient facility of the Hospital de la Santa Creu I Sant Pau (Barcelona, Spain).~After assessed for eligibility participants will be given a set of self -report questionnaires. After the questionnaires are completed participants will be allocated to wait list condition or to the treatment arm. Time between assessment and starting the SBS group will be a month or least. Participants will be administered the same questionnaires the following month after finishing the treatment or after 3 to 4 months after the first assessment for the control condition.

Step by Step Group Therapy for Bulimia Nervosa: Effectiveness and Mechanisms of Change.

Bulimia Nervosa

* Behavioral: l Group Therapy for BN.

Inclusion Criteria:~Diagnostic of Bulimia Nervosa~Exclusion Criteria:~Not understanding Spanish or Catalan Language

18 Years

65 Years

All

No

Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Eating Attitudes Test, E-40. | A self report questionarie that assesses eating disorder symptomatology. The range of scores is 0-78. Higher scores mean higher eating disorders sympthoms. | 3 months | | Eating Disorder Inventory, EDI | A self report questionarie that assesses eating disorder symptomatology. The range of scores is 0-192. Higher scores mean higher eating disorders sympthoms | 3 months | | Bulimic Investigatory Test Edinburgh, BITE | A self report questionarie that assesses bulimia nervosa symptomatology.The range of scores is 0-30. Higher scores mean higher bulimic sympthoms | 3 months | | Body Shape Questionnaire, BSQ-34 | A self report questionarie that assesses eating disorder symptomatology. The score is ranging between 34-204 points. Higher scores point to an increased level of concern on body shape. | 3 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Working alliance Inventory -short, WAIS. | A self report questionarie that assesses bulimia nervosa symptomatology. Values range from 12 to 84. Hihger scores meaning higher therapeutic alliance. | 3 months | | Autism-Spectrum Quotient, AQ | A self report questionarie that assesses autistic traits. The range of scores is 0 to 50. Higher scores mean higher autistic traits. | 3 months | | Quality of Life Enjoyment and Satisfaction Questionnaire, Q-LES-Q. | A self report questionarie that assesses quality of life. The range of scores is 0-100. Higher scores mean higher quality of life. | 3 months | | Beck Depression Inventory, BDI-II | A self report questionarie that assesses depressive symptoatology. The range of scores is 0-83. Higher scores mean higher depressive symptoms. | 3 months | | Rosenberg Self-Esteem Scale, RSE. | A self report questionarie that assesses self steem. The scale ranges from 0-30. Higher scores mean higher self-esteem. The range scores is 0-60. | 3 months | | State -Trait Anxiety Inventory, STAI. | A self report questionarie that assesses anxiety. Higher scores mean higher anxiety. | 3 months | | Difficulties in Emotion Regulation Scale (DERS). | A self report questionarie that assesses emotion regulation difficulties. The scale ranges from 28-40. H igher scores indicate more difficulty in emotion regulation. | 3 months |

Bulimia, Bulimia Nervosa, Hyperphagia, Signs and Symptoms, Digestive, Feeding and Eating Disorders, Mental Disorders

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: BN Group<br>Patients will take part of a Therapeutic BN Group | Behavioral: l Group Therapy for BN.<br>* 9 to 10 group sessions of 90 to 120min each<br>| | No Intervention: Waiting List<br>Participants will be in the waiting list. | |

Step by Step Group Therapy for Bulimia Nervosa: Effectiveness and Mechanisms of Change. Study Overview ================= Brief Summary ----------------- This a pseudo-randomized clinical trial that examines if a specific group therapy for BN is effective in improving its symptomatology, and what variables mediate such improvements. To do so a sample of 100 patients with BN will be pseudorandomized in a Group Therapy for BN or in a control waiting list group. Patients will be assessed at baseline, at the end of the group therapy and at 2 year follow up. Detailed Description ----------------- This is a controlled non randomized study that will compare a group of patients with BN that participate in the SBS group therapy with a group of BN patients who will be in wait list as a control condition. Patients for this single center trial will be recruited from the outpatient facility of the Hospital de la Santa Creu I Sant Pau (Barcelona, Spain). After assessed for eligibility participants will be given a set of self -report questionnaires. After the questionnaires are completed participants will be allocated to wait list condition or to the treatment arm. Time between assessment and starting the SBS group will be a month or least. Participants will be administered the same questionnaires the following month after finishing the treatment or after 3 to 4 months after the first assessment for the control condition. Official Title ----------------- Step by Step Group Therapy for Bulimia Nervosa: Effectiveness and Mechanisms of Change. Conditions ----------------- Bulimia Nervosa Intervention / Treatment ----------------- * Behavioral: l Group Therapy for BN. Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Diagnostic of Bulimia Nervosa Exclusion Criteria: Not understanding Spanish or Catalan Language Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: BN Group<br>Patients will take part of a Therapeutic BN Group | Behavioral: l Group Therapy for BN.<br>* 9 to 10 group sessions of 90 to 120min each<br>| | No Intervention: Waiting List<br>Participants will be in the waiting list. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Eating Attitudes Test, E-40. | A self report questionarie that assesses eating disorder symptomatology. The range of scores is 0-78. Higher scores mean higher eating disorders sympthoms. | 3 months | | Eating Disorder Inventory, EDI | A self report questionarie that assesses eating disorder symptomatology. The range of scores is 0-192. Higher scores mean higher eating disorders sympthoms | 3 months | | Bulimic Investigatory Test Edinburgh, BITE | A self report questionarie that assesses bulimia nervosa symptomatology.The range of scores is 0-30. Higher scores mean higher bulimic sympthoms | 3 months | | Body Shape Questionnaire, BSQ-34 | A self report questionarie that assesses eating disorder symptomatology. The score is ranging between 34-204 points. Higher scores point to an increased level of concern on body shape. | 3 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Working alliance Inventory -short, WAIS. | A self report questionarie that assesses bulimia nervosa symptomatology. Values range from 12 to 84. Hihger scores meaning higher therapeutic alliance. | 3 months | | Autism-Spectrum Quotient, AQ | A self report questionarie that assesses autistic traits. The range of scores is 0 to 50. Higher scores mean higher autistic traits. | 3 months | | Quality of Life Enjoyment and Satisfaction Questionnaire, Q-LES-Q. | A self report questionarie that assesses quality of life. The range of scores is 0-100. Higher scores mean higher quality of life. | 3 months | | Beck Depression Inventory, BDI-II | A self report questionarie that assesses depressive symptoatology. The range of scores is 0-83. Higher scores mean higher depressive symptoms. | 3 months | | Rosenberg Self-Esteem Scale, RSE. | A self report questionarie that assesses self steem. The scale ranges from 0-30. Higher scores mean higher self-esteem. The range scores is 0-60. | 3 months | | State -Trait Anxiety Inventory, STAI. | A self report questionarie that assesses anxiety. Higher scores mean higher anxiety. | 3 months | | Difficulties in Emotion Regulation Scale (DERS). | A self report questionarie that assesses emotion regulation difficulties. The scale ranges from 28-40. H igher scores indicate more difficulty in emotion regulation. | 3 months |

NCT03201354

Efficacy and Safety of the ExPRESS Implant Versus Deep Sclerectomy in Combined Surgery

The Ex-PRESS Glaucoma Filtration Device is a small, non-valved implant that was designed to lower intraocular pressure (IOP) by shunting aqueous humor from the anterior chamber into the subconjunctival space. The implant was developed in response to the need for more straightforward, standardized and safe surgical technique than standard filtration surgery. No iridectomy and no sclerectomy is needed if an Ex-PRESS device is implanted under a partial-thickness scleral flap. This may reduce surgical time and complications when compared to a standard trabeculectomy.~In some studies it has been found to be safe and effective with few complications, even in high-risk patients. No previous studies have compared filtration surgery with Ex-Press implant to deep sclerectomy.

Hypothesis:~In combined procedure (cataract and filtering surgery), the effect of Ex-PRESS device has similar efficacy reducing intraocular pressure than non penetrant deep sclerectomy and with good level of safety.~Objective:~To evaluate and compare the efficacy and safety at 12 months of the filtering surgery with the Ex-PRESS device with that of deep sclerectomy.~Methods:~Design: Multi-center, prospective, simple-blind, randomized study.~Primary variable:~1. Intraocular pressure.~Secondary variables:~Success rate at IOP <18~Frequency and type of complications~Number of hypotensive drugs needed.~Sample size calculation: Accepting an alfa risk of 0.05 and a beta risk of 0.20 in a two-sided Student's T-test, 50 subjects are necessary in first group and 50 in the second to recognize as statistically significant a difference greater than or equal to 10% in IOP, with a common standard deviation of 17%. A drop-out rate of 8% has been anticipated. If no drop-out rate is considered, the number of needed subjects is 92 (46 per group).~If the drop out rate is more than 8%:~If the recruitment period is open, another subjects will be included.~If the recruitment period os close, the inclusion of another subject will be evaluated to maintain the statistic power of the study.~Method~-Single blinded. Each patient will be assigned to one of the two arms (Ex-PRESS or Deep sclerectomy) the same day of surgery. The surgeon will be informed of the randomization result just before surgery by the study coordinator.~Pre-operative examinations:~History summarizing previous surgical procedures, intraocular pressure while on treatment, target pressure at the discretion of the surgeon, visual field (SITA standard 24-2), gonioscopy, and a detailed description of the optic disc / nerve fiber layer by a glaucoma specialist was performed in all subjects included.~Post-operative examinations~Visits were undertaken at 1 day, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, and 12 months.~Tests:~visual fields (month 12)~gonioscopy (month 12)~intraocular pressure (all visits)~optic disc examination (all visits, under dilation at 3 and 12 month)~Pachymetry (preop exam)~endothelial cell count (months 3 and 12)~Bleb morphology (month 1 and 12)~methodic registration of complications (all visits)~A specific CRF was designed with all variables and data required for the study which included a long list of individual potential complications~Pre-operative treatment. Prostaglandin analogues will be discontinued one week before surgery, but the rest of hypotensive drugs will be maintained until the day of surgery~Surgery. Each patient was assigned to one of the two arms (Ex-PRESS or Deep sclerectomy) the same day of surgery. The surgeon wil be informed of the randomization result just before surgery by the study coordinator.~The surgical technique is as follows: retro/peribulbar o subtenon's anesthesia, superior rectus or corneal traction suture, phacoemulsification through 2.1 to 2.8 mm incision with IOL implantation, a fornix-based conjunctival flap, sufficient but not excessive cauterization, application MMC 0,2 mg/ml for 2 minutes under the conjunctiva, then MMC was washed out with 50 ml of saline solution, then and according to the randomization result a scleral flap (5x5 mm in the NPDS, 4x4 mm in the Ex-Press group) is dissected.~Group 1. Then the Ex-PRESS device was placed according to the manufacturer's instructions and its position in the anterior chamber was verified by the surgeon.~Group 2. Deep sclerectomy (NPDS) was performed by dissecting a Deep scleral flap (4x4 mm) and peeling the trabeculo-descement membrane. A Esnoper (AJL, Vitoria, Spain) device was positioned under the external scleral flap and fixated with a 10/0 nylon suture.~Suture Nylon 10/00 suture was used to place four or five stitches in the Ex-Press group and 2 stitches in the NPDS group. Then a hermetic conjunctival suture was performed at the limbus with 10/0 nylon.~Post-operative treatment. All patients instilled Moxifloxacin Antibiotic every 6 hours for 1 week, Dexamethasone (every 2 hours for 1 month, every 4-6 hours on the second month and gradually tapered on the third month according to surgeon's instructions). Atropine was also used at the discretion of the surgeon when clinical finds recommended its use.~Suture lysis or gonio-punture were indicated and performed at the discretion of the surgeon, and they were always registered in the CRF.~Subconjunctival injections of anti-fibrotic agents and/or bleb needling were allowed and performed at the discretion of the surgeon.~DATA ANALYSIS Variables will be checked for normality using the Shapiro-Wilk test. The mean and standard deviation is going to be used to describe normally distributed variables which will be compared between independent groups using the Student t test. Variables that are found to be not normally distributed will be described by median and quartiles, and their comparison between independent groups wil be performed using the Mann-Whitney U test.

Efficacy and Safety of the ExPRESS Implant Versus Deep Sclerectomy in Combined Surgery: Prospective, Multi-center, Comparative Study

Open Angle Glaucoma, Ocular Hypertension

* Procedure: Filtration surgery with Ex-PRESS * Procedure: Non penetrating deep sclerectomy * Procedure: Cataract extraction

Inclusion Criteria:~Diagnosis of open-angle glaucoma. Points a, b and c will be required:~Glaucomatous visual field. Defined as the field presenting at least:~A group of 3 or more points with p < 5% in the pattern deviation map AND~One of them with a p < 1% in the pattern deviation map AND~Repeated in at least 2 VF.~Glaucomatous optic nerve. Defined as the optic nerve observed in color photographs presenting:~Thinning of the neuroretinal rim that can be demonstrated by an alteration in the ISNT rule.~Presence of a notch or~Presence of papillary splinter hemorrhage or~Presence of a nerve fiber layer defect or~Cup to disc (C/D) ratio asymmetry > 0.3 that cannot be explained by asymmetry in the optic disc size or~C/D ratio > 0.8 that cannot be explained by a large optic disc size~III or IV angle in Shaffer classification~Disease poorly controlled with medical treatment and/or laser at the discretion of the ophthalmologist (progression, higher than targeted pressure, poor compliance…)~Cataract with visual acuity between 0,1 (20/200) and 0.8 (20/25)~Exclusion Criteria:~Inflammatory, neovasular, closed-angle, normotensive glaucoma secondary to corticoids, or any type of glaucoma with advanced degree of functional lesion (Mean Defect < -20 dB)~Previous glaucoma surgery~Previous intraocular ocular surgery

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Intraocular pressure | mmHg | Up to 12 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Success rate at IOP <18 | percentage of patients with < of 18 mmHg in intraocular pressure | Up to 12 months | | Number of participants with adverse events assesed by questionare in case report file. | Bullet list of complications to check for at each study visit from the date of randomization upt to 12 months~List of complications in Case report file:~Avascular bleb Bleb fibrosis Choroidal effusion Corectopia Corneal edema Corneal erosion Cystoid macular edema Descemet folds Epiretinal membrane Fibrin IOL Foreign body sensation Hematic tyndall Hypotony > 1 month Hypotony Maculopathy Iris incarceration Iris synechiae Lamellar macular hole Posterior capsule opacity Postoperative shunt closure Postoperative uveitis Seidel (early) Shallow anterior chamber Subconjunctival hemorrhage Tenon Cist Transient hypotony VA declined > 2 Snellen lines Vitreous in anterior chamber | Up to 12 months | | Number of hypotensive medications needed | Number of drugs prescribed by investigator to keep IOP under target from the date of randomization up to 12 months | Up to 12 months |

Glaucoma, Ocular hypertension, Filtration surgery, Trabeculectomy with Ex-PRESS, Non penetrating deep sclerectomy, Phacoemulsification, Combined surgery

Glaucoma, Glaucoma, Open-Angle, Ocular Hypertension, Hypertension, Vascular Diseases, Cardiovascular Diseases, Eye Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Filtration surgery with Express<br>Filtration surgery with Ex-PRESS + cataract extraction (Cataract surgery and IOL implantation) | Procedure: Filtration surgery with Ex-PRESS<br>* Filtration surgery with Ex-PRESS<br>Procedure: Cataract extraction<br>* Cataract surgery and IOL implantation<br>| | Active Comparator: Non penetrating surgery<br>- Filtration surgery with Non penetrating deep sclerectomy + cataract extraction (Cataract surgery and IOL implantation) | Procedure: Non penetrating deep sclerectomy<br>* Non penetrating deep sclerectomy<br>Procedure: Cataract extraction<br>* Cataract surgery and IOL implantation<br>|

Efficacy and Safety of the ExPRESS Implant Versus Deep Sclerectomy in Combined Surgery Study Overview ================= Brief Summary ----------------- The Ex-PRESS Glaucoma Filtration Device is a small, non-valved implant that was designed to lower intraocular pressure (IOP) by shunting aqueous humor from the anterior chamber into the subconjunctival space. The implant was developed in response to the need for more straightforward, standardized and safe surgical technique than standard filtration surgery. No iridectomy and no sclerectomy is needed if an Ex-PRESS device is implanted under a partial-thickness scleral flap. This may reduce surgical time and complications when compared to a standard trabeculectomy. In some studies it has been found to be safe and effective with few complications, even in high-risk patients. No previous studies have compared filtration surgery with Ex-Press implant to deep sclerectomy. Detailed Description ----------------- Hypothesis: In combined procedure (cataract and filtering surgery), the effect of Ex-PRESS device has similar efficacy reducing intraocular pressure than non penetrant deep sclerectomy and with good level of safety. Objective: To evaluate and compare the efficacy and safety at 12 months of the filtering surgery with the Ex-PRESS device with that of deep sclerectomy. Methods: Design: Multi-center, prospective, simple-blind, randomized study. Primary variable: 1. Intraocular pressure. Secondary variables: Success rate at IOP <18 Frequency and type of complications Number of hypotensive drugs needed. Sample size calculation: Accepting an alfa risk of 0.05 and a beta risk of 0.20 in a two-sided Student's T-test, 50 subjects are necessary in first group and 50 in the second to recognize as statistically significant a difference greater than or equal to 10% in IOP, with a common standard deviation of 17%. A drop-out rate of 8% has been anticipated. If no drop-out rate is considered, the number of needed subjects is 92 (46 per group). If the drop out rate is more than 8%: If the recruitment period is open, another subjects will be included. If the recruitment period os close, the inclusion of another subject will be evaluated to maintain the statistic power of the study. Method -Single blinded. Each patient will be assigned to one of the two arms (Ex-PRESS or Deep sclerectomy) the same day of surgery. The surgeon will be informed of the randomization result just before surgery by the study coordinator. Pre-operative examinations: History summarizing previous surgical procedures, intraocular pressure while on treatment, target pressure at the discretion of the surgeon, visual field (SITA standard 24-2), gonioscopy, and a detailed description of the optic disc / nerve fiber layer by a glaucoma specialist was performed in all subjects included. Post-operative examinations Visits were undertaken at 1 day, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, and 12 months. Tests: visual fields (month 12) gonioscopy (month 12) intraocular pressure (all visits) optic disc examination (all visits, under dilation at 3 and 12 month) Pachymetry (preop exam) endothelial cell count (months 3 and 12) Bleb morphology (month 1 and 12) methodic registration of complications (all visits) A specific CRF was designed with all variables and data required for the study which included a long list of individual potential complications Pre-operative treatment. Prostaglandin analogues will be discontinued one week before surgery, but the rest of hypotensive drugs will be maintained until the day of surgery Surgery. Each patient was assigned to one of the two arms (Ex-PRESS or Deep sclerectomy) the same day of surgery. The surgeon wil be informed of the randomization result just before surgery by the study coordinator. The surgical technique is as follows: retro/peribulbar o subtenon's anesthesia, superior rectus or corneal traction suture, phacoemulsification through 2.1 to 2.8 mm incision with IOL implantation, a fornix-based conjunctival flap, sufficient but not excessive cauterization, application MMC 0,2 mg/ml for 2 minutes under the conjunctiva, then MMC was washed out with 50 ml of saline solution, then and according to the randomization result a scleral flap (5x5 mm in the NPDS, 4x4 mm in the Ex-Press group) is dissected. Group 1. Then the Ex-PRESS device was placed according to the manufacturer's instructions and its position in the anterior chamber was verified by the surgeon. Group 2. Deep sclerectomy (NPDS) was performed by dissecting a Deep scleral flap (4x4 mm) and peeling the trabeculo-descement membrane. A Esnoper (AJL, Vitoria, Spain) device was positioned under the external scleral flap and fixated with a 10/0 nylon suture. Suture Nylon 10/00 suture was used to place four or five stitches in the Ex-Press group and 2 stitches in the NPDS group. Then a hermetic conjunctival suture was performed at the limbus with 10/0 nylon. Post-operative treatment. All patients instilled Moxifloxacin Antibiotic every 6 hours for 1 week, Dexamethasone (every 2 hours for 1 month, every 4-6 hours on the second month and gradually tapered on the third month according to surgeon's instructions). Atropine was also used at the discretion of the surgeon when clinical finds recommended its use. Suture lysis or gonio-punture were indicated and performed at the discretion of the surgeon, and they were always registered in the CRF. Subconjunctival injections of anti-fibrotic agents and/or bleb needling were allowed and performed at the discretion of the surgeon. DATA ANALYSIS Variables will be checked for normality using the Shapiro-Wilk test. The mean and standard deviation is going to be used to describe normally distributed variables which will be compared between independent groups using the Student t test. Variables that are found to be not normally distributed will be described by median and quartiles, and their comparison between independent groups wil be performed using the Mann-Whitney U test. Official Title ----------------- Efficacy and Safety of the ExPRESS Implant Versus Deep Sclerectomy in Combined Surgery: Prospective, Multi-center, Comparative Study Conditions ----------------- Open Angle Glaucoma, Ocular Hypertension Intervention / Treatment ----------------- * Procedure: Filtration surgery with Ex-PRESS * Procedure: Non penetrating deep sclerectomy * Procedure: Cataract extraction Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Diagnosis of open-angle glaucoma. Points a, b and c will be required: Glaucomatous visual field. Defined as the field presenting at least: A group of 3 or more points with p < 5% in the pattern deviation map AND One of them with a p < 1% in the pattern deviation map AND Repeated in at least 2 VF. Glaucomatous optic nerve. Defined as the optic nerve observed in color photographs presenting: Thinning of the neuroretinal rim that can be demonstrated by an alteration in the ISNT rule. Presence of a notch or Presence of papillary splinter hemorrhage or Presence of a nerve fiber layer defect or Cup to disc (C/D) ratio asymmetry > 0.3 that cannot be explained by asymmetry in the optic disc size or C/D ratio > 0.8 that cannot be explained by a large optic disc size III or IV angle in Shaffer classification Disease poorly controlled with medical treatment and/or laser at the discretion of the ophthalmologist (progression, higher than targeted pressure, poor compliance…) Cataract with visual acuity between 0,1 (20/200) and 0.8 (20/25) Exclusion Criteria: Inflammatory, neovasular, closed-angle, normotensive glaucoma secondary to corticoids, or any type of glaucoma with advanced degree of functional lesion (Mean Defect < -20 dB) Previous glaucoma surgery Previous intraocular ocular surgery Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Filtration surgery with Express<br>Filtration surgery with Ex-PRESS + cataract extraction (Cataract surgery and IOL implantation) | Procedure: Filtration surgery with Ex-PRESS<br>* Filtration surgery with Ex-PRESS<br>Procedure: Cataract extraction<br>* Cataract surgery and IOL implantation<br>| | Active Comparator: Non penetrating surgery<br>- Filtration surgery with Non penetrating deep sclerectomy + cataract extraction (Cataract surgery and IOL implantation) | Procedure: Non penetrating deep sclerectomy<br>* Non penetrating deep sclerectomy<br>Procedure: Cataract extraction<br>* Cataract surgery and IOL implantation<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Intraocular pressure | mmHg | Up to 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Success rate at IOP <18 | percentage of patients with < of 18 mmHg in intraocular pressure | Up to 12 months | | Number of participants with adverse events assesed by questionare in case report file. | Bullet list of complications to check for at each study visit from the date of randomization upt to 12 months List of complications in Case report file: Avascular bleb Bleb fibrosis Choroidal effusion Corectopia Corneal edema Corneal erosion Cystoid macular edema Descemet folds Epiretinal membrane Fibrin IOL Foreign body sensation Hematic tyndall Hypotony > 1 month Hypotony Maculopathy Iris incarceration Iris synechiae Lamellar macular hole Posterior capsule opacity Postoperative shunt closure Postoperative uveitis Seidel (early) Shallow anterior chamber Subconjunctival hemorrhage Tenon Cist Transient hypotony VA declined > 2 Snellen lines Vitreous in anterior chamber | Up to 12 months | | Number of hypotensive medications needed | Number of drugs prescribed by investigator to keep IOP under target from the date of randomization up to 12 months | Up to 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Glaucoma, Ocular hypertension, Filtration surgery, Trabeculectomy with Ex-PRESS, Non penetrating deep sclerectomy, Phacoemulsification, Combined surgery

NCT05597397

Effect of Repeated Low-Level Red-Light Therapy on Retinal Function and Structure

The purpose of this clinical trial is to evaluate the effect of repeated low-level red-light (RLRL) therapy on the retinal function and structure among myopic teenagers.

Myopia constitutes a major threat to personal health globally for its increased prevalence. Moreover, its dose-related association with irreversible blindness complications such as myopic macular degeneration has been demonstrated. It is crucial to look for effective ways to control myopia in children to reduce risk of myopic pathologies in later life. Repeated low-level red-light (RLRL) therapy is an innovative and non-invasive therapeutic treatment for a variety of eye diseases. A previous randomized clinical trial suggested that RLRL could effectively controlled myopia progression without clinically observable side effects.~The purpose of this study is to evaluate the effect of RLRL on the retinal function and structure among myopic teenagers aged 15-16 years. The RLRL therapy will be carried out at school under supervision of the parents according to a standard protocol for the first month and then will be discontinued for 1 month. Detailed functional and structural examinations, including full field electroretinogram, multifocal electroretinogram, microperimetry, visual acuity, intraocular pressure, optical coherence tomography, optical coherence tomography angiography, cycloplegic spherical equivalent refraction, and biological parameters will be evaluated at 1 month, 2 months after enrollment.

Effect of Repeated Low-Level Red-Light Therapy on Retinal Function and Structure Among Myopic Teenagers

Myopia, Refractive Errors, Eye Diseases, Retina; Change

* Device: RLRL

Inclusion Criteria:~Age: 15-16 years at enrolment.~Myopia: cycloplegic spherical equivalent refractions (SERs) range from -1.00 to -5.00 diopters (D) and astigmatism less than -2.5 D in either eye.~Best corrected visual acuity equal to or better than 0.8 in either eye.~Normal fundus, or tessellated fundus.~Provision of consent and able to participate in all required activities of the study.~Exclusion Criteria:~Secondary myopia, such as a history of retinopathy of prematurity or neonatal problems, or syndromic myopia with a known genetic disease or connective tissue disorders, such as Stickler or Marfan syndrome.~Strabismus and binocular vision abnormalities in either eye.~Refractive media opacity: corneal opacities, cataract, or implanted intraocular lens, etc.~Ocular abnormalities that affect retinal function: macular degeneration, diabetic retinopathy, retinal detachment, glaucoma, or ocular hypertension, endophthalmitis, uveitis, optic neuropathy, etc.~Previous history of refractive surgery, intraocular surgery, laser therapy, and intravitreal injection, etc.~Systemic abnormalities: diabetes, hypertension, etc.~Drugs therapies with toxicity effect on the retina: hydroxychloroquine, etc.~Prior treatment of myopia control in the past three months, drugs, orthokeratology, progressive addition lenses, bifocal lens, etc.~Other contraindications, including but not limited to ocular or other systemic abnormalities, that the physician may consider inappropriate for enrolment.

15 Years

16 Years

All

Accepts Healthy Volunteers

Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in the amplitudes of waves. | Changes in the amplitudes are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by electroretinogram. | 1 and 2 months | | Changes in the latency of waves. | Changes in the latency of waves are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by electroretinogram. | 1 and 2 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in retinal sensitivity | Changes in retinal sensitivity are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by microperimetry. | 1 and 2 months | | Changes in fixation stability | Changes in fixation stability are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by microperimetry. | 1 and 2 months | | Changes in macular integrity | Changes in macular integrity are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by microperimetry. | 1 and 2 months | | Changes in macular vessel density | Changes in macular vessel density are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by optical coherence tomography angiography. | 1 and 2 months | | Changes in macular perfusion density | Changes in macular perfusion density are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by optical coherence tomography angiography. | 1 and 2 months | | Changes in chorocapillaris flow defict percentage | Changes in choroidal vascularity index are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by optical coherence tomography angiography. | 1 and 2 months | | Changes in choroidal vascularity index | Changes in choroidal vascularity index are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by optical coherence tomography. | 1 and 2 months | | Changes in best corrected visual acuity | Best corrected visual acuity changes are characterized as the difference between each follow up visit and baseline values. An Early Treatment Diabetic Retinopathy Study chart with standard illumination at a distance of 4 meters is used to measure best corrected visual acuity. | 1 and 2 months |

Eye Diseases, Refractive Errors

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Repeated Low-Level Red-Light Therapy (RLRL)<br>Single vision spectacles (SVS) & RLRL. | Device: RLRL<br>* In addition to SVS with power for correcting distance refraction, RLRL will be performed twice per school day with an interval of at least 4 hours, each treatment last 3 minutes.<br>|

Effect of Repeated Low-Level Red-Light Therapy on Retinal Function and Structure Study Overview ================= Brief Summary ----------------- The purpose of this clinical trial is to evaluate the effect of repeated low-level red-light (RLRL) therapy on the retinal function and structure among myopic teenagers. Detailed Description ----------------- Myopia constitutes a major threat to personal health globally for its increased prevalence. Moreover, its dose-related association with irreversible blindness complications such as myopic macular degeneration has been demonstrated. It is crucial to look for effective ways to control myopia in children to reduce risk of myopic pathologies in later life. Repeated low-level red-light (RLRL) therapy is an innovative and non-invasive therapeutic treatment for a variety of eye diseases. A previous randomized clinical trial suggested that RLRL could effectively controlled myopia progression without clinically observable side effects. The purpose of this study is to evaluate the effect of RLRL on the retinal function and structure among myopic teenagers aged 15-16 years. The RLRL therapy will be carried out at school under supervision of the parents according to a standard protocol for the first month and then will be discontinued for 1 month. Detailed functional and structural examinations, including full field electroretinogram, multifocal electroretinogram, microperimetry, visual acuity, intraocular pressure, optical coherence tomography, optical coherence tomography angiography, cycloplegic spherical equivalent refraction, and biological parameters will be evaluated at 1 month, 2 months after enrollment. Official Title ----------------- Effect of Repeated Low-Level Red-Light Therapy on Retinal Function and Structure Among Myopic Teenagers Conditions ----------------- Myopia, Refractive Errors, Eye Diseases, Retina; Change Intervention / Treatment ----------------- * Device: RLRL Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age: 15-16 years at enrolment. Myopia: cycloplegic spherical equivalent refractions (SERs) range from -1.00 to -5.00 diopters (D) and astigmatism less than -2.5 D in either eye. Best corrected visual acuity equal to or better than 0.8 in either eye. Normal fundus, or tessellated fundus. Provision of consent and able to participate in all required activities of the study. Exclusion Criteria: Secondary myopia, such as a history of retinopathy of prematurity or neonatal problems, or syndromic myopia with a known genetic disease or connective tissue disorders, such as Stickler or Marfan syndrome. Strabismus and binocular vision abnormalities in either eye. Refractive media opacity: corneal opacities, cataract, or implanted intraocular lens, etc. Ocular abnormalities that affect retinal function: macular degeneration, diabetic retinopathy, retinal detachment, glaucoma, or ocular hypertension, endophthalmitis, uveitis, optic neuropathy, etc. Previous history of refractive surgery, intraocular surgery, laser therapy, and intravitreal injection, etc. Systemic abnormalities: diabetes, hypertension, etc. Drugs therapies with toxicity effect on the retina: hydroxychloroquine, etc. Prior treatment of myopia control in the past three months, drugs, orthokeratology, progressive addition lenses, bifocal lens, etc. Other contraindications, including but not limited to ocular or other systemic abnormalities, that the physician may consider inappropriate for enrolment. Ages Eligible for Study ----------------- Minimum Age: 15 Years Maximum Age: 16 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Repeated Low-Level Red-Light Therapy (RLRL)<br>Single vision spectacles (SVS) & RLRL. | Device: RLRL<br>* In addition to SVS with power for correcting distance refraction, RLRL will be performed twice per school day with an interval of at least 4 hours, each treatment last 3 minutes.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in the amplitudes of waves. | Changes in the amplitudes are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by electroretinogram. | 1 and 2 months | | Changes in the latency of waves. | Changes in the latency of waves are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by electroretinogram. | 1 and 2 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in retinal sensitivity | Changes in retinal sensitivity are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by microperimetry. | 1 and 2 months | | Changes in fixation stability | Changes in fixation stability are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by microperimetry. | 1 and 2 months | | Changes in macular integrity | Changes in macular integrity are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by microperimetry. | 1 and 2 months | | Changes in macular vessel density | Changes in macular vessel density are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by optical coherence tomography angiography. | 1 and 2 months | | Changes in macular perfusion density | Changes in macular perfusion density are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by optical coherence tomography angiography. | 1 and 2 months | | Changes in chorocapillaris flow defict percentage | Changes in choroidal vascularity index are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by optical coherence tomography angiography. | 1 and 2 months | | Changes in choroidal vascularity index | Changes in choroidal vascularity index are characterized as the difference between each follow-up visit and corresponding baseline values which are measured by optical coherence tomography. | 1 and 2 months | | Changes in best corrected visual acuity | Best corrected visual acuity changes are characterized as the difference between each follow up visit and baseline values. An Early Treatment Diabetic Retinopathy Study chart with standard illumination at a distance of 4 meters is used to measure best corrected visual acuity. | 1 and 2 months |

NCT00457210

The Influence of Radiotherapy on Cognitive Function

The cognitive function of 150 patients that undergone any Radiotherapy treatment to the brain will be assessed at 3 time points before and after the treatment.

The basic cognitive function and QOL of 150 oncologic patients that undergone Radiotherapy or Radiosurgery treatment to the brain due to primary tumor, metastases or increased risk of brain metastases, will be assessed at 3 time points: before the treatment, immediately after the treatment, and on the next follow up visit. The assessment tools that will be used are Neurotrax standard cognitive computerized tests and 2 short questionnaires.Patients that will receive a one-day treatment will be tested on 2 time points only- before the treatment and on FU.The research will reveal the positive and the negative influences of the Radiotherapy, along with the assessment of norms for the cognitive function and quality of life of oncologic patients being treated by RT.Eligibility criteria:oncologic patients of both genders, with primary brain tumors, metastases or with increased risk of brain metastases, that are referred to conformal/palliative or preventive Radiotherapy treatment or to Stereotactic Radiosurgery, who are able to follow instructions in Hebrew.The participants will be 20-80 years old.Main comparisons will be performed between the cognitive tests results on 3 time points mentioned. The study will continue until the needed number of participants will be achieved.

The Influence of the Radiotherapy or Stereotactic Radiosurgery on the Cognitive Function of the Patients With the Neurotrax Assessment System and a Cognitive Questionnaire.

Radiotherapy, Brain Neoplasms, Quality of Life

* Procedure: Brain Radiotherapy/Stereotactic Radiosurgery

Inclusion Criteria:~20-80 years old oncologic patients, of both genders, that are referred to Brain Radiotherapy or Stereotactic Radiosurgery due to primary brain tumor/ brain metastases or increased risk for brain metastases.~Are able to follow instructions in Hebrew.~Exclusion Criteria:~Non-Hebrew speakers can not participate.

20 Years

80 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- |

Psychology

Brain Neoplasms, Central Nervous System Neoplasms, Nervous System Neoplasms, Neoplasms by Site, Neoplasms, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases

| Intervention/Treatment | | --- | |Procedure: Brain Radiotherapy/Stereotactic Radiosurgery|nan|

The Influence of Radiotherapy on Cognitive Function Study Overview ================= Brief Summary ----------------- The cognitive function of 150 patients that undergone any Radiotherapy treatment to the brain will be assessed at 3 time points before and after the treatment. Detailed Description ----------------- The basic cognitive function and QOL of 150 oncologic patients that undergone Radiotherapy or Radiosurgery treatment to the brain due to primary tumor, metastases or increased risk of brain metastases, will be assessed at 3 time points: before the treatment, immediately after the treatment, and on the next follow up visit. The assessment tools that will be used are Neurotrax standard cognitive computerized tests and 2 short questionnaires.Patients that will receive a one-day treatment will be tested on 2 time points only- before the treatment and on FU.The research will reveal the positive and the negative influences of the Radiotherapy, along with the assessment of norms for the cognitive function and quality of life of oncologic patients being treated by RT.Eligibility criteria:oncologic patients of both genders, with primary brain tumors, metastases or with increased risk of brain metastases, that are referred to conformal/palliative or preventive Radiotherapy treatment or to Stereotactic Radiosurgery, who are able to follow instructions in Hebrew.The participants will be 20-80 years old.Main comparisons will be performed between the cognitive tests results on 3 time points mentioned. The study will continue until the needed number of participants will be achieved. Official Title ----------------- The Influence of the Radiotherapy or Stereotactic Radiosurgery on the Cognitive Function of the Patients With the Neurotrax Assessment System and a Cognitive Questionnaire. Conditions ----------------- Radiotherapy, Brain Neoplasms, Quality of Life Intervention / Treatment ----------------- * Procedure: Brain Radiotherapy/Stereotactic Radiosurgery Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 20-80 years old oncologic patients, of both genders, that are referred to Brain Radiotherapy or Stereotactic Radiosurgery due to primary brain tumor/ brain metastases or increased risk for brain metastases. Are able to follow instructions in Hebrew. Exclusion Criteria: Non-Hebrew speakers can not participate. Ages Eligible for Study ----------------- Minimum Age: 20 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Intervention/Treatment | | --- | |Procedure: Brain Radiotherapy/Stereotactic Radiosurgery|nan| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Psychology

NCT00789503

Nursing-Home Residents Given Bread Fortified With Vitamin D3

Background. For older adults, serum 25-hydroxyvitamin D (25(OH)D) higher than 75 nmol/L lowers fracture risk and attainment of this 25(OH)D target may require 125 mcg (5000 IU)/d of vitamin D3.~Objective: We wanted to characterize the safety and efficacy of fortifying bread with a biologically meaningful amount of vitamin D3.

Methods: In a single-arm design, 45 nursing-home residents consumed one bun/d that had been fortified with 125 mcg (5,000 IU) of vitamin D3 and 320 mg elemental calcium.

Long-Term Effects of Giving Nursing-Home Residents Bread Fortified With 125 Micrograms (5000 IU) Vitamin D3 Per Daily Serving

Vitamin D Deficiency, Low Bone Density

* Dietary Supplement: Bread fortified with vitamin D3 and calcium

Inclusion Criteria:~Healthy seniors in an institution in Romania~Exclusion Criteria:~Known hypercalcemic or hypercalciuric disease

58 Years

89 Years

All

Accepts Healthy Volunteers

Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Serum 25-hydroxyvitamin D response | | 12 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Effects on serum calcium | | 12 months | | Effects on urine calcium | | 12 months | | Change in spine and hip bone mineral density, baseline vs final | | 12 months | | Change in parathyroid hormone, baseline vs final | | 12 months |

dietary fortification, Vitamin D3, Osteomalacia, bread, bone mineral density, geriatrics, cholecalciferol, calcidiol, osteoporosis, dual-energy photon absorptiometry, bread fortification

Vitamin D, Cholecalciferol, Calcium, Vitamins, Micronutrients, Physiological Effects of Drugs, Calcium-Regulating Hormones and Agents, Bone Density Conservation Agents

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Bread fortified with vitamin D3 and calcium<br> | Dietary Supplement: Bread fortified with vitamin D3 and calcium<br>* Bread fortified with vitamin D3 (5000 IU per bun) and calcium<br>|

Nursing-Home Residents Given Bread Fortified With Vitamin D3 Study Overview ================= Brief Summary ----------------- Background. For older adults, serum 25-hydroxyvitamin D (25(OH)D) higher than 75 nmol/L lowers fracture risk and attainment of this 25(OH)D target may require 125 mcg (5000 IU)/d of vitamin D3. Objective: We wanted to characterize the safety and efficacy of fortifying bread with a biologically meaningful amount of vitamin D3. Detailed Description ----------------- Methods: In a single-arm design, 45 nursing-home residents consumed one bun/d that had been fortified with 125 mcg (5,000 IU) of vitamin D3 and 320 mg elemental calcium. Official Title ----------------- Long-Term Effects of Giving Nursing-Home Residents Bread Fortified With 125 Micrograms (5000 IU) Vitamin D3 Per Daily Serving Conditions ----------------- Vitamin D Deficiency, Low Bone Density Intervention / Treatment ----------------- * Dietary Supplement: Bread fortified with vitamin D3 and calcium Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Healthy seniors in an institution in Romania Exclusion Criteria: Known hypercalcemic or hypercalciuric disease Ages Eligible for Study ----------------- Minimum Age: 58 Years Maximum Age: 89 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Bread fortified with vitamin D3 and calcium<br> | Dietary Supplement: Bread fortified with vitamin D3 and calcium<br>* Bread fortified with vitamin D3 (5000 IU per bun) and calcium<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Serum 25-hydroxyvitamin D response | | 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Effects on serum calcium | | 12 months | | Effects on urine calcium | | 12 months | | Change in spine and hip bone mineral density, baseline vs final | | 12 months | | Change in parathyroid hormone, baseline vs final | | 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- dietary fortification, Vitamin D3, Osteomalacia, bread, bone mineral density, geriatrics, cholecalciferol, calcidiol, osteoporosis, dual-energy photon absorptiometry, bread fortification

NCT00549172

Arthroscopy in the Treatment of Degenerative Medial Meniscus Tear

Degenerative meniscal tears are the most common etiology for knee pain, swelling and loss of function. Partial arthroscopic meniscectomy is the most common orthopaedic procedure to treat meniscal tears. Improvements have been reported both after arthroscopy and with conservative treatment, however no direct comparison exist. Accordingly, the aim of this study is to assess the efficacy of arthroscopic partial meniscectomy for the treatment of degenerative tear of medial meniscus of the knee using a double-blind, placebo controlled, randomised trial.

Middle-aged men and women with degenerative meniscal tears constitute a large group of patients presenting with knee pain, sometimes accompanied with swelling and loss of function. Many meniscal tears occur without a trauma in physically active individuals as well as in older people and could be a part of early osteoarthritis. Partial arthroscopic meniscectomy is the most common orthopaedic procedure and is used to treat patients with meniscal tears. Many patients report improvement after arthroscopy referring especially to reduced knee pain, better knee function and improved quality of life. However, similar results have also been obtained with conservative treatment (physical therapy) of patients with degenerative meniscal tears. Accordingly, the aim of this study is to assess the efficacy of arthroscopic partial meniscectomy for the treatment of degenerative tear of medial meniscus of the knee using a double-blind, placebo controlled, randomised trial. The outcome of arthroscopic partial meniscectomy (vs. sham surgery) is assessed using the Lysholm knee score and pain at rest and activity (VAS) at 2, 6 and 12 months after the operation. In addition, the functional outcome is assessed using the WOMET knee score (a disease-specific quality of life -knee score development on the assessment of meniscal pathology), the general quality of life score (15-D), and cost-effectiveness analysis.

Efficacy of Arthroscopic Partial Resection for the Degenerative Tear of the Medial Meniscus of a Knee

Osteoarthritis, Knee

* Procedure: Operative (partial arthroscopy) * Procedure: Conservative (diagnostic arthroscopy)

Inclusion Criteria:~Age: 35 to 65 years of age.~A pain located on the medial joint line of the knee that has persistent at least for 3 months.~Pain that can be provoked by palpation or compression of the joint line or a positive McMurray sign.~Tear of the medial meniscus on MRI.~Degenerative rupture of the medial meniscus confirmed at arthroscopy.~Exclusion Criteria:~Acute, trauma-induced onset of symptoms.~Locking or painful snapping of the knee joint.~A surgical operation performed on the affected knee.~Osteoarthritis of the medial compartment of the knee (determined by clinical criteria of the ACR).~Osteoarthritis on knee radiographs (Kellgren-Lawrence > 1).~Acute (within the previous year) fractures of the knee.~Decreased range of motion of the knee.~Instability of the knee.~MRI assessment showing a tumor or any other complaint requiring surgical or other means of treatment.~Arthroscopic assessment showing anything other than a degenerative tear of the medial meniscus requiring surgical intervention.

35 Years

65 Years

All

Accepts Healthy Volunteers

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The Lysholm Knee Score | The Lysholm knee score is based on an eight-item questionnaire designed to evaluate knee function and symptoms in activities of daily living. Scores range from 0 to 100; higher scores indicate less severe symptoms. | One year | | Pain After Exercise (VAS) | Knee pain after exercise (during the preceding week) was assessed on a rating scale of 0 to 10, with 0 denoting no pain and 10 denoting extreme pain. | One year | | WOMET (Western Ontario Meniscal Tear -Disease Specific Quality of Life -Assessment Tool) | The Western Ontario Meniscal Evaluation Tool (WOMET) contains 16 items addressing three domains: 9 items addressing physical symptoms; 4 items addressing disabilities with regard to sports, recreation, work, and lifestyle; and 3 items addressing emotions. The score indicates the percentage of a normal score; therefore, 100 is the best possible score, and 0 is the worst possible score. | One year |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | 15-D (General Quality of Life -Assessment Tool) | The 15D instrument is a generic health-related quality-of-life instrument comprising 15 dimensions. The maximum 15D score is 1 (full health), and the minimum score is 0 (death). | One year | | Pain at Rest (VAS) | Knee pain at rest (during the preceding week) was assessed on a rating scale of 0 to 10, with 0 denoting no pain and 10 denoting extreme pain. | One year | | Cost Effectiveness | Cost effectiveness data comparing arthroscopic partial meniscectomy and diagnostic arthroscopy. Costs are based on healthcare utilisation and sickness absence. | 1 and 2 years |

Osteoarthritis, Knee, Arthroscopic Surgery, Menisci, Medial, Placebo Effect, Treatment Efficacy

Osteoarthritis, Osteoarthritis, Knee, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Operative (O)<br>Partial resection of degenerative tear of medial meniscus | Procedure: Operative (partial arthroscopy)<br>* Partial arthroscopic resection of degenerative rupture of the medial meniscus<br>| | Sham Comparator: Conservative (K)<br>Arthroscopy (diagnostic) | Procedure: Conservative (diagnostic arthroscopy)<br>* Diagnostic arthroscopy<br>|

Arthroscopy in the Treatment of Degenerative Medial Meniscus Tear Study Overview ================= Brief Summary ----------------- Degenerative meniscal tears are the most common etiology for knee pain, swelling and loss of function. Partial arthroscopic meniscectomy is the most common orthopaedic procedure to treat meniscal tears. Improvements have been reported both after arthroscopy and with conservative treatment, however no direct comparison exist. Accordingly, the aim of this study is to assess the efficacy of arthroscopic partial meniscectomy for the treatment of degenerative tear of medial meniscus of the knee using a double-blind, placebo controlled, randomised trial. Detailed Description ----------------- Middle-aged men and women with degenerative meniscal tears constitute a large group of patients presenting with knee pain, sometimes accompanied with swelling and loss of function. Many meniscal tears occur without a trauma in physically active individuals as well as in older people and could be a part of early osteoarthritis. Partial arthroscopic meniscectomy is the most common orthopaedic procedure and is used to treat patients with meniscal tears. Many patients report improvement after arthroscopy referring especially to reduced knee pain, better knee function and improved quality of life. However, similar results have also been obtained with conservative treatment (physical therapy) of patients with degenerative meniscal tears. Accordingly, the aim of this study is to assess the efficacy of arthroscopic partial meniscectomy for the treatment of degenerative tear of medial meniscus of the knee using a double-blind, placebo controlled, randomised trial. The outcome of arthroscopic partial meniscectomy (vs. sham surgery) is assessed using the Lysholm knee score and pain at rest and activity (VAS) at 2, 6 and 12 months after the operation. In addition, the functional outcome is assessed using the WOMET knee score (a disease-specific quality of life -knee score development on the assessment of meniscal pathology), the general quality of life score (15-D), and cost-effectiveness analysis. Official Title ----------------- Efficacy of Arthroscopic Partial Resection for the Degenerative Tear of the Medial Meniscus of a Knee Conditions ----------------- Osteoarthritis, Knee Intervention / Treatment ----------------- * Procedure: Operative (partial arthroscopy) * Procedure: Conservative (diagnostic arthroscopy) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age: 35 to 65 years of age. A pain located on the medial joint line of the knee that has persistent at least for 3 months. Pain that can be provoked by palpation or compression of the joint line or a positive McMurray sign. Tear of the medial meniscus on MRI. Degenerative rupture of the medial meniscus confirmed at arthroscopy. Exclusion Criteria: Acute, trauma-induced onset of symptoms. Locking or painful snapping of the knee joint. A surgical operation performed on the affected knee. Osteoarthritis of the medial compartment of the knee (determined by clinical criteria of the ACR). Osteoarthritis on knee radiographs (Kellgren-Lawrence > 1). Acute (within the previous year) fractures of the knee. Decreased range of motion of the knee. Instability of the knee. MRI assessment showing a tumor or any other complaint requiring surgical or other means of treatment. Arthroscopic assessment showing anything other than a degenerative tear of the medial meniscus requiring surgical intervention. Ages Eligible for Study ----------------- Minimum Age: 35 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Operative (O)<br>Partial resection of degenerative tear of medial meniscus | Procedure: Operative (partial arthroscopy)<br>* Partial arthroscopic resection of degenerative rupture of the medial meniscus<br>| | Sham Comparator: Conservative (K)<br>Arthroscopy (diagnostic) | Procedure: Conservative (diagnostic arthroscopy)<br>* Diagnostic arthroscopy<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The Lysholm Knee Score | The Lysholm knee score is based on an eight-item questionnaire designed to evaluate knee function and symptoms in activities of daily living. Scores range from 0 to 100; higher scores indicate less severe symptoms. | One year | | Pain After Exercise (VAS) | Knee pain after exercise (during the preceding week) was assessed on a rating scale of 0 to 10, with 0 denoting no pain and 10 denoting extreme pain. | One year | | WOMET (Western Ontario Meniscal Tear -Disease Specific Quality of Life -Assessment Tool) | The Western Ontario Meniscal Evaluation Tool (WOMET) contains 16 items addressing three domains: 9 items addressing physical symptoms; 4 items addressing disabilities with regard to sports, recreation, work, and lifestyle; and 3 items addressing emotions. The score indicates the percentage of a normal score; therefore, 100 is the best possible score, and 0 is the worst possible score. | One year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | 15-D (General Quality of Life -Assessment Tool) | The 15D instrument is a generic health-related quality-of-life instrument comprising 15 dimensions. The maximum 15D score is 1 (full health), and the minimum score is 0 (death). | One year | | Pain at Rest (VAS) | Knee pain at rest (during the preceding week) was assessed on a rating scale of 0 to 10, with 0 denoting no pain and 10 denoting extreme pain. | One year | | Cost Effectiveness | Cost effectiveness data comparing arthroscopic partial meniscectomy and diagnostic arthroscopy. Costs are based on healthcare utilisation and sickness absence. | 1 and 2 years | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Osteoarthritis, Knee, Arthroscopic Surgery, Menisci, Medial, Placebo Effect, Treatment Efficacy

NCT03489876

Synthetic Cartilage Implant vs Osteochondral Autograft Transfer for Advanced 1st Metatarsal Phalangeal Joint Arthritis

This is a prospective, randomized, controlled clinical trial comparing synthetic cartilage implantation versus osteochondral autograft transfer for treatment of first metatarsophalangeal (MTP) arthritis. This data will allow for accurate comparisons between the two groups in regards to functional outcome, clinical outcome, pain relief, and complications.

First MTP joint arthritis or hallux rigidus is the most common arthritic condition of the foot. Historically, there have been several options to treat this condition surgically, but the current standard for advanced hallux rigidus is first MTP anthrodesis. Newer joint preserving procedures offer patients effective relief of pain and improving functional outcomes as well as maintaining, and potentially improving, range of motion for the first MTP joint. Osteochondral autograft transfer has been shown to be an effective treatment for hallux rigidus, and involves harvesting a small cylindrical osteochondral graft from a site remote of the first MTP joint and transferring the graft to the head of the first metatarsal. A new synthetic cartilage implant, Cartiva, has been shown to have equivalent functional outcomes, pain scores, and complications to anthrodesis, but the first MTP range of motion in the Cartiva group was maintained or even improved in some patients.~This is a prospective, randomized, controlled clinical trial comparing synthetic cartilage implantation versus osteochondral autograft transfer for treatment of first metatarsophalangeal (MTP) arthritis. The hypothesis is that clinical range of motion, pain scores, subjective clinical outcomes, and complications will not be clinically inferior with the synthetic cartilage implant group compared to the osteochondral autograft transfer group.

Comparison of Synthetic Cartilage Implant Versus Osteochondral Autologous Transfer for Advanced Hallux Rigidus, A Prospective Randomized Controlled Clinical Trial

Metatarsophalangeal Joint Arthritis

* Device: Synthetic Cartilage Implant * Procedure: Osteochondral Autograft Transfer

Inclusion Criteria:~Between the ages of 18 and 80 years old~Grade 2 or 3 hallux rigidus based on Coughlin and Shurnas classification~Presence of good bone stock as determined on pre-operative x-rays not requiring bone grafting~Capable of consenting for self~Exclusion Criteria:~Patients <18 years of age~Grade 1 or 4 hallux rigidus based on Coughlin and Shurnas classification~Active bacterial infection of the foot~Previous bilateral total knee arthroplasty~Previous fracture or significant trauma to the ipsilateral knee~Inflammatory anthropathy~Gout~Inadequate bone stock~Previous anthrodesis or arthroplasty performed on the ipsilateral first MTP

18 Years

80 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Upon eligibility verification and informed consent, computer-based randomization will allot patients into one of the two treatment groups, either synthetic cartilage implant or osteochondral autograft transfer. Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Range of Motion | Pre-operative and post-operative clinical range of motion of the first MTP joint | 2 years | | Patient's Pain Level | Pre-operative and post-operative visual analog pain scale | 2 years |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Patient's Quality of Life | Foot and Ankle Ability Measure (FAAM) sports score uses patient-report to determine function | 2 years | | Clinically-Assessed Foot and Ankle Function | American Orthopedic Foot and Ankle Score (AOFAS) Hallux Metatarsophalangeal-Interphalangeal Scale | 2 years | | Health Status | 12-item short form health survey, use of concomitant medications, and changes in health status | 2 years | | Surgical Complications | Fractures, nerve injuries, blood loss, infection, etc. | 2 years | | Implant Failure | Failure of the Cartiva Synthetic Cartilage Implant | 2 years | | Secondary Surgical Intervention | Additional subsequent procedures, including removal, reoperation, revision, or supplemental fixation | 2 years |

Metatarsophalangeal Joint, Arthritis, Synthetic Cartilage Implant, Cartiva, Osteochondral Autograft Transfer

Arthritis, Joint Diseases, Musculoskeletal Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Synthetic Cartilage Implant<br>Participants receive the synthetic cartilage implant. The synthetic cartilage implant that will be used is the Cartiva implant. | Device: Synthetic Cartilage Implant<br>* The Synthetic Cartilage Implant will be implanted in to the first metatarsal head according to the manufacturer's recommendations.<br>* Other names: Cartiva;| | Active Comparator: Osteochondral Autograft Transfer<br>Participants receive the current standard osteochondral autograft transfer procedure. | Procedure: Osteochondral Autograft Transfer<br>* The osteochondral autograft transfer will be harvested from the ipsilateral lateral femoral condyle (or contralateral if a previous ipsilateral total knee anthroplasty or trauma) and the graft will be transferred to the first metatarsal head.<br>|

Synthetic Cartilage Implant vs Osteochondral Autograft Transfer for Advanced 1st Metatarsal Phalangeal Joint Arthritis Study Overview ================= Brief Summary ----------------- This is a prospective, randomized, controlled clinical trial comparing synthetic cartilage implantation versus osteochondral autograft transfer for treatment of first metatarsophalangeal (MTP) arthritis. This data will allow for accurate comparisons between the two groups in regards to functional outcome, clinical outcome, pain relief, and complications. Detailed Description ----------------- First MTP joint arthritis or hallux rigidus is the most common arthritic condition of the foot. Historically, there have been several options to treat this condition surgically, but the current standard for advanced hallux rigidus is first MTP anthrodesis. Newer joint preserving procedures offer patients effective relief of pain and improving functional outcomes as well as maintaining, and potentially improving, range of motion for the first MTP joint. Osteochondral autograft transfer has been shown to be an effective treatment for hallux rigidus, and involves harvesting a small cylindrical osteochondral graft from a site remote of the first MTP joint and transferring the graft to the head of the first metatarsal. A new synthetic cartilage implant, Cartiva, has been shown to have equivalent functional outcomes, pain scores, and complications to anthrodesis, but the first MTP range of motion in the Cartiva group was maintained or even improved in some patients. This is a prospective, randomized, controlled clinical trial comparing synthetic cartilage implantation versus osteochondral autograft transfer for treatment of first metatarsophalangeal (MTP) arthritis. The hypothesis is that clinical range of motion, pain scores, subjective clinical outcomes, and complications will not be clinically inferior with the synthetic cartilage implant group compared to the osteochondral autograft transfer group. Official Title ----------------- Comparison of Synthetic Cartilage Implant Versus Osteochondral Autologous Transfer for Advanced Hallux Rigidus, A Prospective Randomized Controlled Clinical Trial Conditions ----------------- Metatarsophalangeal Joint Arthritis Intervention / Treatment ----------------- * Device: Synthetic Cartilage Implant * Procedure: Osteochondral Autograft Transfer Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Between the ages of 18 and 80 years old Grade 2 or 3 hallux rigidus based on Coughlin and Shurnas classification Presence of good bone stock as determined on pre-operative x-rays not requiring bone grafting Capable of consenting for self Exclusion Criteria: Patients <18 years of age Grade 1 or 4 hallux rigidus based on Coughlin and Shurnas classification Active bacterial infection of the foot Previous bilateral total knee arthroplasty Previous fracture or significant trauma to the ipsilateral knee Inflammatory anthropathy Gout Inadequate bone stock Previous anthrodesis or arthroplasty performed on the ipsilateral first MTP Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Upon eligibility verification and informed consent, computer-based randomization will allot patients into one of the two treatment groups, either synthetic cartilage implant or osteochondral autograft transfer. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Synthetic Cartilage Implant<br>Participants receive the synthetic cartilage implant. The synthetic cartilage implant that will be used is the Cartiva implant. | Device: Synthetic Cartilage Implant<br>* The Synthetic Cartilage Implant will be implanted in to the first metatarsal head according to the manufacturer's recommendations.<br>* Other names: Cartiva;| | Active Comparator: Osteochondral Autograft Transfer<br>Participants receive the current standard osteochondral autograft transfer procedure. | Procedure: Osteochondral Autograft Transfer<br>* The osteochondral autograft transfer will be harvested from the ipsilateral lateral femoral condyle (or contralateral if a previous ipsilateral total knee anthroplasty or trauma) and the graft will be transferred to the first metatarsal head.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Range of Motion | Pre-operative and post-operative clinical range of motion of the first MTP joint | 2 years | | Patient's Pain Level | Pre-operative and post-operative visual analog pain scale | 2 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Patient's Quality of Life | Foot and Ankle Ability Measure (FAAM) sports score uses patient-report to determine function | 2 years | | Clinically-Assessed Foot and Ankle Function | American Orthopedic Foot and Ankle Score (AOFAS) Hallux Metatarsophalangeal-Interphalangeal Scale | 2 years | | Health Status | 12-item short form health survey, use of concomitant medications, and changes in health status | 2 years | | Surgical Complications | Fractures, nerve injuries, blood loss, infection, etc. | 2 years | | Implant Failure | Failure of the Cartiva Synthetic Cartilage Implant | 2 years | | Secondary Surgical Intervention | Additional subsequent procedures, including removal, reoperation, revision, or supplemental fixation | 2 years | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Metatarsophalangeal Joint, Arthritis, Synthetic Cartilage Implant, Cartiva, Osteochondral Autograft Transfer

NCT05326555

Dynamic Vision Testing and Concussion Management Dream Team 65

The purpose of this study is to determine the value of including dynamic vision testing into California State University, Northridge (CSUN) Athletics' established concussion protocol. The study's hypotheses are 1) dynamic vision testing will reveal vision impairments right after a person sustains a concussion, 2) these impairments may still be present upon clearance to return to play.

The subjects of interest are CSUN student-athletes who give consent to participate in the study. Dynamic vision will be assessed through the administration of the Dynamic Visual Acuity (DVA) test and the Gaze Stabilization Test (GST). Additionally, the 6-condition Balance Error Scoring System (BESS), which is currently a component of CSUN's established concussion protocol, will be administered to assess balance impairments. This cluster of tests will be administered three times per athlete: (1) during preseason to establish baseline measures, (2) acutely post-concussion once the athlete subject has been cleared by the team physician for return to exercise, and (3) when cleared to return to sport. The results will be used to evaluate whether or not dynamic vision results have returned to baseline by the time that CSUN Athletics clears the athlete to Return to Play.

Dynamic Vision Testing and Concussion Management Dream Team 65

Head Injury, Sport Injury, Concussion, Brain

* Diagnostic Test: Dynamic Vision Testing (Bertec Vision Advantage System) and Balance Error Scoring System

Inclusion Criteria:~• California State University Northridge athletes~Participants are able to give consent to participate in the study~Completion of preseason testing for the 6-condition, BESS, DVA, GST with the research team~Sustained a concussion as diagnosed by the medical staff during the 2020-2021 season of play.~Sampling of convenience on a volunteer basis~Exclusion Criteria:~• Athletes with preseason baseline tests on BESS or DVA that are not within the normative value range for an unimpaired individual.~The initial 6- condition BESS score is >20 errors~The subject is unable to attain a minimum of 85 degrees per second of horizontal head rotation when performing the DVA test.

All

Accepts Healthy Volunteers

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | 6-Condition BESS | Number of errors and time subject was able to hold position | October 1, 2021 - October 1, 2024 | | Gaze Stabilization Test (GST) | Maximum head velocity in degrees/second | October 1, 2021 - October 1, 2024 | | Dynamic Visual Acuity (DVA) | Log of minimal angle resolvable units (LogMAR). The number of lines on an eye chart that are lost with head moving (DVA) compared to the head steady condition, known as static visual acuity (SVA) | October 1, 2021 - October 1, 2024 |

Imidacloprid, Cholinergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs

| Intervention/Treatment | | --- | |Diagnostic Test: Dynamic Vision Testing (Bertec Vision Advantage System) and Balance Error Scoring System|Assessment tool and computerized tests designed to evaluate postural stability and vestibulo-ocular reflex (VOR) function while assisting with return to play decision after a sports-related concussion.|

Dynamic Vision Testing and Concussion Management Dream Team 65 Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine the value of including dynamic vision testing into California State University, Northridge (CSUN) Athletics' established concussion protocol. The study's hypotheses are 1) dynamic vision testing will reveal vision impairments right after a person sustains a concussion, 2) these impairments may still be present upon clearance to return to play. Detailed Description ----------------- The subjects of interest are CSUN student-athletes who give consent to participate in the study. Dynamic vision will be assessed through the administration of the Dynamic Visual Acuity (DVA) test and the Gaze Stabilization Test (GST). Additionally, the 6-condition Balance Error Scoring System (BESS), which is currently a component of CSUN's established concussion protocol, will be administered to assess balance impairments. This cluster of tests will be administered three times per athlete: (1) during preseason to establish baseline measures, (2) acutely post-concussion once the athlete subject has been cleared by the team physician for return to exercise, and (3) when cleared to return to sport. The results will be used to evaluate whether or not dynamic vision results have returned to baseline by the time that CSUN Athletics clears the athlete to Return to Play. Official Title ----------------- Dynamic Vision Testing and Concussion Management Dream Team 65 Conditions ----------------- Head Injury, Sport Injury, Concussion, Brain Intervention / Treatment ----------------- * Diagnostic Test: Dynamic Vision Testing (Bertec Vision Advantage System) and Balance Error Scoring System Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: • California State University Northridge athletes Participants are able to give consent to participate in the study Completion of preseason testing for the 6-condition, BESS, DVA, GST with the research team Sustained a concussion as diagnosed by the medical staff during the 2020-2021 season of play. Sampling of convenience on a volunteer basis Exclusion Criteria: • Athletes with preseason baseline tests on BESS or DVA that are not within the normative value range for an unimpaired individual. The initial 6- condition BESS score is >20 errors The subject is unable to attain a minimum of 85 degrees per second of horizontal head rotation when performing the DVA test. Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Intervention/Treatment | | --- | |Diagnostic Test: Dynamic Vision Testing (Bertec Vision Advantage System) and Balance Error Scoring System|Assessment tool and computerized tests designed to evaluate postural stability and vestibulo-ocular reflex (VOR) function while assisting with return to play decision after a sports-related concussion.| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | 6-Condition BESS | Number of errors and time subject was able to hold position | October 1, 2021 - October 1, 2024 | | Gaze Stabilization Test (GST) | Maximum head velocity in degrees/second | October 1, 2021 - October 1, 2024 | | Dynamic Visual Acuity (DVA) | Log of minimal angle resolvable units (LogMAR). The number of lines on an eye chart that are lost with head moving (DVA) compared to the head steady condition, known as static visual acuity (SVA) | October 1, 2021 - October 1, 2024 |

NCT04341896

Healthcare Utilization in Obese Caregiver Living Donors

The goal of this study is to estimate risk of post-donation healthcare use attributable to informal caregiving among obese living donors. Improving our understanding of the relationship between caregiving, donation, and healthcare use will allow us to improve living donor informed consent and post-donation care, particularly among older donors and those of minority race/ethnicity.

Caregiver burden is a well-known issue of primary caregiving for individuals with chronic disease, including transplant candidates and recipients. Informal caregiving is associated with an estimated $306 billion in unpaid labor costs and an average of $7,000 in out-of-pocket expenses related to the caregiving role. In addition to financial burdens, caregivers experience psychological distress and adverse health outcomes, including higher rates of hypertension and heart disease. These burdens differ by caregiver ethnicity, age, and rurality. Ethnic minority caregivers have reported more depression, lower use of support services, and worse physical health than Whites. African American caregivers report lower levels of depression but worse physical health. Caregiver age also plays a role in physical health burden, with older caregiver age shown to be negatively associated with caregiver physical functioning, bodily pain, vitality, and general health perception. This association is directly relevant to living kidney donation, as the prevalence of donors who are 65 years or older has increased from < 1% in 1998 to 5.6% in 2019 (based on OPTN data as of 3/23/2020). Rural caregivers report greater financial burden than their urban counterparts, of particular concern in the Deep South, where nearly two-thirds of all counties are rural.~When caregivers have their own underlying health issues, such as obesity, burdens may be further magnified when the caregiver becomes a patient, simultaneously requiring their own care while caring for another (e.g. obese living kidney donors who are the primary caregiver for their transplant recipient). Approximately 20% of living kidney donors are parents and significant others, individuals who often serve as the recipient's primary caregiver. Moreover, obese donors are at higher risk of post-donation disease development, including end-stage renal disease, diabetes, and hypertension. As donor selection criteria have expanded to include more obese individuals, these burdens impact high volume transplant centers in the Deep South that serve largely minority and rural populations. Comorbidity, such as obesity, in caregiver donors may increase the need for healthcare utilization, further exacerbating financial burdens, interfering with caregiver responsibilities, and subsequently impacting the recipient's health outcomes. To date, it is unknown whether the burdens of being an obese caregiver living donor are associated with healthcare utilization post-donation compared to non-caregivers and whether donor age, race, and rurality modify this relationship. This study is ancillary to an NIH-funded retrospective cohort study of living kidney donors with obesity (1R01DK113980) and will leverage the infrastructure of this R01 to explore the primary exposure of caregiving within this cohort.

The Role of Caregiving in Healthcare Utilization Among Obese Living Kidney Donors

Utilization, Health Care, Obesity

* Other: Caregivers * Other: Non-caregivers

Inclusion Criteria:~Age 18 years or greater~Underwent living donor nephrectomy at a transplant center in the United States between 1968 to present~Obesity: had a body mass index of 30 kg/m2 or greater at time of kidney donation~Exclusion Criteria:~Age < 18 years~Non-obese at time of donation~Does not consent to study participation

18 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Emergency department utilization | Proportion self-reporting at least one visit to the emergency department since donation/previous questionnaire | Baseline (kidney donation) through 40 years | | Hospital admission | Proportion self-reporting at least one hospital admission since donation/previous questionnaire | Baseline (kidney donation) through 40 years |

living kidney donor

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Caregivers<br>Prior obese living kidney donors who served as the primary caregiver for their recipient | Other: Caregivers<br>* Individuals who cared for themselves and their transplant recipient before and after kidney donation<br>| | Non-caregivers<br>Prior obese living kidney donors who were not the primary caregiver for their recipient | Other: Non-caregivers<br>* Individuals who donated a kidney as a living donor but did not serve as the primary caregiver for their recipient<br>|

Healthcare Utilization in Obese Caregiver Living Donors Study Overview ================= Brief Summary ----------------- The goal of this study is to estimate risk of post-donation healthcare use attributable to informal caregiving among obese living donors. Improving our understanding of the relationship between caregiving, donation, and healthcare use will allow us to improve living donor informed consent and post-donation care, particularly among older donors and those of minority race/ethnicity. Detailed Description ----------------- Caregiver burden is a well-known issue of primary caregiving for individuals with chronic disease, including transplant candidates and recipients. Informal caregiving is associated with an estimated $306 billion in unpaid labor costs and an average of $7,000 in out-of-pocket expenses related to the caregiving role. In addition to financial burdens, caregivers experience psychological distress and adverse health outcomes, including higher rates of hypertension and heart disease. These burdens differ by caregiver ethnicity, age, and rurality. Ethnic minority caregivers have reported more depression, lower use of support services, and worse physical health than Whites. African American caregivers report lower levels of depression but worse physical health. Caregiver age also plays a role in physical health burden, with older caregiver age shown to be negatively associated with caregiver physical functioning, bodily pain, vitality, and general health perception. This association is directly relevant to living kidney donation, as the prevalence of donors who are 65 years or older has increased from < 1% in 1998 to 5.6% in 2019 (based on OPTN data as of 3/23/2020). Rural caregivers report greater financial burden than their urban counterparts, of particular concern in the Deep South, where nearly two-thirds of all counties are rural. When caregivers have their own underlying health issues, such as obesity, burdens may be further magnified when the caregiver becomes a patient, simultaneously requiring their own care while caring for another (e.g. obese living kidney donors who are the primary caregiver for their transplant recipient). Approximately 20% of living kidney donors are parents and significant others, individuals who often serve as the recipient's primary caregiver. Moreover, obese donors are at higher risk of post-donation disease development, including end-stage renal disease, diabetes, and hypertension. As donor selection criteria have expanded to include more obese individuals, these burdens impact high volume transplant centers in the Deep South that serve largely minority and rural populations. Comorbidity, such as obesity, in caregiver donors may increase the need for healthcare utilization, further exacerbating financial burdens, interfering with caregiver responsibilities, and subsequently impacting the recipient's health outcomes. To date, it is unknown whether the burdens of being an obese caregiver living donor are associated with healthcare utilization post-donation compared to non-caregivers and whether donor age, race, and rurality modify this relationship. This study is ancillary to an NIH-funded retrospective cohort study of living kidney donors with obesity (1R01DK113980) and will leverage the infrastructure of this R01 to explore the primary exposure of caregiving within this cohort. Official Title ----------------- The Role of Caregiving in Healthcare Utilization Among Obese Living Kidney Donors Conditions ----------------- Utilization, Health Care, Obesity Intervention / Treatment ----------------- * Other: Caregivers * Other: Non-caregivers Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 18 years or greater Underwent living donor nephrectomy at a transplant center in the United States between 1968 to present Obesity: had a body mass index of 30 kg/m2 or greater at time of kidney donation Exclusion Criteria: Age < 18 years Non-obese at time of donation Does not consent to study participation Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Caregivers<br>Prior obese living kidney donors who served as the primary caregiver for their recipient | Other: Caregivers<br>* Individuals who cared for themselves and their transplant recipient before and after kidney donation<br>| | Non-caregivers<br>Prior obese living kidney donors who were not the primary caregiver for their recipient | Other: Non-caregivers<br>* Individuals who donated a kidney as a living donor but did not serve as the primary caregiver for their recipient<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Emergency department utilization | Proportion self-reporting at least one visit to the emergency department since donation/previous questionnaire | Baseline (kidney donation) through 40 years | | Hospital admission | Proportion self-reporting at least one hospital admission since donation/previous questionnaire | Baseline (kidney donation) through 40 years | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- living kidney donor

NCT02902406

Validation of DNA Methylation Biomarkers for Oral Cancer Detection-Follow up Study

This is a follow up study which aims to evaluate the correlation between several methylated genes (potential biomarkers) and oral cancers. A prospective case control trial is designed with sample size of at least 300 cases with estimated 200 subjects with precancerous lesion or oral cancer, and 100 subjects with normal oral mucosa. This study is approved by the National Taiwan University Hospital Research Ethics Committee. After signing the informed consent, all subjects will receive an intraoral examination and followed by epithelial cells collection with oral swab. The gDNA will be extracted from the oral swab collected cells and followed by bisulfite conversion procedures. Subsequently, bisulfite converted DNA will be subjected to methylated gene detection by Real-Time PCR. The methylation index (clinical sensitivity and specificity) of oral cancer related genes will be evaluated. For diagnosis confirmation, photos and biopsy specimens will be taken upon observation of abnormal lesion.

Validation of DNA Methylation Biomarkers for Oral Cancer Detection-Follow up Study

Oral Cancer

Inclusion Criteria:~Subject with age over 20.~Subjects with oral mucosal findings (normal, oral mucosal lichen planus, precancerous lesion, and oral cancer) or subjects who have involved in the previous study (NCT01945697).~Subjects agrees to sign the informed consent form.~Exclusion Criteria:~Pregnant woman.~Subject disagrees to sign the informed consent form.

20 Years

All

Accepts Healthy Volunteers

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | DNA methylation | | 2 years |

Mouth Neoplasms, Lip Neoplasms, Head and Neck Neoplasms, Neoplasms by Site, Neoplasms, Mouth Diseases, Stomatognathic Diseases, Lip Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | normal oral mucosa<br> | | | oral precancerous lesion or oral cancer<br> | |

Validation of DNA Methylation Biomarkers for Oral Cancer Detection-Follow up Study Study Overview ================= Brief Summary ----------------- This is a follow up study which aims to evaluate the correlation between several methylated genes (potential biomarkers) and oral cancers. A prospective case control trial is designed with sample size of at least 300 cases with estimated 200 subjects with precancerous lesion or oral cancer, and 100 subjects with normal oral mucosa. This study is approved by the National Taiwan University Hospital Research Ethics Committee. After signing the informed consent, all subjects will receive an intraoral examination and followed by epithelial cells collection with oral swab. The gDNA will be extracted from the oral swab collected cells and followed by bisulfite conversion procedures. Subsequently, bisulfite converted DNA will be subjected to methylated gene detection by Real-Time PCR. The methylation index (clinical sensitivity and specificity) of oral cancer related genes will be evaluated. For diagnosis confirmation, photos and biopsy specimens will be taken upon observation of abnormal lesion. Official Title ----------------- Validation of DNA Methylation Biomarkers for Oral Cancer Detection-Follow up Study Conditions ----------------- Oral Cancer Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Subject with age over 20. Subjects with oral mucosal findings (normal, oral mucosal lichen planus, precancerous lesion, and oral cancer) or subjects who have involved in the previous study (NCT01945697). Subjects agrees to sign the informed consent form. Exclusion Criteria: Pregnant woman. Subject disagrees to sign the informed consent form. Ages Eligible for Study ----------------- Minimum Age: 20 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | normal oral mucosa<br> | | | oral precancerous lesion or oral cancer<br> | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | DNA methylation | | 2 years |

NCT03660839

Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria

Primary Objective:~To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK) predictor.~Secondary Objectives:~To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR.~To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR.~To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints.~To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone.~To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood.

The duration of the study was up to 32 days, including up to 1 day screening period before the single-dose treatment, 5 days of post-treatment surveillance (included 2 to 4 days hospitalization) and 24±2 days follow-up period.

A Randomized, Open Label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 Dose Levels of Artefenomel (OZ439) Given in Combination With Ferroquine (FQ) and FQ Alone, in African Patients With Uncomplicated Plasmodium Falciparum Malaria

Plasmodium Falciparum Infection

* Drug: Artefenomel (OZ439) * Drug: Ferroquine (SSR97193)

Inclusion criteria :~Participants (14-69 years old inclusive) with body weight within 35 and 90 kilograms (kg), with uncomplicated Plasmodium falciparum (P. falciparum) malaria, with a fever as defined with axillary temperature greater than or equal to (>=) 37.5 degree Celsius (°C) or oral/ rectal/ tympanic temperature >=38°C or history of fever in the previous 24 hours (history of fever was documented), with a mono-infection with P. falciparum and parasitemia (microscopically, blood smear) >= 3,000 and less than or equal to (<=) 50,000 asexual parasites per microliter of blood.~Exclusion criteria:~Presence of severe malaria.~Known history or evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, respiratory, endocrine, immunological, infectious, neurological (in particular convulsions), malignancy, psychiatric disease or symptoms which, in the judgment of the investigator, might confuse the interpretation of the safety information.~Severe vomiting defined as more than 3 times in the 24 hours prior to enrollment in the study or inability to tolerate oral treatment or severe diarrhea defined as 3 or more watery stools per day.~Severe malnutrition defined as a body mass index of less than 16 kg per meter square for adults and for children Z-score less than (<) -3 or weight for age (%) of the median <60.~Splenectomized participants or presence of surgical scar on left hypochondrium.~Known history of hypersensitivity, allergic, or anaphylactoid reactions to FQ or other amino quinolines or to OZ439 or OZ277 or any of the excipients.~Participant treated with anti-malarial treatment:~With piperaquine phosphate-based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine within the previous 6 weeks.~With amodiaquine or chloroquine within the previous 4 weeks.~With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days.~With any herbal products or traditional medicines, within the past 7 days.~Previous treatment within 5 times the half-life or within the last 14 days, whichever the longest, which were: strong Cytochrome P450 (CYP) 2C or CYP3A inhibitors and/or moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers.~Any treatment known to induce a prolongation of QT interval.~Participated in any trial investigating OZ439 and/or FQ compounds.~Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance.~Enrolled in another clinical trial within the past 4 weeks or during the study period.~Mixed Plasmodium infection.~Presence of Hepatitis A - immunoglobulin, Hepatitis B surface antigen or Hepatitis C virus antibody and/or known to had active Hepatitis C virus ribonucleic acid.~Laboratory parameters with abnormalities deemed clinically significant by the investigator.~Abnormal Liver Function Test: aspartate transferase greater than (>) 2 upper limit of normal range (ULN), or alanine transferase >2 ULN or total bilirubin >1.5 ULN.~Positive pregnancy test at study screening for female participants of childbearing potential.~QT interval corrected using Fridericia formula (QTcF) >450 milliseconds at screening or pre-dose.~Hypokalemia (<3.5 millimoles per liter [mmol/L]), hypocalcemia (<2.0 mmol/L) or hypomagnesemia (<0.5 mmol/L) at screening or pre-dose.~Family history of sudden death or of congenital prolongation of the QT interval or known congenital prolongation of the QT-interval or any clinical condition known to prolong the QT interval e.g., participants with a history of symptomatic cardiac arrhythmias including atrial fibrillation or with clinically relevant bradycardia.~Participant not suitable for participation, whatever the reason, as judged by the Investigator, included medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures or unable to drink.~The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

14 Years

69 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28) | ACPR:absence of parasitemia at Day 28, irrespective of axillary temperature(AT), participants not meeting any criteria of early therapy failure(ETF):Danger signs(DS)/symptoms of complicated(SoC)/severe malaria(SM) at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia;or parasitemia on Day 2 >Day 0 irrespective of AT;or parasitemia on Day 3 with AT>=37.5 degree Celsius (°C);or parasitemia count on Day 3 >=25 percent (%) on Day 0, or late clinical failure (LCF):DS/SM in presence of parasitemia between Day 4 and 28,concomitant to at least one positive parasitemia;or presence of parasitemia and AT>=37.5°C on Day 4 to Day 28, or late parasitological failure(LPF):presence of parasitemia between Day 7 and 28 and AT<37.5°C and without rescue therapy. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with reinfection. | Day 28 |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28 | ACPR: absence of parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS/SoC/SM at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia; or parasitemia on Day 2 > Day 0 irrespective of AT; or parasitemia on Day 3 with AT >=37.5°C; or parasitemia count on Day 3 >=25% on Day 0, or LCF: DS/SM in presence of parasitemia between Day 4 and 28, concomitant to at least one positive parasitemia; or presence of parasitemia and AT>=37.5°C on Day 4 to Day 28, or LPF: presence of parasitemia between Day 7 and 28 and AT<37.5°C or having rescue therapy for malaria. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish reinfection (new clone of parasite) or recrudescence. | Day 28 | | Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours | Parasitemia (quantitative content of parasites present in the blood) at baseline until Day 7 (i.e. 168 hours) was assessed by optical microscope. | Baseline, 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post-dose | | Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours | The observed PRR was defined as the ratio of the number of parasites at time t=0 (baseline) divided by the parasite count at each specified time t (post-treatment). If the post dose parasite count = 0 (due to a negative parasitemia) then a value of 1 parasite per microliter was imputed to allow a parasite reduction ratio calculation. | Baseline, 24, 48 and 72 hours post-dose | | Time to 50% and 99% Parasite Reduction | Time to 50% and 99% parasite reduction was defined as time needed for the parasitemia (quantitative content of parasites present in blood) to be reduced to 50% and 99% of the initial value, respectively. | Up to Day 28 | | Parasite Clearance Time (PCT) | PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites by microscopy). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. If the second film was performed <6 hours or >12 hours of the first film, then the parasite clearance was confirmed or invalidated by the third (thick) film following the second one, whatever the timing of this third film: If the third film was negative, then the clearance was considered confirmed and if the third film was positive, then the clearance was invalidated. Kaplan-Meier method was used for the estimation. | From the start of study drug administration up to the time of the first negative blood film (up to Day 28) | | Parasite Clearance Rate | Parasite clearance rate (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite Clearance Estimator. | Up to Day 28 | | Time to Re-emergence | Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Re-emergence was confirmed by microscopy (positive blood smear). Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation. | Up to Day 28 | | Time to Recrudescence | Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation. | Up to Day 28 | | Time to Re-infection | Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differed from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Maier method was used for estimation. | Up to Day 28 | | Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia | The time elapsed below LOQ (LOQ expressed in parasites/microliter) of parasitemia (quantitative content of parasites present in the blood) was defined as the time (in days) for which no parasites were seen i.e., time corresponding to PCT, up to the time of occurrence of a new malaria infection or recrudescence. If there was no occurrence of a new malaria infection or recrudescence, then this was the time corresponding to the first negative thick blood film, until the end of study. PCT (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite clearance estimator. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Meier method was used for estimation. | Up to Day 28 | | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI) | An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of study drug up to the Day 28. AE of special interest (AESI) was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. | From Baseline up to Day 28 | | Pharmacokinetics (PK): Concentration of OZ439 in Plasma | Concentrations of OZ439 in plasma was analyzed by liquid chromatography tandem mass spectroscopy (LC-MS/MS). The lower limit of quantification (LLOQ) was 1 nanograms per milliliter for analysis of OZ439. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose | | Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood | Concentrations of FQ and SSR97213 in blood was analyzed by LC-MS/MS. The LLOQ was 5 nanograms per milliliter for analysis of FQ and SSR97213. | 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose | | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel | Cmax is the maximum observed plasma concentration of Artefenomel. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose | | Pharmacokinetics: Time to Reach Maximum Plasma Concentration (Tmax) of Artefenomel | tmax is the time taken by the drug to reach the maximum plasma concentration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose | | Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel | The observed plasma concentration of artefenomel post 168 hours of drug administration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | At 168 hours post-dose | | Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel | Area under the plasma concentration versus time curve from time 0 to infinity. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose | | Pharmacokinetics: Terminal Half-life (t1/2) of Artefenomel | Terminal t1/2 is defined as the time required for the plasma concentration of a drug to decrease by half of its initial concentration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose | | Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213 | Cmax is the maximum observed plasma concentration of Ferroquine. | Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose | | Pharmacokinetics: Time to Reach Maximum Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213 | tmax is the time taken by the drug to reach the maximum plasma concentration. | Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose | | Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213 | The observed plasma concentration of FQ and SSR97213 post 168 hours of FQ administration. | At 168 hours post-dose | | Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213 | Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours). | Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose | | Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213 | Area under the plasma concentration versus time curve from time 0 to infinity. | Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose | | Pharmacokinetics: Terminal Half-life of Ferroquine | Terminal t1/2 is defined as the time required for the plasma concentration of a drug to decrease by half of its initial concentration. | Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose |

Artefenomel, Ferroquine, Antimalarials, Antiprotozoal Agents, Antiparasitic Agents, Anti-Infective Agents

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Ferroquine 400 milligram (mg)<br>On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition. | Drug: Ferroquine (SSR97193)<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>| | Experimental: Ferroquine 400 mg + Artefenomel 300 mg<br>On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension. | Drug: Artefenomel (OZ439)<br>* Pharmaceutical form: Granules for oral suspension Route of administration: Oral<br>Drug: Ferroquine (SSR97193)<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>| | Experimental: Ferroquine 400 mg + Artefenomel 600 mg<br>On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension. | Drug: Artefenomel (OZ439)<br>* Pharmaceutical form: Granules for oral suspension Route of administration: Oral<br>Drug: Ferroquine (SSR97193)<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>| | Experimental: Ferroquine 400 mg + Artefenomel 1000 mg<br>On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension. | Drug: Artefenomel (OZ439)<br>* Pharmaceutical form: Granules for oral suspension Route of administration: Oral<br>Drug: Ferroquine (SSR97193)<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>|

Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria Study Overview ================= Brief Summary ----------------- Primary Objective: To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK) predictor. Secondary Objectives: To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR. To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR. To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints. To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone. To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood. Detailed Description ----------------- The duration of the study was up to 32 days, including up to 1 day screening period before the single-dose treatment, 5 days of post-treatment surveillance (included 2 to 4 days hospitalization) and 24±2 days follow-up period. Official Title ----------------- A Randomized, Open Label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 Dose Levels of Artefenomel (OZ439) Given in Combination With Ferroquine (FQ) and FQ Alone, in African Patients With Uncomplicated Plasmodium Falciparum Malaria Conditions ----------------- Plasmodium Falciparum Infection Intervention / Treatment ----------------- * Drug: Artefenomel (OZ439) * Drug: Ferroquine (SSR97193) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria : Participants (14-69 years old inclusive) with body weight within 35 and 90 kilograms (kg), with uncomplicated Plasmodium falciparum (P. falciparum) malaria, with a fever as defined with axillary temperature greater than or equal to (>=) 37.5 degree Celsius (°C) or oral/ rectal/ tympanic temperature >=38°C or history of fever in the previous 24 hours (history of fever was documented), with a mono-infection with P. falciparum and parasitemia (microscopically, blood smear) >= 3,000 and less than or equal to (<=) 50,000 asexual parasites per microliter of blood. Exclusion criteria: Presence of severe malaria. Known history or evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, respiratory, endocrine, immunological, infectious, neurological (in particular convulsions), malignancy, psychiatric disease or symptoms which, in the judgment of the investigator, might confuse the interpretation of the safety information. Severe vomiting defined as more than 3 times in the 24 hours prior to enrollment in the study or inability to tolerate oral treatment or severe diarrhea defined as 3 or more watery stools per day. Severe malnutrition defined as a body mass index of less than 16 kg per meter square for adults and for children Z-score less than (<) -3 or weight for age (%) of the median <60. Splenectomized participants or presence of surgical scar on left hypochondrium. Known history of hypersensitivity, allergic, or anaphylactoid reactions to FQ or other amino quinolines or to OZ439 or OZ277 or any of the excipients. Participant treated with anti-malarial treatment: With piperaquine phosphate-based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine within the previous 6 weeks. With amodiaquine or chloroquine within the previous 4 weeks. With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days. With any herbal products or traditional medicines, within the past 7 days. Previous treatment within 5 times the half-life or within the last 14 days, whichever the longest, which were: strong Cytochrome P450 (CYP) 2C or CYP3A inhibitors and/or moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers. Any treatment known to induce a prolongation of QT interval. Participated in any trial investigating OZ439 and/or FQ compounds. Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance. Enrolled in another clinical trial within the past 4 weeks or during the study period. Mixed Plasmodium infection. Presence of Hepatitis A - immunoglobulin, Hepatitis B surface antigen or Hepatitis C virus antibody and/or known to had active Hepatitis C virus ribonucleic acid. Laboratory parameters with abnormalities deemed clinically significant by the investigator. Abnormal Liver Function Test: aspartate transferase greater than (>) 2 upper limit of normal range (ULN), or alanine transferase >2 ULN or total bilirubin >1.5 ULN. Positive pregnancy test at study screening for female participants of childbearing potential. QT interval corrected using Fridericia formula (QTcF) >450 milliseconds at screening or pre-dose. Hypokalemia (<3.5 millimoles per liter [mmol/L]), hypocalcemia (<2.0 mmol/L) or hypomagnesemia (<0.5 mmol/L) at screening or pre-dose. Family history of sudden death or of congenital prolongation of the QT interval or known congenital prolongation of the QT-interval or any clinical condition known to prolong the QT interval e.g., participants with a history of symptomatic cardiac arrhythmias including atrial fibrillation or with clinically relevant bradycardia. Participant not suitable for participation, whatever the reason, as judged by the Investigator, included medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures or unable to drink. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. Ages Eligible for Study ----------------- Minimum Age: 14 Years Maximum Age: 69 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Ferroquine 400 milligram (mg)<br>On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition. | Drug: Ferroquine (SSR97193)<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>| | Experimental: Ferroquine 400 mg + Artefenomel 300 mg<br>On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension. | Drug: Artefenomel (OZ439)<br>* Pharmaceutical form: Granules for oral suspension Route of administration: Oral<br>Drug: Ferroquine (SSR97193)<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>| | Experimental: Ferroquine 400 mg + Artefenomel 600 mg<br>On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension. | Drug: Artefenomel (OZ439)<br>* Pharmaceutical form: Granules for oral suspension Route of administration: Oral<br>Drug: Ferroquine (SSR97193)<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>| | Experimental: Ferroquine 400 mg + Artefenomel 1000 mg<br>On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension. | Drug: Artefenomel (OZ439)<br>* Pharmaceutical form: Granules for oral suspension Route of administration: Oral<br>Drug: Ferroquine (SSR97193)<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28) | ACPR:absence of parasitemia at Day 28, irrespective of axillary temperature(AT), participants not meeting any criteria of early therapy failure(ETF):Danger signs(DS)/symptoms of complicated(SoC)/severe malaria(SM) at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia;or parasitemia on Day 2 >Day 0 irrespective of AT;or parasitemia on Day 3 with AT>=37.5 degree Celsius (°C);or parasitemia count on Day 3 >=25 percent (%) on Day 0, or late clinical failure (LCF):DS/SM in presence of parasitemia between Day 4 and 28,concomitant to at least one positive parasitemia;or presence of parasitemia and AT>=37.5°C on Day 4 to Day 28, or late parasitological failure(LPF):presence of parasitemia between Day 7 and 28 and AT<37.5°C and without rescue therapy. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with reinfection. | Day 28 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28 | ACPR: absence of parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS/SoC/SM at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia; or parasitemia on Day 2 > Day 0 irrespective of AT; or parasitemia on Day 3 with AT >=37.5°C; or parasitemia count on Day 3 >=25% on Day 0, or LCF: DS/SM in presence of parasitemia between Day 4 and 28, concomitant to at least one positive parasitemia; or presence of parasitemia and AT>=37.5°C on Day 4 to Day 28, or LPF: presence of parasitemia between Day 7 and 28 and AT<37.5°C or having rescue therapy for malaria. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish reinfection (new clone of parasite) or recrudescence. | Day 28 | | Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours | Parasitemia (quantitative content of parasites present in the blood) at baseline until Day 7 (i.e. 168 hours) was assessed by optical microscope. | Baseline, 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post-dose | | Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours | The observed PRR was defined as the ratio of the number of parasites at time t=0 (baseline) divided by the parasite count at each specified time t (post-treatment). If the post dose parasite count = 0 (due to a negative parasitemia) then a value of 1 parasite per microliter was imputed to allow a parasite reduction ratio calculation. | Baseline, 24, 48 and 72 hours post-dose | | Time to 50% and 99% Parasite Reduction | Time to 50% and 99% parasite reduction was defined as time needed for the parasitemia (quantitative content of parasites present in blood) to be reduced to 50% and 99% of the initial value, respectively. | Up to Day 28 | | Parasite Clearance Time (PCT) | PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites by microscopy). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. If the second film was performed <6 hours or >12 hours of the first film, then the parasite clearance was confirmed or invalidated by the third (thick) film following the second one, whatever the timing of this third film: If the third film was negative, then the clearance was considered confirmed and if the third film was positive, then the clearance was invalidated. Kaplan-Meier method was used for the estimation. | From the start of study drug administration up to the time of the first negative blood film (up to Day 28) | | Parasite Clearance Rate | Parasite clearance rate (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite Clearance Estimator. | Up to Day 28 | | Time to Re-emergence | Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Re-emergence was confirmed by microscopy (positive blood smear). Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation. | Up to Day 28 | | Time to Recrudescence | Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation. | Up to Day 28 | | Time to Re-infection | Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differed from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Maier method was used for estimation. | Up to Day 28 | | Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia | The time elapsed below LOQ (LOQ expressed in parasites/microliter) of parasitemia (quantitative content of parasites present in the blood) was defined as the time (in days) for which no parasites were seen i.e., time corresponding to PCT, up to the time of occurrence of a new malaria infection or recrudescence. If there was no occurrence of a new malaria infection or recrudescence, then this was the time corresponding to the first negative thick blood film, until the end of study. PCT (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite clearance estimator. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Meier method was used for estimation. | Up to Day 28 | | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI) | An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of study drug up to the Day 28. AE of special interest (AESI) was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. | From Baseline up to Day 28 | | Pharmacokinetics (PK): Concentration of OZ439 in Plasma | Concentrations of OZ439 in plasma was analyzed by liquid chromatography tandem mass spectroscopy (LC-MS/MS). The lower limit of quantification (LLOQ) was 1 nanograms per milliliter for analysis of OZ439. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose | | Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood | Concentrations of FQ and SSR97213 in blood was analyzed by LC-MS/MS. The LLOQ was 5 nanograms per milliliter for analysis of FQ and SSR97213. | 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose | | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel | Cmax is the maximum observed plasma concentration of Artefenomel. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose | | Pharmacokinetics: Time to Reach Maximum Plasma Concentration (Tmax) of Artefenomel | tmax is the time taken by the drug to reach the maximum plasma concentration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose | | Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel | The observed plasma concentration of artefenomel post 168 hours of drug administration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | At 168 hours post-dose | | Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel | Area under the plasma concentration versus time curve from time 0 to infinity. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose | | Pharmacokinetics: Terminal Half-life (t1/2) of Artefenomel | Terminal t1/2 is defined as the time required for the plasma concentration of a drug to decrease by half of its initial concentration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered. | Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose | | Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213 | Cmax is the maximum observed plasma concentration of Ferroquine. | Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose | | Pharmacokinetics: Time to Reach Maximum Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213 | tmax is the time taken by the drug to reach the maximum plasma concentration. | Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose | | Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213 | The observed plasma concentration of FQ and SSR97213 post 168 hours of FQ administration. | At 168 hours post-dose | | Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213 | Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours). | Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose | | Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213 | Area under the plasma concentration versus time curve from time 0 to infinity. | Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose | | Pharmacokinetics: Terminal Half-life of Ferroquine | Terminal t1/2 is defined as the time required for the plasma concentration of a drug to decrease by half of its initial concentration. | Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose |

NCT02731014

Dry Needling for Patients With Neck Pain

The aim of this trial will be to examine the short and long term effectiveness of dry needling on pain, disability, and patient perceived improvements in patients with neck pain attending physical therapy. The investigators hypothesize that patients who receive dry needling, manual therapy, and exercise will achieve greater reductions in pain and disability in the short (4 weeks) and long term (6 and 12 months) compared to those who receive sham dry needling, manual therapy, and exercise.

Background: Neck pain is a costly and common problem. Current treatments are not adequately effective for a large proportion of patients who continue to experience recurrent pain. Therefore, new treatment strategies should be investigated in an attempt to reduce the disability and high costs associated with neck pain.~Dry needling is a technique in which a fine needle is used to penetrate the skin, subcutaneous tissues, and muscle with the intent to mechanically disrupt tissue without the use of an anesthetic. Dry needling is emerging as a treatment modality that is widely used clinically to address a variety of musculoskeletal conditions. Recent studies of dry needling in mechanical neck pain have shown decreased pain, increased pain pressure threshold, improved range of motion, and decreased disability in the short term. The majority of these studies examined dry needling using methods atypical to clinical practice (dry needling as a sole treatment, or fewer visits than is common practice). None included long-term follow up. A clinical trial with realistic treatment time frames and methods consistent with clinical practice is needed to examine the effectiveness of dry needling on reducing pain and enhancing function in patients presenting with mechanical neck pain.~Purpose: The aim of this trial will be to examine the short and long term effectiveness of dry needling on pain, disability, and patient perceived improvements in patients with neck pain.~Design: The investigators will conduct a randomized single blind placebo controlled trial in accordance with the CONSORT guidelines. All patients with mechanical neck pain referred to physical therapy will be screened for eligibility criteria. Participants will be randomized to receive 1) dry needling, manual therapy, and exercise or 2) sham dry needling, manual therapy and exercise. Participants will receive 7 treatments over a maximum of 4 weeks.~Methods: The primary outcome will be disability as measured by the Neck Disability Index. Pain and patient perceived improvement will also be recorded. Outcome measures will be assessed at 4 weeks, 6 months, and 12-months by an assessor who is blind to the group allocation of the participants to determine the short and long-term treatment effects.~Data Analysis: The investigators will examine the primary aim with a 2-way repeated-measures analysis of variance (ANOVA) with treatment group as the between subject variable and time as the within-subjects variable. The hypothesis of interest will be the 2-way group by time interaction.~Significance: The successful completion of this trial will provide evidence to demonstrate whether dry needling is effective for the management of mechanical neck pain when used in a combined treatment approach as is commonly practiced clinically.

Dry Needling for Patients With Neck Pain: A Randomized Clinical Trial

Neck Pain

* Other: Dry Needling * Other: Sham Dry Needling * Other: Manual Therapy * Other: Exercise

Inclusion Criteria:~Age between >18 years old~Primary complaint of neck pain~Neck Disability Index > 10 points=20%~Exclusion Criteria:~Red flags noted in the patient's Neck Medical Screening Questionnaire (i.e. tumor, fracture, metabolic diseases, Rheumatoid Arthritis, osteoporosis, prolonged history of steroid use, symptoms of vertebrobasilar insufficiency, pregnancy, cervical spinal stenosis, bilateral upper extremity symptoms etc.~Use of blood thinners~History of whiplash injury within the past six weeks~Evidence of central nervous system involvement, to include hyperreflexia, sensory disturbances in the hand, intrinsic muscle wasting of the hands, unsteadiness during walking, nystagmus, loss of visual acuity, impaired sensation of the face, altered taste, the presence of pathological reflexes (i.e. positive Hoffman's and/or Babinski reflexes), etc.~Two or more positive neurologic signs consistent with nerve root compression, including any two of the following:~Muscle weakness involving a major muscle group of the upper extremity~Diminished upper extremity muscle stretch reflex (biceps brachii, brachioradialis, or triceps)~Diminished or absent sensation to pinprick in any upper extremity dermatome~Prior surgery to the neck or thoracic spine~Chiropractic, Physical Therapy, or Acupuncture treatment for their neck pain in the last 12-months~Workers compensation or pending legal action regarding their neck pain~Insufficient English language skills to complete all questionnaires~Inability to comply with treatment and follow-up schedule

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from baseline on the Neck Disability Index (NDI) | The Neck Disability Index (NDI) was created to measure pain related disability associated with activities of daily living in people with neck pain. The NDI contains ten focused sections. The NDI is easy to complete and score. Each item is scored on a 6 point scale and can reach a maximum score of 5; therefore, the maximum score is 50. This score will calculated as a percentage, with higher scores indicating higher levels of disability. | 4 weeks, 6 months, 12 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from baseline on The Global Rating Of Change Scale (GROC) | The GROC is a 15-point scale used to quantify a patient's improvement with treatment or to record the clinical course of a condition over time. Patients are asked to describe their overall condition since the start of treatment until the present time with options ranging from -7 (a very great deal worse) to +7 (a very great deal better) and 0 being described as about the same. | 4 weeks, 6 months, 12 months | | Questionnaire used to assess blinding of patients to which needling intervention they received | Used to assess blinding of patients as to which dry needling intervention the received (real or sham). | 4 weeks | | Change from baseline on the Visual Analog Scale (VAS) Pain | The VAS is a single item measure of pain using a 100 mm horizontal line anchored on the left side of which represents no pain and the right side represents the worst pain imaginable. The VAS will be used to calculate change in pain score from baseline to 4 weeks, 6 months, and 12 months. | 4 weeks, 6 months, 12 months |

Dry Needling

Neck Pain, Pain, Neurologic Manifestations

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Dry Needling Group<br>Dry Needling, Manual Therapy, and Exercise. | Other: Dry Needling<br>* Dry Needling targeting the posterior musculature of the cervical and thoracic spine.<br>Other: Manual Therapy<br>* Manual Therapy(mobilization/ manipulation) to address joint mobility of the cervical and thoracic spine.<br>Other: Exercise<br>* Exercise designed to improve performance of both the deep neck flexor musculature as well as the scapular musculature. The exercise portion will also include a stretching program targeting the cervicothoracic muscles which have been placed in a shortened position as a result of poor postures.<br>| | Sham Comparator: Sham Dry Needling Group<br>Sham Dry Needling, Manual Therapy, and Exercise. | Other: Sham Dry Needling<br>* Sham Dry Needling performed with Park sham acupuncture needles (Acuprime, UK) will be used to perform sham dry-needling. The device consists of 2 plastic tubes that slide into one another and cause a pricking sensation when pushed against the skin.<br>Other: Manual Therapy<br>* Manual Therapy(mobilization/ manipulation) to address joint mobility of the cervical and thoracic spine.<br>Other: Exercise<br>* Exercise designed to improve performance of both the deep neck flexor musculature as well as the scapular musculature. The exercise portion will also include a stretching program targeting the cervicothoracic muscles which have been placed in a shortened position as a result of poor postures.<br>|

Dry Needling for Patients With Neck Pain Study Overview ================= Brief Summary ----------------- The aim of this trial will be to examine the short and long term effectiveness of dry needling on pain, disability, and patient perceived improvements in patients with neck pain attending physical therapy. The investigators hypothesize that patients who receive dry needling, manual therapy, and exercise will achieve greater reductions in pain and disability in the short (4 weeks) and long term (6 and 12 months) compared to those who receive sham dry needling, manual therapy, and exercise. Detailed Description ----------------- Background: Neck pain is a costly and common problem. Current treatments are not adequately effective for a large proportion of patients who continue to experience recurrent pain. Therefore, new treatment strategies should be investigated in an attempt to reduce the disability and high costs associated with neck pain. Dry needling is a technique in which a fine needle is used to penetrate the skin, subcutaneous tissues, and muscle with the intent to mechanically disrupt tissue without the use of an anesthetic. Dry needling is emerging as a treatment modality that is widely used clinically to address a variety of musculoskeletal conditions. Recent studies of dry needling in mechanical neck pain have shown decreased pain, increased pain pressure threshold, improved range of motion, and decreased disability in the short term. The majority of these studies examined dry needling using methods atypical to clinical practice (dry needling as a sole treatment, or fewer visits than is common practice). None included long-term follow up. A clinical trial with realistic treatment time frames and methods consistent with clinical practice is needed to examine the effectiveness of dry needling on reducing pain and enhancing function in patients presenting with mechanical neck pain. Purpose: The aim of this trial will be to examine the short and long term effectiveness of dry needling on pain, disability, and patient perceived improvements in patients with neck pain. Design: The investigators will conduct a randomized single blind placebo controlled trial in accordance with the CONSORT guidelines. All patients with mechanical neck pain referred to physical therapy will be screened for eligibility criteria. Participants will be randomized to receive 1) dry needling, manual therapy, and exercise or 2) sham dry needling, manual therapy and exercise. Participants will receive 7 treatments over a maximum of 4 weeks. Methods: The primary outcome will be disability as measured by the Neck Disability Index. Pain and patient perceived improvement will also be recorded. Outcome measures will be assessed at 4 weeks, 6 months, and 12-months by an assessor who is blind to the group allocation of the participants to determine the short and long-term treatment effects. Data Analysis: The investigators will examine the primary aim with a 2-way repeated-measures analysis of variance (ANOVA) with treatment group as the between subject variable and time as the within-subjects variable. The hypothesis of interest will be the 2-way group by time interaction. Significance: The successful completion of this trial will provide evidence to demonstrate whether dry needling is effective for the management of mechanical neck pain when used in a combined treatment approach as is commonly practiced clinically. Official Title ----------------- Dry Needling for Patients With Neck Pain: A Randomized Clinical Trial Conditions ----------------- Neck Pain Intervention / Treatment ----------------- * Other: Dry Needling * Other: Sham Dry Needling * Other: Manual Therapy * Other: Exercise Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age between >18 years old Primary complaint of neck pain Neck Disability Index > 10 points=20% Exclusion Criteria: Red flags noted in the patient's Neck Medical Screening Questionnaire (i.e. tumor, fracture, metabolic diseases, Rheumatoid Arthritis, osteoporosis, prolonged history of steroid use, symptoms of vertebrobasilar insufficiency, pregnancy, cervical spinal stenosis, bilateral upper extremity symptoms etc. Use of blood thinners History of whiplash injury within the past six weeks Evidence of central nervous system involvement, to include hyperreflexia, sensory disturbances in the hand, intrinsic muscle wasting of the hands, unsteadiness during walking, nystagmus, loss of visual acuity, impaired sensation of the face, altered taste, the presence of pathological reflexes (i.e. positive Hoffman's and/or Babinski reflexes), etc. Two or more positive neurologic signs consistent with nerve root compression, including any two of the following: Muscle weakness involving a major muscle group of the upper extremity Diminished upper extremity muscle stretch reflex (biceps brachii, brachioradialis, or triceps) Diminished or absent sensation to pinprick in any upper extremity dermatome Prior surgery to the neck or thoracic spine Chiropractic, Physical Therapy, or Acupuncture treatment for their neck pain in the last 12-months Workers compensation or pending legal action regarding their neck pain Insufficient English language skills to complete all questionnaires Inability to comply with treatment and follow-up schedule Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Dry Needling Group<br>Dry Needling, Manual Therapy, and Exercise. | Other: Dry Needling<br>* Dry Needling targeting the posterior musculature of the cervical and thoracic spine.<br>Other: Manual Therapy<br>* Manual Therapy(mobilization/ manipulation) to address joint mobility of the cervical and thoracic spine.<br>Other: Exercise<br>* Exercise designed to improve performance of both the deep neck flexor musculature as well as the scapular musculature. The exercise portion will also include a stretching program targeting the cervicothoracic muscles which have been placed in a shortened position as a result of poor postures.<br>| | Sham Comparator: Sham Dry Needling Group<br>Sham Dry Needling, Manual Therapy, and Exercise. | Other: Sham Dry Needling<br>* Sham Dry Needling performed with Park sham acupuncture needles (Acuprime, UK) will be used to perform sham dry-needling. The device consists of 2 plastic tubes that slide into one another and cause a pricking sensation when pushed against the skin.<br>Other: Manual Therapy<br>* Manual Therapy(mobilization/ manipulation) to address joint mobility of the cervical and thoracic spine.<br>Other: Exercise<br>* Exercise designed to improve performance of both the deep neck flexor musculature as well as the scapular musculature. The exercise portion will also include a stretching program targeting the cervicothoracic muscles which have been placed in a shortened position as a result of poor postures.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from baseline on the Neck Disability Index (NDI) | The Neck Disability Index (NDI) was created to measure pain related disability associated with activities of daily living in people with neck pain. The NDI contains ten focused sections. The NDI is easy to complete and score. Each item is scored on a 6 point scale and can reach a maximum score of 5; therefore, the maximum score is 50. This score will calculated as a percentage, with higher scores indicating higher levels of disability. | 4 weeks, 6 months, 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from baseline on The Global Rating Of Change Scale (GROC) | The GROC is a 15-point scale used to quantify a patient's improvement with treatment or to record the clinical course of a condition over time. Patients are asked to describe their overall condition since the start of treatment until the present time with options ranging from -7 (a very great deal worse) to +7 (a very great deal better) and 0 being described as about the same. | 4 weeks, 6 months, 12 months | | Questionnaire used to assess blinding of patients to which needling intervention they received | Used to assess blinding of patients as to which dry needling intervention the received (real or sham). | 4 weeks | | Change from baseline on the Visual Analog Scale (VAS) Pain | The VAS is a single item measure of pain using a 100 mm horizontal line anchored on the left side of which represents no pain and the right side represents the worst pain imaginable. The VAS will be used to calculate change in pain score from baseline to 4 weeks, 6 months, and 12 months. | 4 weeks, 6 months, 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Dry Needling

NCT05375942

This is a Retrospective Observational Study Looking at the Characteristics and Outcomes of Participants Taking Inflectra Using the CorEvitas Rheumatoid Arthritis Registry

This is a retrospective observational study looking at the characteristics and outcomes of participants taking Inflectra using the CorEvitas Rheumatoid Arthritis Registry.

Characteristics and 6-month Outcomes Among Real-World Rheumatoid Arthritis Patients Initiating Inflectra

Arthritis, Rheumatoid

* Drug: Inflectra * Drug: Inflectra

Inclusion Criteria:~Be at least 18 years of age~Have been diagnosed with RA by a rheumatologist~Have initiated treatment with Inflectra~Had assessment of effectiveness in patients who have at least one follow up visit.~Exclusion Criteria:~No additional exclusion criteria

18 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of participants achieving Low Disease Activity (LDA) | Response is defined as the achievement of LDA (CDAI≤10) among patients with moderate or high disease activity (CDAI>10).~CDAI = Clinical Disease Activity Index (Physician Global + Patient Global + tender joint count (TJC) + swollen joint count (SJC)) | Baseline to 6 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of participants achieving clinical remission | Clinical remission is defined as CDAI ≤ 2.8~Rate of response at follow up visit-achievement of remission (CDAI≤2.8) among patients with LDA, moderate, or high disease activity (CDAI>2.8) at baseline. | Baseline to 6 months | | Change in Clinical Disease Activity Index (CDAI) | Numerical change in CDAI from baseline. Increase in number signifies worsening, decrease in number signifies improvement | Baseline to 6 months | | Change in Health Assessment Questionnaire (HAQ) | Numerical change in HAQ (0-3) | Baseline to 6 months | | Change in patient pain | Numerical change in patient pain Visual Analogue Scale (VAS) (0-100) | Baseline to 6 months | | Change in patient fatigue | Numerical change in patient fatigue Visual Analogue Scale (VAS) (0-100) | Baseline to 6 months | | Achievement of mACR20 | Achievement of mACR20 response at 6 months~mACR20= Modified American College of Rheumatology 20 response is defined as an improvement of 20% or more from baseline in the number of tender joints (from an analysis of 68 joints), in the number of swollen joints (from an analysis of 66 joints), and in three of the following four domains: a patient's global assessment of arthritis activity, a physician's global assessment of arthritis activity, and a patient's assessment of arthritis pain (with all three evaluations measured on a visual-analogue scale of 0 to 100 mm, with higher scores indicating greater pain or disability); disability as measured by the HAQ-DI | Baseline to 6 months | | Achievement of mACR50 | Achievement of mACR50 response | Baseline to 6 months | | Achievement of mACR70 | Achievement of mACR70 response | Baseline to 6 months |

Infliximab, Tumor Necrosis Factor Inhibitors, Anti-Inflammatory Agents, Dermatologic Agents, Gastrointestinal Agents, Antirheumatic Agents

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | characteristics of patients newly initiated on Inflectra<br> | Drug: Inflectra<br>* 1. To describe the characteristics of patients newly initiated on Inflectra.<br>| | outcomes after initiating Inflectra<br> | Drug: Inflectra<br>* 2. To describe 6-month outcomes after initiating Inflectra, among patients who have 6 months follow-up information in the CorEvitas' RA Registry.<br>|

This is a Retrospective Observational Study Looking at the Characteristics and Outcomes of Participants Taking Inflectra Using the CorEvitas Rheumatoid Arthritis Registry Study Overview ================= Brief Summary ----------------- This is a retrospective observational study looking at the characteristics and outcomes of participants taking Inflectra using the CorEvitas Rheumatoid Arthritis Registry. Official Title ----------------- Characteristics and 6-month Outcomes Among Real-World Rheumatoid Arthritis Patients Initiating Inflectra Conditions ----------------- Arthritis, Rheumatoid Intervention / Treatment ----------------- * Drug: Inflectra * Drug: Inflectra Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Be at least 18 years of age Have been diagnosed with RA by a rheumatologist Have initiated treatment with Inflectra Had assessment of effectiveness in patients who have at least one follow up visit. Exclusion Criteria: No additional exclusion criteria Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | characteristics of patients newly initiated on Inflectra<br> | Drug: Inflectra<br>* 1. To describe the characteristics of patients newly initiated on Inflectra.<br>| | outcomes after initiating Inflectra<br> | Drug: Inflectra<br>* 2. To describe 6-month outcomes after initiating Inflectra, among patients who have 6 months follow-up information in the CorEvitas' RA Registry.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of participants achieving Low Disease Activity (LDA) | Response is defined as the achievement of LDA (CDAI≤10) among patients with moderate or high disease activity (CDAI>10). CDAI = Clinical Disease Activity Index (Physician Global + Patient Global + tender joint count (TJC) + swollen joint count (SJC)) | Baseline to 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of participants achieving clinical remission | Clinical remission is defined as CDAI ≤ 2.8 Rate of response at follow up visit-achievement of remission (CDAI≤2.8) among patients with LDA, moderate, or high disease activity (CDAI>2.8) at baseline. | Baseline to 6 months | | Change in Clinical Disease Activity Index (CDAI) | Numerical change in CDAI from baseline. Increase in number signifies worsening, decrease in number signifies improvement | Baseline to 6 months | | Change in Health Assessment Questionnaire (HAQ) | Numerical change in HAQ (0-3) | Baseline to 6 months | | Change in patient pain | Numerical change in patient pain Visual Analogue Scale (VAS) (0-100) | Baseline to 6 months | | Change in patient fatigue | Numerical change in patient fatigue Visual Analogue Scale (VAS) (0-100) | Baseline to 6 months | | Achievement of mACR20 | Achievement of mACR20 response at 6 months mACR20= Modified American College of Rheumatology 20 response is defined as an improvement of 20% or more from baseline in the number of tender joints (from an analysis of 68 joints), in the number of swollen joints (from an analysis of 66 joints), and in three of the following four domains: a patient's global assessment of arthritis activity, a physician's global assessment of arthritis activity, and a patient's assessment of arthritis pain (with all three evaluations measured on a visual-analogue scale of 0 to 100 mm, with higher scores indicating greater pain or disability); disability as measured by the HAQ-DI | Baseline to 6 months | | Achievement of mACR50 | Achievement of mACR50 response | Baseline to 6 months | | Achievement of mACR70 | Achievement of mACR70 response | Baseline to 6 months |

NCT05577702

Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations in Participants With Resectable Non-Small Cell Lung Cancer

This is a randomized, open-label, multicenter, Phase 2, umbrella study to evaluate the preliminary efficacy, safety, and pharmacodynamics of tislelizumab as monotherapy and in combination with investigational agents as neoadjuvant treatment in Chinese participants with resectable Stage II to IIIA non-small cell lung cancer (NSCLC). The study is designed with the flexibility of adding treatment arms as new treatments become available or discontinuing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and of modifying the participant population.

A Randomized, Open-Label, Multicenter, Phase 2, Umbrella Study to Evaluate the Preliminary Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations With and Without Chemotherapy as Neoadjuvant Treatment in Chinese Patients With Resectable Stage II to IIIA Non-Small Cell Lung Cancer

Non Small Cell Lung Cancer

* Drug: Tislelizumab * Drug: Ociperlimab * Drug: LBL-007 * Drug: Cisplatin * Drug: Carboplatin * Drug: Pemetrexed * Drug: Paclitaxel

Inclusion Criteria:~Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1~Histologically confirmed Stage II-IIIA NSCLC (per the Eighth American Joint Committee on Cancer/Union Internationale Contre le Cancer [NSCLC] staging system)~Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent~Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained ≤ 7 days before randomization~Provide formalin-fixed paraffin-embedded block (preferred) or at least 15 freshly cut unstained FFPE slides of the primary tumor for biomarker evaluation during screening~Exclusion Criteria:~Any prior antineoplastic therapy(ies) for current lung cancer (eg, radiotherapy, targeted therapies, ablation, or other systemic or local antineoplastic treatment)~Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-cell immunoglobulin and ITIM domain (TIGIT), anti-lymphocyte activation gene-3 (LAG-3), or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways~Has mixed small cell lung cancer~Participants with large cell neuroendocrine carcinoma (LCNEC)~The presence of locally advanced unresectable NSCLC regardless of stage or metastatic disease~Known EGFR sensitizing mutations and/or ALK rearrangement~NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Major Pathological Response (MPR) | MPR is defined as the proportion of participants with ≤ 10% residual viable tumor in the resected primary tumor and all resected lymph nodes as assessed by blinded independent pathology review (BIPR) | Up to approximately 18 weeks after first dose |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Pathological complete response (pCR) | pCR is defined as the proportion of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes as assessed by the BIPR | Up to approximately 18 weeks after first dose | | Event-free survival (EFS) | EFS is defined as the time from randomization until any of the following events, whichever occurs first: radiographic disease progression that precludes definitive surgery, local or distant recurrence, as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause | Up to approximately 2 years | | Overall survival (OS) | OS is defined as the time from the date of randomization to the date of death due to any cause | Up to approximately 2 years | | Disease-free survival (DFS) | DFS is defined as the time from the first date of no disease (ie, participants who underwent margin-negative [R0] resection) to local or distant recurrence, as assessed by the investigator according to RECIST v1.1, or death due to any cause, whichever occurs first | Up to approximately 2 years | | Number of participants with adverse events | Number of participants with treatment-emergent adverse events, including serious adverse events and immune-mediated adverse events (imAEs), with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 | Up to approximately 2 years | | Proportion of participants who undergo surgical resection | Proportion of participants who undergo surgical resection within a scheduled period after receiving any dose of investigational agents, delayed or canceled surgery, duration of surgery and surgical approach | Up to approximately 18 weeks after first dose | | Serum or plasma concentrations of investigational agents | | Up to 30 days after last dose | | Number of participants with anti-drug antibodies (ADAs) | | Up to 30 days after last dose |

Paclitaxel, Carboplatin, Pemetrexed, Tislelizumab, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action, Enzyme Inhibitors, Folic Acid Antagonists, Nucleic Acid Synthesis Inhibitors, Antineoplastic Agents, Immunological

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Arm 1A: Tislelizumab Monotherapy<br>Tislelizumab on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;| | Experimental: Arm 1B: Tislelizumab and Ociperlimab<br>Tislelizumab + ociperlimab on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: Ociperlimab<br>* Administered as an intravenous infusion<br>* Other names: BGB-A1217;| | Experimental: Arm 1C: Tislelizumab and LBL-007<br>Tislelizumab + LBL-007 on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: LBL-007<br>* Administered as an intravenous infusion<br>| | Experimental: Arm 2A: Tislelizumab and Chemotherapy<br>Tislelizumab + chemotherapy on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days); Platinum-based doublet chemotherapy options may include:~Cisplatin/carboplatin + pemetrexed (nonsquamous)~Cisplatin/carboplatin + paclitaxel (squamous) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: Cisplatin<br>* Administered as an intravenous infusion<br>Drug: Carboplatin<br>* Administered as an intravenous infusion<br>Drug: Pemetrexed<br>* Administered as an intravenous infusion<br>Drug: Paclitaxel<br>* Administered as an intravenous infusion<br>| | Experimental: Arm 2C: LBL-007 and Tislelizumab and Chemotherapy<br>LBL-007 + tislelizumab + chemotherapy on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days); Platinum-based doublet chemotherapy options may include:~Cisplatin/carboplatin + pemetrexed (nonsquamous)~Cisplatin/carboplatin + paclitaxel (squamous) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: LBL-007<br>* Administered as an intravenous infusion<br>Drug: Cisplatin<br>* Administered as an intravenous infusion<br>Drug: Carboplatin<br>* Administered as an intravenous infusion<br>Drug: Pemetrexed<br>* Administered as an intravenous infusion<br>Drug: Paclitaxel<br>* Administered as an intravenous infusion<br>|

Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations in Participants With Resectable Non-Small Cell Lung Cancer Study Overview ================= Brief Summary ----------------- This is a randomized, open-label, multicenter, Phase 2, umbrella study to evaluate the preliminary efficacy, safety, and pharmacodynamics of tislelizumab as monotherapy and in combination with investigational agents as neoadjuvant treatment in Chinese participants with resectable Stage II to IIIA non-small cell lung cancer (NSCLC). The study is designed with the flexibility of adding treatment arms as new treatments become available or discontinuing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and of modifying the participant population. Official Title ----------------- A Randomized, Open-Label, Multicenter, Phase 2, Umbrella Study to Evaluate the Preliminary Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations With and Without Chemotherapy as Neoadjuvant Treatment in Chinese Patients With Resectable Stage II to IIIA Non-Small Cell Lung Cancer Conditions ----------------- Non Small Cell Lung Cancer Intervention / Treatment ----------------- * Drug: Tislelizumab * Drug: Ociperlimab * Drug: LBL-007 * Drug: Cisplatin * Drug: Carboplatin * Drug: Pemetrexed * Drug: Paclitaxel Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 Histologically confirmed Stage II-IIIA NSCLC (per the Eighth American Joint Committee on Cancer/Union Internationale Contre le Cancer [NSCLC] staging system) Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained ≤ 7 days before randomization Provide formalin-fixed paraffin-embedded block (preferred) or at least 15 freshly cut unstained FFPE slides of the primary tumor for biomarker evaluation during screening Exclusion Criteria: Any prior antineoplastic therapy(ies) for current lung cancer (eg, radiotherapy, targeted therapies, ablation, or other systemic or local antineoplastic treatment) Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-cell immunoglobulin and ITIM domain (TIGIT), anti-lymphocyte activation gene-3 (LAG-3), or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways Has mixed small cell lung cancer Participants with large cell neuroendocrine carcinoma (LCNEC) The presence of locally advanced unresectable NSCLC regardless of stage or metastatic disease Known EGFR sensitizing mutations and/or ALK rearrangement NOTE: Other protocol defined Inclusion/Exclusion criteria may apply. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Arm 1A: Tislelizumab Monotherapy<br>Tislelizumab on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;| | Experimental: Arm 1B: Tislelizumab and Ociperlimab<br>Tislelizumab + ociperlimab on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: Ociperlimab<br>* Administered as an intravenous infusion<br>* Other names: BGB-A1217;| | Experimental: Arm 1C: Tislelizumab and LBL-007<br>Tislelizumab + LBL-007 on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: LBL-007<br>* Administered as an intravenous infusion<br>| | Experimental: Arm 2A: Tislelizumab and Chemotherapy<br>Tislelizumab + chemotherapy on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days); Platinum-based doublet chemotherapy options may include: Cisplatin/carboplatin + pemetrexed (nonsquamous) Cisplatin/carboplatin + paclitaxel (squamous) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: Cisplatin<br>* Administered as an intravenous infusion<br>Drug: Carboplatin<br>* Administered as an intravenous infusion<br>Drug: Pemetrexed<br>* Administered as an intravenous infusion<br>Drug: Paclitaxel<br>* Administered as an intravenous infusion<br>| | Experimental: Arm 2C: LBL-007 and Tislelizumab and Chemotherapy<br>LBL-007 + tislelizumab + chemotherapy on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days); Platinum-based doublet chemotherapy options may include: Cisplatin/carboplatin + pemetrexed (nonsquamous) Cisplatin/carboplatin + paclitaxel (squamous) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: LBL-007<br>* Administered as an intravenous infusion<br>Drug: Cisplatin<br>* Administered as an intravenous infusion<br>Drug: Carboplatin<br>* Administered as an intravenous infusion<br>Drug: Pemetrexed<br>* Administered as an intravenous infusion<br>Drug: Paclitaxel<br>* Administered as an intravenous infusion<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Major Pathological Response (MPR) | MPR is defined as the proportion of participants with ≤ 10% residual viable tumor in the resected primary tumor and all resected lymph nodes as assessed by blinded independent pathology review (BIPR) | Up to approximately 18 weeks after first dose | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Pathological complete response (pCR) | pCR is defined as the proportion of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes as assessed by the BIPR | Up to approximately 18 weeks after first dose | | Event-free survival (EFS) | EFS is defined as the time from randomization until any of the following events, whichever occurs first: radiographic disease progression that precludes definitive surgery, local or distant recurrence, as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause | Up to approximately 2 years | | Overall survival (OS) | OS is defined as the time from the date of randomization to the date of death due to any cause | Up to approximately 2 years | | Disease-free survival (DFS) | DFS is defined as the time from the first date of no disease (ie, participants who underwent margin-negative [R0] resection) to local or distant recurrence, as assessed by the investigator according to RECIST v1.1, or death due to any cause, whichever occurs first | Up to approximately 2 years | | Number of participants with adverse events | Number of participants with treatment-emergent adverse events, including serious adverse events and immune-mediated adverse events (imAEs), with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 | Up to approximately 2 years | | Proportion of participants who undergo surgical resection | Proportion of participants who undergo surgical resection within a scheduled period after receiving any dose of investigational agents, delayed or canceled surgery, duration of surgery and surgical approach | Up to approximately 18 weeks after first dose | | Serum or plasma concentrations of investigational agents | | Up to 30 days after last dose | | Number of participants with anti-drug antibodies (ADAs) | | Up to 30 days after last dose |

NCT02730754

Emotional Disorders and Outcomes in Adults With Type 2 Diabetes Mellitus at Primary Care

This study aims to determine which factors are related to change in diabetes-related distress and change in depressive symptoms after three years of follow-up in Asian adults with type 2 diabetes mellitus in primary care. The investigators will explore the impact of patient demographics, cardiometabolic control, medications adherence, health-related quality of life, self-efficacy and self-management behaviors on diabetes-related distress and depressive symptoms.

Patients with type 2 diabetes mellitus (T2DM) have been shown to experience psychological burden and distorted illness perception. These psychological burden include feeling of burned-out, fatigue, distress and depression, and in addition of distorted illness perception often lead to difficulty in coping with the demands of life-style changes and adherence to medication. Diabetes-related distress (DRD) and depressive symptoms (DS) were associated with glycaemic control and medication adherence, and life-styles behaviors, respectively. However, evidence on the relationships between DRD, DS and clinically significant outcomes are scarce in Asian adults with T2DM. Primary care patients who participated before will be re-invited. This is a repeated cross-sectional study of a cohorts of 700 patients who were first studied in 2013 (Emotional Distress in adults with type 2 Diabetes Mellitus & Quality of Life [EDDMQoL] study with the National Medical Research Register (NMRR) identification number: NMRR-12-1167-14158). Demographic data (age, gender, ethnicity, religion, educational level, occupation and monthly income), smoking status, self-perceive social support and health literacy will be collected by questionnaires.

Relationship Between Emotional Disorders (Diabetes Distress and Depression) and Outcomes (Self-care and Clinical) in Adults With Type 2 Diabetes Mellitus in Primary Care: A Retrospective Cohort Study

Type 2 Diabetes Mellitus

Inclusion Criteria:~Those who participated in the EDDMQoL study~Adults aged at least 30 year-old~Diagnosed of T2DM more than three years ago~On regular follow-up with at least three visits in the previous year~Exclusion Criteria:~Patients who are pregnant or lactating~Having psychiatric/psychological disorders that could impair judgments and memory~Patients who cannot read or understand English, Malay or Mandarin

30 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Diabetes-related distress measured with Diabetes Distress Scale-17 | Change in diabetes-related distress | Baseline and 3 year | | Depressive symptoms measured with Patient Health Questionnaire-9 | Change in depressive symptoms | Baseline and 3 year |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Diabetes-related distress and depression combined | Change in both diabetes-related distress and depressive symptoms combined | Baseline and 3 year | | Illness perceptions measured with Brief Illness Perception Questionnaire | Cross-sectional, an association with other variables | Through study completion | | Diabetes distress measured with Problem Areas in Diabetes Scale (PAID-5) | Cross-sectional, an association with other variables | Through study completion |

Mood Disorders, Illness Perception, Primary Care, Medication Adherence

Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases

Emotional Disorders and Outcomes in Adults With Type 2 Diabetes Mellitus at Primary Care Study Overview ================= Brief Summary ----------------- This study aims to determine which factors are related to change in diabetes-related distress and change in depressive symptoms after three years of follow-up in Asian adults with type 2 diabetes mellitus in primary care. The investigators will explore the impact of patient demographics, cardiometabolic control, medications adherence, health-related quality of life, self-efficacy and self-management behaviors on diabetes-related distress and depressive symptoms. Detailed Description ----------------- Patients with type 2 diabetes mellitus (T2DM) have been shown to experience psychological burden and distorted illness perception. These psychological burden include feeling of burned-out, fatigue, distress and depression, and in addition of distorted illness perception often lead to difficulty in coping with the demands of life-style changes and adherence to medication. Diabetes-related distress (DRD) and depressive symptoms (DS) were associated with glycaemic control and medication adherence, and life-styles behaviors, respectively. However, evidence on the relationships between DRD, DS and clinically significant outcomes are scarce in Asian adults with T2DM. Primary care patients who participated before will be re-invited. This is a repeated cross-sectional study of a cohorts of 700 patients who were first studied in 2013 (Emotional Distress in adults with type 2 Diabetes Mellitus & Quality of Life [EDDMQoL] study with the National Medical Research Register (NMRR) identification number: NMRR-12-1167-14158). Demographic data (age, gender, ethnicity, religion, educational level, occupation and monthly income), smoking status, self-perceive social support and health literacy will be collected by questionnaires. Official Title ----------------- Relationship Between Emotional Disorders (Diabetes Distress and Depression) and Outcomes (Self-care and Clinical) in Adults With Type 2 Diabetes Mellitus in Primary Care: A Retrospective Cohort Study Conditions ----------------- Type 2 Diabetes Mellitus Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Those who participated in the EDDMQoL study Adults aged at least 30 year-old Diagnosed of T2DM more than three years ago On regular follow-up with at least three visits in the previous year Exclusion Criteria: Patients who are pregnant or lactating Having psychiatric/psychological disorders that could impair judgments and memory Patients who cannot read or understand English, Malay or Mandarin Ages Eligible for Study ----------------- Minimum Age: 30 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Diabetes-related distress measured with Diabetes Distress Scale-17 | Change in diabetes-related distress | Baseline and 3 year | | Depressive symptoms measured with Patient Health Questionnaire-9 | Change in depressive symptoms | Baseline and 3 year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Diabetes-related distress and depression combined | Change in both diabetes-related distress and depressive symptoms combined | Baseline and 3 year | | Illness perceptions measured with Brief Illness Perception Questionnaire | Cross-sectional, an association with other variables | Through study completion | | Diabetes distress measured with Problem Areas in Diabetes Scale (PAID-5) | Cross-sectional, an association with other variables | Through study completion | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Mood Disorders, Illness Perception, Primary Care, Medication Adherence

NCT04784754

Dose-Ranging Study to Assess the Safety and Efficacy of Melatonin in Outpatients Infected With COVID-19

A pilot placebo-controlled randomized double-blind trial of Melatonin in outpatients with COVID-19 infection to evaluate Safety, Efficacy and Dose-ranging.

Studies have shown in the blood of patients with COVID-19 there was a marked increase in the cytokines and chemokines interleukin 1β (IL-1β), interferon-γ (IFN-γ), interferon-inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1) and interleukin-4 (IL-4). Consequently, treatments that reduce cytokine/chemokine production that result in a less severe course of disease could be potentially beneficial. Melatonin, a pineal hormone, has been shown to have anti-inflammation, anti-oxidation and immune enhancing features. In multiple animal models of lung injury, Melatonin supplementation has been shown to decrease the number of inflammatory cells, reduce the levels of the cytokines IL-4, IL-5, IL-13 and TNF-a and reduce nitric oxide and hydroxyl radical concentrations. We propose a dose ranging pilot study to assess the safety and efficacy of melatonin in reducing hospitalization in COVID-19 patients with mild-moderate disease. A total of 50 participants will be randomized to the intervention arm (melatonin: 3 mg, or 30 mg three times a day for 14 days) or control arm (placebo) in a 2:2:1 fashion using a permuted block randomization scheme. Analyses will be performed with a focus on estimation of specific clinically important parameters, including safety and preliminary evidence of activity, for planning of a subsequent definitive comparative trial designed to fully assess efficacy.

A Pilot Placebo-controlled Randomized Double-blind Trial of Melatonin in Outpatients With COVID-19 Infection

COVID-19

* Drug: Melatonin * Drug: Placebo

Inclusion Criteria:~Male or non-pregnant female adult ≥18 years of age at time of enrollment.~Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study.~Positive testing for COVID-19 infection by standard RT-PCR assay or equivalent test.~Meets criteria for mild or moderate COVID-19 disease~Subject provides written informed consent prior to initiation of any study procedures.~Understands and agrees to comply with planned study procedures.~Agrees to the collection and storage of saliva samples per protocol.~Subject can provide an emergency contact who the study team can contact in case the subject is not reachable on any of the study visits.~Exclusion Criteria:~Severe (eGFR<30 ml/min) and moderate (eGFR 30-60 ml/min) chronic kidney disease or requiring dialysis~Severe hepatic insufficiency defined as one or more of the following: Cirrhosis diagnosis, Serum ALT > 3x ULN or Alkaline phosphatase >3x ULN or bilirubin >2x ULN in the absence of Gilbert's or hemolysis, Uncontrolled acute or chronic liver disease (e.g. acute hepatitis A, unstable autoimmune hepatitis)~Pregnancy or breast feeding.~History of a seizure disorder.~Patient is taking Fluvoxamine, Capmatinib, Ciprofloxacin (Systemic), Deferasirox, Givosiran, Methoxsalen (Systemic), Mexiletine, Rucaparib, Stiripentol, Thiabendazole, Vemurafenib, Methoxsalen, Sodium oxybate or Echinacea.~Allergy to the study medication~Currently taking melatonin~Currently taking high dose (>500 mg/day) Vitamin C.~Meets criteria for Severe or Critical COVID-19

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Placebo-controlled randomized double-blind trial Masking: Quadruple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cumulative Incidence of Treatment-Emergent Adverse Events | Evaluate the incidence of serious adverse effects and discontinuation secondary to toxicity through 42 days of follow-up as compared to the control arm as assessed by: Cumulative incidence of serious adverse events (SAEs), Cumulative incidence of Grade 3 and 4 adverse events (AEs), Discontinuation or temporary suspension of the investigational medication (for any reason). | 42 days |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of COVID-19 related hospitalization | Incidence of COVID-19 related hospitalization at 42 days | 42 days | | COVID-19 related symptoms | COVID-19 related symptoms as self-reported and on interview. | 42 days | | Rate of resolution of COVID-19 related symptoms | Change from baseline (day 1) as assessed to days 3, 7, 14, 28 and 42 | up to 42 days | | Mortality | 42-day mortality | 42 days |

Melatonin, COVID-19, outpatient, SARS-CoV-2

Melatonin, Antioxidants, Molecular Mechanisms of Pharmacological Action, Protective Agents, Physiological Effects of Drugs, Central Nervous System Depressants

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: Placebo<br>Placebo capsules will be prepared using hypromellose capsules, filled using microcrystalline cellulose. This is the same excipient used in the preparation of the interventional drug. Placebo will be administered orally three times a day for 14 days in the same regimen used for the intervention. | Drug: Placebo<br>* Placebo capsules will be prepared using hypromellose capsules, filled using microcrystalline cellulose. This is the same excipient used in the preparation of the interventional drug. Placebo will be administered orally three times a day for 14 days in the same regimen used for the intervention.<br>* Other names: Microcrystalline Cellulose;| | Experimental: Melatonin 3 mg<br>Melatonin capsules will be prepared using hypromellose capsules containing 3 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days. | Drug: Melatonin<br>* Melatonin capsules will be prepared using hypromellose capsules containing 3 mg or 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days.<br>* Other names: 5-methoxy-N-acetyl tryptamine;| | Experimental: Melatonin 30 mg<br>Melatonin capsules will be prepared using hypromellose capsules containing 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days. | Drug: Melatonin<br>* Melatonin capsules will be prepared using hypromellose capsules containing 3 mg or 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days.<br>* Other names: 5-methoxy-N-acetyl tryptamine;|

Dose-Ranging Study to Assess the Safety and Efficacy of Melatonin in Outpatients Infected With COVID-19 Study Overview ================= Brief Summary ----------------- A pilot placebo-controlled randomized double-blind trial of Melatonin in outpatients with COVID-19 infection to evaluate Safety, Efficacy and Dose-ranging. Detailed Description ----------------- Studies have shown in the blood of patients with COVID-19 there was a marked increase in the cytokines and chemokines interleukin 1β (IL-1β), interferon-γ (IFN-γ), interferon-inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1) and interleukin-4 (IL-4). Consequently, treatments that reduce cytokine/chemokine production that result in a less severe course of disease could be potentially beneficial. Melatonin, a pineal hormone, has been shown to have anti-inflammation, anti-oxidation and immune enhancing features. In multiple animal models of lung injury, Melatonin supplementation has been shown to decrease the number of inflammatory cells, reduce the levels of the cytokines IL-4, IL-5, IL-13 and TNF-a and reduce nitric oxide and hydroxyl radical concentrations. We propose a dose ranging pilot study to assess the safety and efficacy of melatonin in reducing hospitalization in COVID-19 patients with mild-moderate disease. A total of 50 participants will be randomized to the intervention arm (melatonin: 3 mg, or 30 mg three times a day for 14 days) or control arm (placebo) in a 2:2:1 fashion using a permuted block randomization scheme. Analyses will be performed with a focus on estimation of specific clinically important parameters, including safety and preliminary evidence of activity, for planning of a subsequent definitive comparative trial designed to fully assess efficacy. Official Title ----------------- A Pilot Placebo-controlled Randomized Double-blind Trial of Melatonin in Outpatients With COVID-19 Infection Conditions ----------------- COVID-19 Intervention / Treatment ----------------- * Drug: Melatonin * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male or non-pregnant female adult ≥18 years of age at time of enrollment. Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study. Positive testing for COVID-19 infection by standard RT-PCR assay or equivalent test. Meets criteria for mild or moderate COVID-19 disease Subject provides written informed consent prior to initiation of any study procedures. Understands and agrees to comply with planned study procedures. Agrees to the collection and storage of saliva samples per protocol. Subject can provide an emergency contact who the study team can contact in case the subject is not reachable on any of the study visits. Exclusion Criteria: Severe (eGFR<30 ml/min) and moderate (eGFR 30-60 ml/min) chronic kidney disease or requiring dialysis Severe hepatic insufficiency defined as one or more of the following: Cirrhosis diagnosis, Serum ALT > 3x ULN or Alkaline phosphatase >3x ULN or bilirubin >2x ULN in the absence of Gilbert's or hemolysis, Uncontrolled acute or chronic liver disease (e.g. acute hepatitis A, unstable autoimmune hepatitis) Pregnancy or breast feeding. History of a seizure disorder. Patient is taking Fluvoxamine, Capmatinib, Ciprofloxacin (Systemic), Deferasirox, Givosiran, Methoxsalen (Systemic), Mexiletine, Rucaparib, Stiripentol, Thiabendazole, Vemurafenib, Methoxsalen, Sodium oxybate or Echinacea. Allergy to the study medication Currently taking melatonin Currently taking high dose (>500 mg/day) Vitamin C. Meets criteria for Severe or Critical COVID-19 Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Placebo-controlled randomized double-blind trial Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: Placebo<br>Placebo capsules will be prepared using hypromellose capsules, filled using microcrystalline cellulose. This is the same excipient used in the preparation of the interventional drug. Placebo will be administered orally three times a day for 14 days in the same regimen used for the intervention. | Drug: Placebo<br>* Placebo capsules will be prepared using hypromellose capsules, filled using microcrystalline cellulose. This is the same excipient used in the preparation of the interventional drug. Placebo will be administered orally three times a day for 14 days in the same regimen used for the intervention.<br>* Other names: Microcrystalline Cellulose;| | Experimental: Melatonin 3 mg<br>Melatonin capsules will be prepared using hypromellose capsules containing 3 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days. | Drug: Melatonin<br>* Melatonin capsules will be prepared using hypromellose capsules containing 3 mg or 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days.<br>* Other names: 5-methoxy-N-acetyl tryptamine;| | Experimental: Melatonin 30 mg<br>Melatonin capsules will be prepared using hypromellose capsules containing 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days. | Drug: Melatonin<br>* Melatonin capsules will be prepared using hypromellose capsules containing 3 mg or 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days.<br>* Other names: 5-methoxy-N-acetyl tryptamine;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cumulative Incidence of Treatment-Emergent Adverse Events | Evaluate the incidence of serious adverse effects and discontinuation secondary to toxicity through 42 days of follow-up as compared to the control arm as assessed by: Cumulative incidence of serious adverse events (SAEs), Cumulative incidence of Grade 3 and 4 adverse events (AEs), Discontinuation or temporary suspension of the investigational medication (for any reason). | 42 days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of COVID-19 related hospitalization | Incidence of COVID-19 related hospitalization at 42 days | 42 days | | COVID-19 related symptoms | COVID-19 related symptoms as self-reported and on interview. | 42 days | | Rate of resolution of COVID-19 related symptoms | Change from baseline (day 1) as assessed to days 3, 7, 14, 28 and 42 | up to 42 days | | Mortality | 42-day mortality | 42 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Melatonin, COVID-19, outpatient, SARS-CoV-2

NCT01243372

Biomarkers in Predicting Response to Cetuximab in Patients With Advanced Colorectal Cancer

RATIONALE: Studying samples of tissue in the laboratory from patients who received cetuximab may help doctors understand and predict how well patients will respond to treatment.~PURPOSE: This research study is studying biomarkers in predicting response to cetuximab in patients with advanced colorectal cancer.

OBJECTIVES:~Primary~To determine, among patients with advanced CRC, whether the effect of treatment (cetuximab vs bevacizumab) on progression-free survival (PFS) depends on tumor BRAF V600E mutational status.~Secondary~To study the relationships between tumor BRAF V600E mutational status, OS, and tumor response.~OUTLINE: This is a multicenter study.~Previously collected formalin-fixed and paraffin-embedded baseline tumor samples are analyzed for BRAF V600E mutation. Mutation status is correlated with clinical response and outcome data from patients enrolled on CALGB-C80405.

Evaluating BRAF Mutations as Predictors of Efficacy in Cetuximab-Treated Colorectal Cancer Patients: A Retrospective Study of Tissues From CALGB / SWOG

Colorectal Cancer

* Genetic: mutation analysis * Other: laboratory biomarker analysis

DISEASE CHARACTERISTICS:~Participation in CALGB-C80405~Have KRAS WT or KRAS mut tumor~Randomized to treatment with either bevacizumab or cetuximab alone~Patients randomized to the combination therapy are not eligible~Available specimens at the PCO for BRAF mutation detection~Patient consent for use of samples

18 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Progression-free survival as measured by RECIST | | Up to 36 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | overall survival | | Up to 36 months | | tumor response as measured by RECIST | | Up to 36 months |

recurrent colon cancer, stage IIIA colon cancer, stage IIIB colon cancer, stage IIIC colon cancer, stage IVA colon cancer, stage IVB colon cancer, recurrent rectal cancer, stage III rectal cancer, stage IV rectal cancer

Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Correlative (BRAF V600E mutation analysis)<br>Previously collected formalin-fixed and paraffin-embedded baseline tumor samples are analyzed for BRAF V600E mutation. Mutation status is correlated with clinical response and outcome data from patients enrolled on CALGB-C80405. | Genetic: mutation analysis<br> <br> Other: laboratory biomarker analysis<br> <br> |

Biomarkers in Predicting Response to Cetuximab in Patients With Advanced Colorectal Cancer Study Overview ================= Brief Summary ----------------- RATIONALE: Studying samples of tissue in the laboratory from patients who received cetuximab may help doctors understand and predict how well patients will respond to treatment. PURPOSE: This research study is studying biomarkers in predicting response to cetuximab in patients with advanced colorectal cancer. Detailed Description ----------------- OBJECTIVES: Primary To determine, among patients with advanced CRC, whether the effect of treatment (cetuximab vs bevacizumab) on progression-free survival (PFS) depends on tumor BRAF V600E mutational status. Secondary To study the relationships between tumor BRAF V600E mutational status, OS, and tumor response. OUTLINE: This is a multicenter study. Previously collected formalin-fixed and paraffin-embedded baseline tumor samples are analyzed for BRAF V600E mutation. Mutation status is correlated with clinical response and outcome data from patients enrolled on CALGB-C80405. Official Title ----------------- Evaluating BRAF Mutations as Predictors of Efficacy in Cetuximab-Treated Colorectal Cancer Patients: A Retrospective Study of Tissues From CALGB / SWOG Conditions ----------------- Colorectal Cancer Intervention / Treatment ----------------- * Genetic: mutation analysis * Other: laboratory biomarker analysis Participation Criteria ================= Eligibility Criteria ----------------- DISEASE CHARACTERISTICS: Participation in CALGB-C80405 Have KRAS WT or KRAS mut tumor Randomized to treatment with either bevacizumab or cetuximab alone Patients randomized to the combination therapy are not eligible Available specimens at the PCO for BRAF mutation detection Patient consent for use of samples Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Correlative (BRAF V600E mutation analysis)<br>Previously collected formalin-fixed and paraffin-embedded baseline tumor samples are analyzed for BRAF V600E mutation. Mutation status is correlated with clinical response and outcome data from patients enrolled on CALGB-C80405. | Genetic: mutation analysis<br> <br> Other: laboratory biomarker analysis<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Progression-free survival as measured by RECIST | | Up to 36 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | overall survival | | Up to 36 months | | tumor response as measured by RECIST | | Up to 36 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- recurrent colon cancer, stage IIIA colon cancer, stage IIIB colon cancer, stage IIIC colon cancer, stage IVA colon cancer, stage IVB colon cancer, recurrent rectal cancer, stage III rectal cancer, stage IV rectal cancer

NCT05372276

Comparison of Mental Skills of Professional Esports Players With Different Levels of Physical Activity

Competitive video games, defined as esports, have been increasing in popularity especially in the last ten years.~In this study, our primary aim is; to compare the mental abilities of professional esport players with different physical activity levels.

Competitive video games, defined as esports, have been increasing in popularity especially in the last ten years.~In this study, our primary aim is; to compare the mental abilities of professional esport players with different physical activity levels.~The second aim of our study is; to reveal information about the physical activity levels of Turkish professional esports players. In addition, pioneering information will be presented to both clinicians and researchers on physical activity in esports, which is frequently discussed today.

A Comparison of Mental Toughness and Mental Imagination Skills of Professional Esports Players With Different Levels of Physical Activity

Healthy, Physical Inactivity

* Other: Assessment 1 * Other: Assessment 2 * Other: Assessment 3 * Other: Assessment 4

Inclusion Criteria:~Beingover 18 years old~Being a professional esports player~Being contracted with an esports club~Esports branch includes games played on a computer platform, in sitting position, using mouse, keyboard and monitor.~Volunteering for the study~Exclusion Criteria:~Sports branches in which different equipments that can change biomechanical properties such as phone, console, joystick are used.~Having less than 2 years of esports background~Having any musculoskeletal injury within 6 months~Having any neurological, rheumatological, cardiac problems~Having a psychiatric illness~Having any communication problems

18 Years

All

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The International Physical Activity Questionnaires (IPAQ) | The short form of the International Physical Activity Questionnaire (UFAA) will be used to determine the physical activity levels of the participants. The UFAA-Short Form is a valid tool used to assess physical activity in young adults. It is a 7-item scale that evaluates the duration and frequency of vigorous physical activity, moderate physical activity, walking and sedentary behavior based on MET values. Physical activity levels are classified into 3 categories according to the scores obtained by multiplying the duration, frequency and MET values of the physical activities that the participants participated in within 7 days and for at least 10 minutes. Accordingly, <600 MET - min/week is defined as inactive, 600 - 3000 MET - min/week low, and >3000 MET - min/week is defined as sufficient physical activity level. | 3 months, July 2022 - September 2022 |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Mental Toughness Questionnaire in Sports | The mental toughness parameters of the participants will be evaluated face-to-face with the Mental Toughness Questionnaire in Sports. It was developed by Sheard, Golby and Van Wersch in 2009. It is a 14-item scale that includes three sub-dimensions of trust, continuity and control and provides information about mental resilience in young adults. Although there are reverse questions in the scale, it includes a Likert-type evaluation between 1 and 4 (1= Completely false, 4= Completely true). Although the highest score that can be obtained is 56, high scores from the scale show that the athletes have a high level of mental endurance. | 4 months, September 2022 - December 2022 | | Sport Imagery Questionaire | The imagination skills of the participants will be evaluated face-to-face with the Sports Imagery Questionnaire. It is a 30-item scale developed by Hall, Mack, Paivio, and Hausenblas in 1998, including 5 sub-dimensions. Each item included in the scale is scored between 1 and 7 by the athletes. Although the highest score that can be obtained is 210, high scores indicate an increase in visualization skills. | 4 months, September 2022 - December 2022 |

esport, physical activity, mental toughness, mental imaginery

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Inactive<br>The score obtained by multiplying the duration, frequency and MET values of the physical activities in which the participants participated in 7 days and for at least 10 minutes is <600 MET - min/week.~After the participants are divided into groups according to their physical activity levels, mental toughness and mental imagery skills will be evaluated with the Mental Toughness Scale and the Sports Imagery Questionnaire. | Other: Assessment 1<br>* Mental Toughness Questionnaire in Sport<br>Other: Assessment 2<br>* Sport Imagery Questionnaire<br>Other: Assessment 3<br>* The Pittsburgh Sleep Quality Index<br>Other: Assessment 4<br>* The Perceived Stress Scale (PSS)<br>| | Low Level Physical Activity (PA)<br>The score obtained by multiplying the duration, frequency and MET values of the physical activities in which the participants participated in 7 days and for at least 10 minutes is 600 - 3000 MET - min/week.~After the participants are divided into groups according to their physical activity levels, mental toughness and mental imagery skills will be evaluated with the Mental Toughness Scale and the Sports Imagery Questionnaire. | Other: Assessment 1<br>* Mental Toughness Questionnaire in Sport<br>Other: Assessment 2<br>* Sport Imagery Questionnaire<br>Other: Assessment 3<br>* The Pittsburgh Sleep Quality Index<br>Other: Assessment 4<br>* The Perceived Stress Scale (PSS)<br>| | Adequate Level Physical Activity (PA)<br>The score obtained by multiplying the duration, frequency and MET values of the physical activities in which the participants participated in 7 days and for at least 10 minutes is >3000 MET - min/week.~After the participants are divided into groups according to their physical activity levels, mental toughness and mental imagery skills will be evaluated with the Mental Toughness Scale and the Sports Imagery Questionnaire. | Other: Assessment 1<br>* Mental Toughness Questionnaire in Sport<br>Other: Assessment 2<br>* Sport Imagery Questionnaire<br>Other: Assessment 3<br>* The Pittsburgh Sleep Quality Index<br>Other: Assessment 4<br>* The Perceived Stress Scale (PSS)<br>|

Comparison of Mental Skills of Professional Esports Players With Different Levels of Physical Activity Study Overview ================= Brief Summary ----------------- Competitive video games, defined as esports, have been increasing in popularity especially in the last ten years. In this study, our primary aim is; to compare the mental abilities of professional esport players with different physical activity levels. Detailed Description ----------------- Competitive video games, defined as esports, have been increasing in popularity especially in the last ten years. In this study, our primary aim is; to compare the mental abilities of professional esport players with different physical activity levels. The second aim of our study is; to reveal information about the physical activity levels of Turkish professional esports players. In addition, pioneering information will be presented to both clinicians and researchers on physical activity in esports, which is frequently discussed today. Official Title ----------------- A Comparison of Mental Toughness and Mental Imagination Skills of Professional Esports Players With Different Levels of Physical Activity Conditions ----------------- Healthy, Physical Inactivity Intervention / Treatment ----------------- * Other: Assessment 1 * Other: Assessment 2 * Other: Assessment 3 * Other: Assessment 4 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Beingover 18 years old Being a professional esports player Being contracted with an esports club Esports branch includes games played on a computer platform, in sitting position, using mouse, keyboard and monitor. Volunteering for the study Exclusion Criteria: Sports branches in which different equipments that can change biomechanical properties such as phone, console, joystick are used. Having less than 2 years of esports background Having any musculoskeletal injury within 6 months Having any neurological, rheumatological, cardiac problems Having a psychiatric illness Having any communication problems Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Inactive<br>The score obtained by multiplying the duration, frequency and MET values of the physical activities in which the participants participated in 7 days and for at least 10 minutes is <600 MET - min/week. After the participants are divided into groups according to their physical activity levels, mental toughness and mental imagery skills will be evaluated with the Mental Toughness Scale and the Sports Imagery Questionnaire. | Other: Assessment 1<br>* Mental Toughness Questionnaire in Sport<br>Other: Assessment 2<br>* Sport Imagery Questionnaire<br>Other: Assessment 3<br>* The Pittsburgh Sleep Quality Index<br>Other: Assessment 4<br>* The Perceived Stress Scale (PSS)<br>| | Low Level Physical Activity (PA)<br>The score obtained by multiplying the duration, frequency and MET values of the physical activities in which the participants participated in 7 days and for at least 10 minutes is 600 - 3000 MET - min/week. After the participants are divided into groups according to their physical activity levels, mental toughness and mental imagery skills will be evaluated with the Mental Toughness Scale and the Sports Imagery Questionnaire. | Other: Assessment 1<br>* Mental Toughness Questionnaire in Sport<br>Other: Assessment 2<br>* Sport Imagery Questionnaire<br>Other: Assessment 3<br>* The Pittsburgh Sleep Quality Index<br>Other: Assessment 4<br>* The Perceived Stress Scale (PSS)<br>| | Adequate Level Physical Activity (PA)<br>The score obtained by multiplying the duration, frequency and MET values of the physical activities in which the participants participated in 7 days and for at least 10 minutes is >3000 MET - min/week. After the participants are divided into groups according to their physical activity levels, mental toughness and mental imagery skills will be evaluated with the Mental Toughness Scale and the Sports Imagery Questionnaire. | Other: Assessment 1<br>* Mental Toughness Questionnaire in Sport<br>Other: Assessment 2<br>* Sport Imagery Questionnaire<br>Other: Assessment 3<br>* The Pittsburgh Sleep Quality Index<br>Other: Assessment 4<br>* The Perceived Stress Scale (PSS)<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The International Physical Activity Questionnaires (IPAQ) | The short form of the International Physical Activity Questionnaire (UFAA) will be used to determine the physical activity levels of the participants. The UFAA-Short Form is a valid tool used to assess physical activity in young adults. It is a 7-item scale that evaluates the duration and frequency of vigorous physical activity, moderate physical activity, walking and sedentary behavior based on MET values. Physical activity levels are classified into 3 categories according to the scores obtained by multiplying the duration, frequency and MET values of the physical activities that the participants participated in within 7 days and for at least 10 minutes. Accordingly, <600 MET - min/week is defined as inactive, 600 - 3000 MET - min/week low, and >3000 MET - min/week is defined as sufficient physical activity level. | 3 months, July 2022 - September 2022 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Mental Toughness Questionnaire in Sports | The mental toughness parameters of the participants will be evaluated face-to-face with the Mental Toughness Questionnaire in Sports. It was developed by Sheard, Golby and Van Wersch in 2009. It is a 14-item scale that includes three sub-dimensions of trust, continuity and control and provides information about mental resilience in young adults. Although there are reverse questions in the scale, it includes a Likert-type evaluation between 1 and 4 (1= Completely false, 4= Completely true). Although the highest score that can be obtained is 56, high scores from the scale show that the athletes have a high level of mental endurance. | 4 months, September 2022 - December 2022 | | Sport Imagery Questionaire | The imagination skills of the participants will be evaluated face-to-face with the Sports Imagery Questionnaire. It is a 30-item scale developed by Hall, Mack, Paivio, and Hausenblas in 1998, including 5 sub-dimensions. Each item included in the scale is scored between 1 and 7 by the athletes. Although the highest score that can be obtained is 210, high scores indicate an increase in visualization skills. | 4 months, September 2022 - December 2022 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- esport, physical activity, mental toughness, mental imaginery

NCT01763073

Beliefs and Practice Intentions of Future Ob/Gyn Residents Regarding Reproductive Healthcare

The objective of this study is to ascertain factors shaping medical students' pre-residency intention to provide abortion through an in-depth qualitative investigation into the context and experiences that shape intention to provide.

Beliefs and Practice Intentions of Future Ob/Gyn Residents Regarding Reproductive Healthcare

Focus: Pre-residency Intention to Provide Abortion

Inclusion Criteria:~current 4th-year medical student~US accredited medical school~has applied to, but not yet been accepted into, obstetrics and gynecology residency programs~Exclusion Criteria:~age less than 18 years~former student reapplying to residency (e.g., not current 4th-year student)~has not yet applied to residency~has already been accepted to residency

18 Years

All

Accepts Healthy Volunteers

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Factors affecting pre-residency intention to provide abortion | Factors will be identified by systematically coding qualitative data using a combination of deductive and inductive analytical strategies. | Up to 15 months. Each participant will be interviewed once, between January and March 2013 or between September 2013 through March 2014. |

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Medical Students<br>Fourth-year students in accredited US medical schools who have applied to, but not yet been matched with, residency programs in obstetrics and gynecology. | |

Beliefs and Practice Intentions of Future Ob/Gyn Residents Regarding Reproductive Healthcare Study Overview ================= Brief Summary ----------------- The objective of this study is to ascertain factors shaping medical students' pre-residency intention to provide abortion through an in-depth qualitative investigation into the context and experiences that shape intention to provide. Official Title ----------------- Beliefs and Practice Intentions of Future Ob/Gyn Residents Regarding Reproductive Healthcare Conditions ----------------- Focus: Pre-residency Intention to Provide Abortion Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: current 4th-year medical student US accredited medical school has applied to, but not yet been accepted into, obstetrics and gynecology residency programs Exclusion Criteria: age less than 18 years former student reapplying to residency (e.g., not current 4th-year student) has not yet applied to residency has already been accepted to residency Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Medical Students<br>Fourth-year students in accredited US medical schools who have applied to, but not yet been matched with, residency programs in obstetrics and gynecology. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Factors affecting pre-residency intention to provide abortion | Factors will be identified by systematically coding qualitative data using a combination of deductive and inductive analytical strategies. | Up to 15 months. Each participant will be interviewed once, between January and March 2013 or between September 2013 through March 2014. |

NCT00970840

Acceptability of Lipid-Based Nutrient Supplements (LNS) for Women and Infants

Inadequate micronutrient intakes during pregnancy, lactation and infancy remain a major problem in Ghana. Lipid-based nutrient supplements (LNS) made using vegetable oil, groundnut paste, milk, sugar, and micronutrients may offer a solution.~The proposed study will test the acceptability of a lipid-based nutrient supplement designed for infants (LNS-20gM) and another designed for pregnant and lactating women (LNS-P&L). Participants will consume a test meal consisting of LNS-20gM (20 infants) or LNS-P&L (20 pregnant and lactating women) mixed with fermented maize porridge, after which they will be given the respective LNS supplement for use at home for 14 d. Primary outcome is the proportion of the test-meal consumed. The investigators hypothesize that subjects will consume at 75% of the test meal offered.

This study is a taste test to confirm the acceptability of lipid-based nutrient supplements (LNS), which are semi-solid pastes comprising groundnut paste, milk, sugar, vegetable oil and micronutrients, for home fortification of foods consumed by infants and by pregnant and lactating women. Two types of supplements will be evaluated, one for infants (LNS20gM) and one for pregnant and lactating women (LNS P&L). The LNS-20gM is similar to the Nutributter we used previously in Ghana and provides generally the Recommended Nutrient Intakes (RNI) for 18 vitamins and minerals for infants from 6 to 18 mo of age. The LNS-P&L is modeled on the UNICEF/WHO/UNU international multiple micronutrient preparation (UNIMMAP) for pregnant and lactating women and similar products used in Guinea Bissau. Each supplement (20 g/day) will provide 118 kcal/day.~Procedures:The study will be carried out in two phases. The first test trial will be conducted within the premises of the Maternal and Child Health Clinics, where study participants will be recruited.~Potential study participants or their mothers (in the case of infants) will be asked verbally using a screening questionnaire at the time of recruitment if they are known to be intolerant to peanut or milk products, in which case they will be excluded. Because infants must have been receiving complementary foods at least 30 days prior to taking part in the study, this will not be too difficult to find out. For subjects unaware of whether they are intolerant to peanut or milk products, they will be asked not to go home immediately after finishing the experiment, but to continue to remain in (or around) the testing room for at least one hour whilst the study staff keep watch. Should there be any skin, respiratory or gastrointestinal symptoms in any subject during that time, they will be immediately referred to the hospital. When leaving the testing room for the home, those subjects (or their mothers) will be given the project's mobile phone number to call in case there are any symptoms during the next few hours.~Potential subjects or their mothers (in the case of infants) will be asked if they feel ill using the screening questionnaire. Subjects who report any feeling of illness will be excluded. The Maternal and Child Health clinics (MCH) where subjects will be recruited provide mainly routine services for women (such as ante-natal services for pregnant women) and children (such as weight monitoring and promotion and vaccination). We expect that nearly all women and infants attending these clinics will be apparently in good health and not ill.~Phase 1 - Test-feeding:~Study participants will be women (n = 20) ≥ 18 y of age who are either pregnant (n = 10) or lactating (n = 10) and infants (n = 20 accompanied by their mothers) 6 - 12 mo of age randomly-selected from Maternal and Child Health clinics in Manya and Yiko Krobo districts of the Eastern Region of Ghana. All subjects must be apparently healthy and must not have eaten any food (including breast milk) during the previous one hour.~Test-feeding of LNS P&L:~After consent, pregnant (n=10) and lactating women (n=10) will be asked to come to the clinic the next day for an orientation session during which background data will be collected and the experimental procedures will be practiced including tasting of the food and completion of the tasting questionnaire. The second day will be Test Day 1, during which the actual tasting will be recorded. Women will be asked to consume 45 g of koko mixed with LNS P&L (prepared from mixing 150 g LNS-P&L with 600 g fresh koko with moisture content of about 90%). Time taken to consume the entire amount, or proportion of the amount consumed within 15 minutes, will be measured. Women will be asked to rate the mixture's appearance, aroma, flavor, consistency and overall degree of liking using a hedonic scale. On the third day (Test Day 2) of the trial, the above procedures will be repeated using koko mixed with Nutributter instead.~Koko for the test feeding will be provided by the project. Project staff will purchase fermented dough (the main ingredient) from the local market to prepare the koko under good hygienic conditions in our project house. After preparation, the koko will be kept hot in a thermos flask prior to being served to study participants at the MCH clinic. Between the time the koko is prepared and the time the test feeding is completed, which will take 2-3 hours, the koko can be kept at a temperature of 70 - 90 °C inside the thermos flask to prevent bacterial contamination. The Nutributter and the LNS supplements will be commercially produced by Nutriset SAS (Malaunay, France) and provided to the Project for testing.~Test-feeding of LNS20gM:~After consent, the mother (or care-taker) of each participating infant will be asked to come to the clinic with the child the next day for an orientation session during which background data will be collected and the experimental procedures will be practiced including tasting of the food and completion of the tasting questionnaire. The second day will be Test Day 1, during which the actual tasting will be recorded. Mothers or caretakers will be given 50 g of koko mixed with LNS 20gM (prepared from mixing 150 g LNS-20gM with 600 g fresh koko with moisture content of about 90%). They will be asked to consume one teaspoon of the mixture (~ 5 g), and then feed the rest (~ 45 g) to their infants after it is re-weighed. During this time, the child should be awake and alert, and either calm or fussy - but not drowsy or crying. Time taken by the child to consume the remaining portion, or proportion consumed by the child within 15 minutes, will be measured. The mother or caretaker will then rate the mixture's appearance, aroma, flavor and consistency based on her own opinion, and her perception of the infant's degree of liking. Mothers will be asked to report to us if the child vomits in the next hour, or develops any new symptoms such as rash or wheezing. On the third day (Test Day 2) of the trial, the above procedures will be repeated using koko mixed with Nutributter instead.~Phase 2 - Assessment under real-life conditions:~Pregnant and lactating women who participated in the Phase 1 trial will be given a two-week supply of LNS P&L, which they will add to their prepared food daily during the two-week period. Mothers of children who participated in the Phase 1 trial will receive LNS20gM, which they will add to their infants' prepared food for 2 weeks. The dose for LNS P&L or LNS20gM is 20 g/day. To ensure that subjects consume the entire daily dose, women will be instructed, as done previously in our study in Ghana, to mix their own or their infant's daily dose with 2-3 tablespoons of the food, to be consumed before consuming the rest of the food.~Dosage and directions for use will be as follows: 20 g (~4 teaspoons) per day divided into 2 portions and consumed at two different times of the day (2 x 2 teaspoons). Mix the portion of the supplement to be consumed with 2-3 tablespoons of the already prepared food, and eat the mixture before eating the rest of the food. Do not cook food with the supplement. Store supplement at room temperature. There is no need for refrigeration.~A structured questionnaire will be used to gather background information on socioeconomic status, and maternal and infant feeding behavior. The amount of LNS consumed by subjects will be monitored weekly, and the reactions to the products will be obtained at the end.

Acceptability of Lipid-based Nutrient Supplements (LNS) for Women and Infants

Anemia, Malnutrition

* Dietary Supplement: LNS-20gM or LNS-P&L

Inclusion Criteria (infants):~6-12 months of age~currently receiving breast milk~has been consuming complementary foods for at least 30 days~Inclusion Criteria (women):~being ≥ 18 years of age~confirmed to be pregnant or breastfeeding~Exclusion Criteria:~intolerance to milk or peanut~illness requiring referral

6 Months

All

Accepts Healthy Volunteers

Primary Purpose: Other Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of test-meal consumed | | One day |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Degree of liking for appearance, aroma, flavor and consistency of LNS product mixed with koko | | 14 days | | Amount of LNS consumed during the 14-day study period | | 14 days |

Acceptability, Supplements, Home-fortification

Malnutrition, Nutrition Disorders

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: LNS-20gM or LNS-P&L<br> | Dietary Supplement: LNS-20gM or LNS-P&L<br>* Participants consumed a test meal (45 g or 50 g) consisting of LNS-20gM or LNS-P&L mixed with fermented maize porridge, after which they were provided with the respective LNS supplements for use at home daily for 14 d<br>|

Acceptability of Lipid-Based Nutrient Supplements (LNS) for Women and Infants Study Overview ================= Brief Summary ----------------- Inadequate micronutrient intakes during pregnancy, lactation and infancy remain a major problem in Ghana. Lipid-based nutrient supplements (LNS) made using vegetable oil, groundnut paste, milk, sugar, and micronutrients may offer a solution. The proposed study will test the acceptability of a lipid-based nutrient supplement designed for infants (LNS-20gM) and another designed for pregnant and lactating women (LNS-P&L). Participants will consume a test meal consisting of LNS-20gM (20 infants) or LNS-P&L (20 pregnant and lactating women) mixed with fermented maize porridge, after which they will be given the respective LNS supplement for use at home for 14 d. Primary outcome is the proportion of the test-meal consumed. The investigators hypothesize that subjects will consume at 75% of the test meal offered. Detailed Description ----------------- This study is a taste test to confirm the acceptability of lipid-based nutrient supplements (LNS), which are semi-solid pastes comprising groundnut paste, milk, sugar, vegetable oil and micronutrients, for home fortification of foods consumed by infants and by pregnant and lactating women. Two types of supplements will be evaluated, one for infants (LNS20gM) and one for pregnant and lactating women (LNS P&L). The LNS-20gM is similar to the Nutributter we used previously in Ghana and provides generally the Recommended Nutrient Intakes (RNI) for 18 vitamins and minerals for infants from 6 to 18 mo of age. The LNS-P&L is modeled on the UNICEF/WHO/UNU international multiple micronutrient preparation (UNIMMAP) for pregnant and lactating women and similar products used in Guinea Bissau. Each supplement (20 g/day) will provide 118 kcal/day. Procedures:The study will be carried out in two phases. The first test trial will be conducted within the premises of the Maternal and Child Health Clinics, where study participants will be recruited. Potential study participants or their mothers (in the case of infants) will be asked verbally using a screening questionnaire at the time of recruitment if they are known to be intolerant to peanut or milk products, in which case they will be excluded. Because infants must have been receiving complementary foods at least 30 days prior to taking part in the study, this will not be too difficult to find out. For subjects unaware of whether they are intolerant to peanut or milk products, they will be asked not to go home immediately after finishing the experiment, but to continue to remain in (or around) the testing room for at least one hour whilst the study staff keep watch. Should there be any skin, respiratory or gastrointestinal symptoms in any subject during that time, they will be immediately referred to the hospital. When leaving the testing room for the home, those subjects (or their mothers) will be given the project's mobile phone number to call in case there are any symptoms during the next few hours. Potential subjects or their mothers (in the case of infants) will be asked if they feel ill using the screening questionnaire. Subjects who report any feeling of illness will be excluded. The Maternal and Child Health clinics (MCH) where subjects will be recruited provide mainly routine services for women (such as ante-natal services for pregnant women) and children (such as weight monitoring and promotion and vaccination). We expect that nearly all women and infants attending these clinics will be apparently in good health and not ill. Phase 1 - Test-feeding: Study participants will be women (n = 20) ≥ 18 y of age who are either pregnant (n = 10) or lactating (n = 10) and infants (n = 20 accompanied by their mothers) 6 - 12 mo of age randomly-selected from Maternal and Child Health clinics in Manya and Yiko Krobo districts of the Eastern Region of Ghana. All subjects must be apparently healthy and must not have eaten any food (including breast milk) during the previous one hour. Test-feeding of LNS P&L: After consent, pregnant (n=10) and lactating women (n=10) will be asked to come to the clinic the next day for an orientation session during which background data will be collected and the experimental procedures will be practiced including tasting of the food and completion of the tasting questionnaire. The second day will be Test Day 1, during which the actual tasting will be recorded. Women will be asked to consume 45 g of koko mixed with LNS P&L (prepared from mixing 150 g LNS-P&L with 600 g fresh koko with moisture content of about 90%). Time taken to consume the entire amount, or proportion of the amount consumed within 15 minutes, will be measured. Women will be asked to rate the mixture's appearance, aroma, flavor, consistency and overall degree of liking using a hedonic scale. On the third day (Test Day 2) of the trial, the above procedures will be repeated using koko mixed with Nutributter instead. Koko for the test feeding will be provided by the project. Project staff will purchase fermented dough (the main ingredient) from the local market to prepare the koko under good hygienic conditions in our project house. After preparation, the koko will be kept hot in a thermos flask prior to being served to study participants at the MCH clinic. Between the time the koko is prepared and the time the test feeding is completed, which will take 2-3 hours, the koko can be kept at a temperature of 70 - 90 °C inside the thermos flask to prevent bacterial contamination. The Nutributter and the LNS supplements will be commercially produced by Nutriset SAS (Malaunay, France) and provided to the Project for testing. Test-feeding of LNS20gM: After consent, the mother (or care-taker) of each participating infant will be asked to come to the clinic with the child the next day for an orientation session during which background data will be collected and the experimental procedures will be practiced including tasting of the food and completion of the tasting questionnaire. The second day will be Test Day 1, during which the actual tasting will be recorded. Mothers or caretakers will be given 50 g of koko mixed with LNS 20gM (prepared from mixing 150 g LNS-20gM with 600 g fresh koko with moisture content of about 90%). They will be asked to consume one teaspoon of the mixture ( 5 g), and then feed the rest ( 45 g) to their infants after it is re-weighed. During this time, the child should be awake and alert, and either calm or fussy - but not drowsy or crying. Time taken by the child to consume the remaining portion, or proportion consumed by the child within 15 minutes, will be measured. The mother or caretaker will then rate the mixture's appearance, aroma, flavor and consistency based on her own opinion, and her perception of the infant's degree of liking. Mothers will be asked to report to us if the child vomits in the next hour, or develops any new symptoms such as rash or wheezing. On the third day (Test Day 2) of the trial, the above procedures will be repeated using koko mixed with Nutributter instead. Phase 2 - Assessment under real-life conditions: Pregnant and lactating women who participated in the Phase 1 trial will be given a two-week supply of LNS P&L, which they will add to their prepared food daily during the two-week period. Mothers of children who participated in the Phase 1 trial will receive LNS20gM, which they will add to their infants' prepared food for 2 weeks. The dose for LNS P&L or LNS20gM is 20 g/day. To ensure that subjects consume the entire daily dose, women will be instructed, as done previously in our study in Ghana, to mix their own or their infant's daily dose with 2-3 tablespoons of the food, to be consumed before consuming the rest of the food. Dosage and directions for use will be as follows: 20 g ( 4 teaspoons) per day divided into 2 portions and consumed at two different times of the day (2 x 2 teaspoons). Mix the portion of the supplement to be consumed with 2-3 tablespoons of the already prepared food, and eat the mixture before eating the rest of the food. Do not cook food with the supplement. Store supplement at room temperature. There is no need for refrigeration. A structured questionnaire will be used to gather background information on socioeconomic status, and maternal and infant feeding behavior. The amount of LNS consumed by subjects will be monitored weekly, and the reactions to the products will be obtained at the end. Official Title ----------------- Acceptability of Lipid-based Nutrient Supplements (LNS) for Women and Infants Conditions ----------------- Anemia, Malnutrition Intervention / Treatment ----------------- * Dietary Supplement: LNS-20gM or LNS-P&L Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria (infants): 6-12 months of age currently receiving breast milk has been consuming complementary foods for at least 30 days Inclusion Criteria (women): being ≥ 18 years of age confirmed to be pregnant or breastfeeding Exclusion Criteria: intolerance to milk or peanut illness requiring referral Ages Eligible for Study ----------------- Minimum Age: 6 Months Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Other Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: LNS-20gM or LNS-P&L<br> | Dietary Supplement: LNS-20gM or LNS-P&L<br>* Participants consumed a test meal (45 g or 50 g) consisting of LNS-20gM or LNS-P&L mixed with fermented maize porridge, after which they were provided with the respective LNS supplements for use at home daily for 14 d<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of test-meal consumed | | One day | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Degree of liking for appearance, aroma, flavor and consistency of LNS product mixed with koko | | 14 days | | Amount of LNS consumed during the 14-day study period | | 14 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Acceptability, Supplements, Home-fortification

NCT01077661

Regulatory Nebilet PMS

An open label, multi-centre, non-interventional post-marketing surveillance (PMS) to monitor the safety and effectiveness of Nebivolol administered in Korean patients according to the prescribing information

An open label, multi-centre, non-interventional post-marketing surveillance (PMS) to monitor the safety and effectiveness of Nebivolol administered in Korean patients according to the prescribing information~Nebivolol will be administered to Hypertension or Chronic heart failure (CHF) patients as described the prescribing information of Nebivolol by physician's decision.

An Open Label, Multi-centre, Non-interventional Post-marketing Surveillance (PMS) to Monitor the Safety and Effectiveness of Nebilet Administered in Korean Patients According to the Prescribing Information

Hypertension, Heart Failure

* Drug: Nebivolol

All subjects must satisfy the following criteria at PMS entry according to KFDA PMS regulation:~Subjects with indication in the prescribing information~Subjects administrated Nebivolol by physician's decision~Subjects with no contraindication according to the prescribing information

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Occurrence of adverse events after Nebivolol administration | | 3months, 6months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Occurrence of unexpected or serious adverse event after Nebivolol administration and effectiveness of Occurrence of unexpected or serious adverse event after Nebivolol administration and effectiveness of Nebivolol | | 3 months, 6months |

Nebivolol, PMS (post-marketing surveillance)

Nebivolol, Antihypertensive Agents, Vasodilator Agents, Adrenergic beta-1 Receptor Agonists, Adrenergic beta-Agonists, Adrenergic Agonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Patients administrated Nebivolol<br>There is only one group. This group includes patients administrated Nebivolol | Drug: Nebivolol<br>* patients administrated Nebivolol according to the prescribing information<br>|

Regulatory Nebilet PMS Study Overview ================= Brief Summary ----------------- An open label, multi-centre, non-interventional post-marketing surveillance (PMS) to monitor the safety and effectiveness of Nebivolol administered in Korean patients according to the prescribing information Detailed Description ----------------- An open label, multi-centre, non-interventional post-marketing surveillance (PMS) to monitor the safety and effectiveness of Nebivolol administered in Korean patients according to the prescribing information Nebivolol will be administered to Hypertension or Chronic heart failure (CHF) patients as described the prescribing information of Nebivolol by physician's decision. Official Title ----------------- An Open Label, Multi-centre, Non-interventional Post-marketing Surveillance (PMS) to Monitor the Safety and Effectiveness of Nebilet Administered in Korean Patients According to the Prescribing Information Conditions ----------------- Hypertension, Heart Failure Intervention / Treatment ----------------- * Drug: Nebivolol Participation Criteria ================= Eligibility Criteria ----------------- All subjects must satisfy the following criteria at PMS entry according to KFDA PMS regulation: Subjects with indication in the prescribing information Subjects administrated Nebivolol by physician's decision Subjects with no contraindication according to the prescribing information Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Patients administrated Nebivolol<br>There is only one group. This group includes patients administrated Nebivolol | Drug: Nebivolol<br>* patients administrated Nebivolol according to the prescribing information<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Occurrence of adverse events after Nebivolol administration | | 3months, 6months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Occurrence of unexpected or serious adverse event after Nebivolol administration and effectiveness of Occurrence of unexpected or serious adverse event after Nebivolol administration and effectiveness of Nebivolol | | 3 months, 6months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Nebivolol, PMS (post-marketing surveillance)

NCT03007485

Telehealth Pulmonary Rehabilitation for Hispanic and African-American Patients Admitted With Exacerbation of COPD

Chronic Obstructive Pulmonary Disease (COPD), also known as emphysema, is the leading cause of hospitalization for older adults in the U.S., and a leading cause of death. Although there is no cure for COPD, a program called pulmonary rehabilitation (PR), which combines exercise and education, can help decrease re-hospitalizations and improve patients' quality of life. Unfortunately, very few COPD Latino and African-American patients actually get PR. These patients are unlikely to get referrals or to be able to attend PR due to lack of insurance, lack of transportation, or lack of a PR center in their area. Telehealth is a way of using computers to deliver healthcare long-distance, eliminating the need for a patient to travel to receive care. By using telehealth for PR, the patient can exercise on a stationary bike in his or her home, while being supervised by videoconference by a respiratory therapist (RT). The RT can see the patient, and deliver education by videoconference, and the patient can see the RT, so the patient does not need to leave home to get PR.

Telehealth-delivered PR has been shown to be as effective as standard PR (patients go to an outpatient setting) at improving quality of life, and patients' exercise capacity. However, this has not been studied in the Latino and African-American population and it is not known how effective telehealth PR will be among this population.~For this study, the investigators hope to see if they can help COPD Latino and African-American patients with access to this needed resource through telehealth PR. They will compare standard PR and telehealth PR to determine if telehealth results in better outcomes for patients with moderate to severe COPD who were recently discharged from the hospital for COPD. The primary outcome the investigators will assess will be change in re-hospitalization rates. The secondary outcomes will include: change in quality of life, preparation to make decisions about clinical care, improved functional capacity, decreased dyspnea, anxiety, and depression.~The study will involve randomly assigning participants to make sure that they are just as likely to be in one group as the other to receive either: 1) referral for telehealth-delivered PR, or 2) referral to standard (outpatient) PR. Both PR programs consist of exercise and education twice a week for 8 weeks. The investigators will give the patients surveys to complete before they start the program and at the end of the program, to see if PR had any effect on the outcomes that are being measured. Patients will also be asked to participate in a qualitative interview and focus group to learn about the barriers they encountered even after receiving a referral to PR. These qualitative interviews will be conducted among a sample of participants representing those who withdrew, were lost-to-follow-up, completed PR and decided to only complete the surveys (i.e. not participate in PR).The investigators will enroll about 276 patients - with 138 patients in each group (telehealth PR or standard PR), so they can compare outcomes to see if telehealth PR was more, less, or equally effective as standard PR.

A Comprehensive Disease Management Program to Improve Quality of Life in Disparity Hispanic and African-American Patients Admitted With Exacerbation of Chronic Pulmonary Diseases

COPD Exacerbation

* Other: Telehealth Pulmonary Rehabilitation

Inclusion Criteria:~Adult patients with a diagnosis of COPD (defined by one pulmonary function tests (PFT) and who have not done pulmonary rehabilitation within the past 1 year and~Hispanic or African-American (as defined by the patient him/herself).~Exclusion Criteria:~individuals who completed PR in the past year or~those unable to exercise or follow directions as determined by their outpatient pulmonologist/cardiologist or~A diagnosis of dementia listed in the patient's electronic medical record~Patients who weigh more than 300 pounds

18 Years

All

No

Primary Purpose: Health Services Research Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Composite of COPD Hospital Readmission/Death Within 6 Month of Discharge | The investigators will analyze the change in the rate of patients' rehospitalizations following completion of pulmonary rehabilitation (PR). COPD Hospital Readmission were measured for Intention to Treat (ITT), medically cleared, and those who sat on the bike at least once. Composite of COPD hospital readmission or death within 6 months of discharge using all available (complete) data, and no imputation of missing data. Without adherence added, offset term omitted in the logistic regression. | 6 months post-discharge from hospitalization following COPD exacerbation |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Functional Capacity Before and After Pulmonary Rehabilitation 6-minute Walk Test (SPR) Tested in Meters) Between Day 1 and 8-weeks | The investigators will analyze the change in patients' functional capacity, as measured prior to beginning PR (Day 1), immediately following completion of PR (8 weeks). This measures the length the study participant walked/step (i.e. 2-minute step test (2MST)= how many steps the participant took, 6-minute walk test (6MWT)= the length the participant walked for in meters). Due to the limited space in TelePR participants home, they were only able to complete the 2MST, while SPR participants completed the 6MWT because the center had more space. | Prior to beginning PR (Day 1) and after completion of PR ( 8-weeks) | | Change in Self-reported Quality of Life: Longitudinal Outcomes. Surveys Administered Over the Entire Follow up Period Directly Before and After the PR Program | The investigators will analyze the change in patients' quality of life based on self-reported outcome measurements, as measured prior to beginning PR (Day 1), immediately following completion of PR (8 weeks), 6 months post-hospital discharge, 12 months post-hospital discharge.~COPD Assessment Test (CAT): Maximal Score: 40, Minimal Score: 0; lower score denotes improvement~Modified Medical Research Council Scale (MMRC): Maximal Score: 4, Minimal Score: 0; lower score denotes improvement~All PROMIS scales have a maximal score of 20 and minimal score for all scales is 4; lower score denotes improvement. | Prior to beginning PR, after completion of PR, and 6 months and12 months post-discharge from hospitalizations following COPD exacerbation | | Functional Capacity Before and After Pulmonary Rehabilitation (2-minute Step Test (TelePR) Tested in Steps | The investigators will analyze the change in patients' functional capacity, as measured prior to beginning PR (Day 1), immediately following completion of PR (8 weeks). This measures the length the study participant walked/step (i.e. 2-minute step test (2MST)= how many steps the participant took, 6-minute walk test (6MWT)= the length the participant walked for in meters). Due to the limited space in TelePR participants home, they were only able to complete the 2MST, while SPR participants completed the 6MWT because the center had more space. | Prior to beginning PR (Day 1) and after completion of PR ( 8-weeks) |

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | No Intervention: Standard of Care<br>Standard pulmonary rehabilitation | | | Experimental: Intervention<br>Telehealth delivered pulmonary rehabilitation | Other: Telehealth Pulmonary Rehabilitation<br>* Exercise bikes equipped with software that enables a respiratory therapist to remotely conduct a pulmonary rehabilitation session with a patient while he or she is at home (or at a local community center). The patient's vital signs are continually monitored and the RT is able to remotely alert 911 if a patient is in distress. Educational videos and stretching exercises are also incorporated into this session to mimic what a standard pulmonary rehabilitation session offers.<br>|

Telehealth Pulmonary Rehabilitation for Hispanic and African-American Patients Admitted With Exacerbation of COPD Study Overview ================= Brief Summary ----------------- Chronic Obstructive Pulmonary Disease (COPD), also known as emphysema, is the leading cause of hospitalization for older adults in the U.S., and a leading cause of death. Although there is no cure for COPD, a program called pulmonary rehabilitation (PR), which combines exercise and education, can help decrease re-hospitalizations and improve patients' quality of life. Unfortunately, very few COPD Latino and African-American patients actually get PR. These patients are unlikely to get referrals or to be able to attend PR due to lack of insurance, lack of transportation, or lack of a PR center in their area. Telehealth is a way of using computers to deliver healthcare long-distance, eliminating the need for a patient to travel to receive care. By using telehealth for PR, the patient can exercise on a stationary bike in his or her home, while being supervised by videoconference by a respiratory therapist (RT). The RT can see the patient, and deliver education by videoconference, and the patient can see the RT, so the patient does not need to leave home to get PR. Detailed Description ----------------- Telehealth-delivered PR has been shown to be as effective as standard PR (patients go to an outpatient setting) at improving quality of life, and patients' exercise capacity. However, this has not been studied in the Latino and African-American population and it is not known how effective telehealth PR will be among this population. For this study, the investigators hope to see if they can help COPD Latino and African-American patients with access to this needed resource through telehealth PR. They will compare standard PR and telehealth PR to determine if telehealth results in better outcomes for patients with moderate to severe COPD who were recently discharged from the hospital for COPD. The primary outcome the investigators will assess will be change in re-hospitalization rates. The secondary outcomes will include: change in quality of life, preparation to make decisions about clinical care, improved functional capacity, decreased dyspnea, anxiety, and depression. The study will involve randomly assigning participants to make sure that they are just as likely to be in one group as the other to receive either: 1) referral for telehealth-delivered PR, or 2) referral to standard (outpatient) PR. Both PR programs consist of exercise and education twice a week for 8 weeks. The investigators will give the patients surveys to complete before they start the program and at the end of the program, to see if PR had any effect on the outcomes that are being measured. Patients will also be asked to participate in a qualitative interview and focus group to learn about the barriers they encountered even after receiving a referral to PR. These qualitative interviews will be conducted among a sample of participants representing those who withdrew, were lost-to-follow-up, completed PR and decided to only complete the surveys (i.e. not participate in PR).The investigators will enroll about 276 patients - with 138 patients in each group (telehealth PR or standard PR), so they can compare outcomes to see if telehealth PR was more, less, or equally effective as standard PR. Official Title ----------------- A Comprehensive Disease Management Program to Improve Quality of Life in Disparity Hispanic and African-American Patients Admitted With Exacerbation of Chronic Pulmonary Diseases Conditions ----------------- COPD Exacerbation Intervention / Treatment ----------------- * Other: Telehealth Pulmonary Rehabilitation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Adult patients with a diagnosis of COPD (defined by one pulmonary function tests (PFT) and who have not done pulmonary rehabilitation within the past 1 year and Hispanic or African-American (as defined by the patient him/herself). Exclusion Criteria: individuals who completed PR in the past year or those unable to exercise or follow directions as determined by their outpatient pulmonologist/cardiologist or A diagnosis of dementia listed in the patient's electronic medical record Patients who weigh more than 300 pounds Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Health Services Research Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | No Intervention: Standard of Care<br>Standard pulmonary rehabilitation | | | Experimental: Intervention<br>Telehealth delivered pulmonary rehabilitation | Other: Telehealth Pulmonary Rehabilitation<br>* Exercise bikes equipped with software that enables a respiratory therapist to remotely conduct a pulmonary rehabilitation session with a patient while he or she is at home (or at a local community center). The patient's vital signs are continually monitored and the RT is able to remotely alert 911 if a patient is in distress. Educational videos and stretching exercises are also incorporated into this session to mimic what a standard pulmonary rehabilitation session offers.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Composite of COPD Hospital Readmission/Death Within 6 Month of Discharge | The investigators will analyze the change in the rate of patients' rehospitalizations following completion of pulmonary rehabilitation (PR). COPD Hospital Readmission were measured for Intention to Treat (ITT), medically cleared, and those who sat on the bike at least once. Composite of COPD hospital readmission or death within 6 months of discharge using all available (complete) data, and no imputation of missing data. Without adherence added, offset term omitted in the logistic regression. | 6 months post-discharge from hospitalization following COPD exacerbation | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Functional Capacity Before and After Pulmonary Rehabilitation 6-minute Walk Test (SPR) Tested in Meters) Between Day 1 and 8-weeks | The investigators will analyze the change in patients' functional capacity, as measured prior to beginning PR (Day 1), immediately following completion of PR (8 weeks). This measures the length the study participant walked/step (i.e. 2-minute step test (2MST)= how many steps the participant took, 6-minute walk test (6MWT)= the length the participant walked for in meters). Due to the limited space in TelePR participants home, they were only able to complete the 2MST, while SPR participants completed the 6MWT because the center had more space. | Prior to beginning PR (Day 1) and after completion of PR ( 8-weeks) | | Change in Self-reported Quality of Life: Longitudinal Outcomes. Surveys Administered Over the Entire Follow up Period Directly Before and After the PR Program | The investigators will analyze the change in patients' quality of life based on self-reported outcome measurements, as measured prior to beginning PR (Day 1), immediately following completion of PR (8 weeks), 6 months post-hospital discharge, 12 months post-hospital discharge. COPD Assessment Test (CAT): Maximal Score: 40, Minimal Score: 0; lower score denotes improvement Modified Medical Research Council Scale (MMRC): Maximal Score: 4, Minimal Score: 0; lower score denotes improvement All PROMIS scales have a maximal score of 20 and minimal score for all scales is 4; lower score denotes improvement. | Prior to beginning PR, after completion of PR, and 6 months and12 months post-discharge from hospitalizations following COPD exacerbation | | Functional Capacity Before and After Pulmonary Rehabilitation (2-minute Step Test (TelePR) Tested in Steps | The investigators will analyze the change in patients' functional capacity, as measured prior to beginning PR (Day 1), immediately following completion of PR (8 weeks). This measures the length the study participant walked/step (i.e. 2-minute step test (2MST)= how many steps the participant took, 6-minute walk test (6MWT)= the length the participant walked for in meters). Due to the limited space in TelePR participants home, they were only able to complete the 2MST, while SPR participants completed the 6MWT because the center had more space. | Prior to beginning PR (Day 1) and after completion of PR ( 8-weeks) |

NCT01893541

PROPRANOLOL PLUS LIGATION REDUCES RECURRENCE OF ESOPHAGEAL VARICES?

This prospective randomized controlled trial will compare endoscopic band ligation (EBL) with propranolol and EBL alone in primary prophylaxis of variceal bleeding among cirrhotic patients with high-risk varices.

BACKGROUND AND AIMS~Bleeding from esophagogastric varices (EV) is a major complication of portal hypertension. Beta-blockers are a well-established cornerstone of portal hypertension treatment. Band ligation is the best endoscopic treatment to prevent EV bleeding. The exact benefit of beta-blocker association to band ligation remains to be defined, especially for primary prophylaxis. This prospective randomized controlled trial will compare EBL with propranolol and EBL alone in primary prophylaxis of variceal bleeding among cirrhotic patients with high-risk varices. PATIENTS AND METHODS: The patients with high-risk varices will be randomly allocated to EBL plus propranolol (Group I) or EBL alone (Group II). EBL will be performed at 3-week interval till obliteration of varices. In Group I, incremental dosage of propranolol (sufficient to reduce heart rate to 55 beats/min or 25% reduction from baseline) will be administered and will be continued after obliteration of varices until the end of the study. The follow-up of patients will be 2 years. The primary outcome of this study will be EV recurrence during two years of follow-up. The secondary outcomes will be EV eradication, bleeding before eradication, mortality and complications during the same follow-up.

PROPRANOLOL ASSOCIATED WITH ENDOSCOPIC BAND LIGATION REDUCES RECURRENCE OF ESOPHAGEAL VARICES FOR PRIMARY PROPHYLAXIS OF VARICEAL BLEEDING?: A RANDOMIZED CONTROLLED TRIAL

CIRRHOSIS, ESOPHAGEAL VARICES

* Procedure: ENDOSCOPIC BAND LIGATION * Drug: PROPRANOLOL * Device: a multiband ligation device

Inclusion Criteria:~Liver cirrhosis with esophageal varices~Age between 18 and 78 years~Accept to participate~Exclusion Criteria:~Portal hypertension by schistosomiasis~Contraindications for propranolol use~Do not accept to participate

18 Years

78 Years

All

No

Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The primary outcome of this study will be esophageal varices recurrence | Esophageal varices recurrence will be defined as the reappearance of uninterrupted EV of any caliber, with or without red color signs in patients in which varices had been eradicated. | Two years |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The secondary outcomes of this study will be variceal eradication, bleeding before eradication, mortality and complications. | Esophageal varices eradication will be defined as absence of varices in the lower third of the esophagus Bleeding before EV eradication will be defined as any upper GI bleeding before EV obliteration. Bleeding will be considered from unknown origin when it will not possible to perform upper GI endoscopy in the first 48 hours after the bleeding episode; Mortality rate related to treatment will be defined as all cases of death resulting from bleeding due to EV, post-EBL ulceration, gastric varices, portal hypertensive gastropathy or any complication of treatment. Mortality rate non-related to treatment will be defined as death due to other causes; EBL complications will be divided in major (stenosis or esophageal perforation and bleeding due to post-EBL ulceration) and minor (chest pain, dysphagia, transient fever and esophageal ulceration with no bleeding postponing the subsequent treatment session). | two years |

CIRRHOTIC, VARICEAL BLEEDING, PRIMARY PROPHYLAXIS

Propranolol, Adrenergic beta-Antagonists, Adrenergic Antagonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs, Anti-Arrhythmia Agents, Antihypertensive Agents, Vasodilator Agents

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: EBL PLUS PROPRANOLOL<br>The EBL procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices were obliterated. The initial propranolol dose will be orally BID 40 mg, irrespective of patient's weight. The objective of the administration of propranolol will be induce beta-adrenergic blockade evaluated by reduction in heart rate to 55 bpm or a 25% drop in baseline heart rate. A baseline electrocardiogram will be obtained from all patients. The doses will be adjusted during weekly visits until beta-adrenergic blockade. After the adequate dose will be reached, the visits will be scheduled monthly during the first 3 months (until EV eradication) and then at a 3-month interval until the end of follow-up. | Procedure: ENDOSCOPIC BAND LIGATION<br>* The procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. All varices will be treated during the same session. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices will be obliterated.<br>Drug: PROPRANOLOL<br>* The initial propranolol dose will be orally BID 40 mg, irrespective of patient's weight. The objective of the administration of propranolol will be induce beta-adrenergic blockade evaluated by reduction in heart rate to 55 bpm or a 25% drop in baseline heart rate. A baseline electrocardiogram will be obtained from all patients. The doses will be adjusted during weekly visits until beta-adrenergic blockade. After the adequate dose will be reached, the visits will be scheduled monthly during the first 3 months (until EV eradication) and then at a 3-month interval until the end of follow-up.<br>Device: a multiband ligation device<br> <br> | | Active Comparator: ENDOSCOPIC BAND LIGATION<br>The procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. All varices will be treated during the same session. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices will be obliterated. | Procedure: ENDOSCOPIC BAND LIGATION<br>* The procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. All varices will be treated during the same session. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices will be obliterated.<br>|

PROPRANOLOL PLUS LIGATION REDUCES RECURRENCE OF ESOPHAGEAL VARICES? Study Overview ================= Brief Summary ----------------- This prospective randomized controlled trial will compare endoscopic band ligation (EBL) with propranolol and EBL alone in primary prophylaxis of variceal bleeding among cirrhotic patients with high-risk varices. Detailed Description ----------------- BACKGROUND AND AIMS Bleeding from esophagogastric varices (EV) is a major complication of portal hypertension. Beta-blockers are a well-established cornerstone of portal hypertension treatment. Band ligation is the best endoscopic treatment to prevent EV bleeding. The exact benefit of beta-blocker association to band ligation remains to be defined, especially for primary prophylaxis. This prospective randomized controlled trial will compare EBL with propranolol and EBL alone in primary prophylaxis of variceal bleeding among cirrhotic patients with high-risk varices. PATIENTS AND METHODS: The patients with high-risk varices will be randomly allocated to EBL plus propranolol (Group I) or EBL alone (Group II). EBL will be performed at 3-week interval till obliteration of varices. In Group I, incremental dosage of propranolol (sufficient to reduce heart rate to 55 beats/min or 25% reduction from baseline) will be administered and will be continued after obliteration of varices until the end of the study. The follow-up of patients will be 2 years. The primary outcome of this study will be EV recurrence during two years of follow-up. The secondary outcomes will be EV eradication, bleeding before eradication, mortality and complications during the same follow-up. Official Title ----------------- PROPRANOLOL ASSOCIATED WITH ENDOSCOPIC BAND LIGATION REDUCES RECURRENCE OF ESOPHAGEAL VARICES FOR PRIMARY PROPHYLAXIS OF VARICEAL BLEEDING?: A RANDOMIZED CONTROLLED TRIAL Conditions ----------------- CIRRHOSIS, ESOPHAGEAL VARICES Intervention / Treatment ----------------- * Procedure: ENDOSCOPIC BAND LIGATION * Drug: PROPRANOLOL * Device: a multiband ligation device Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Liver cirrhosis with esophageal varices Age between 18 and 78 years Accept to participate Exclusion Criteria: Portal hypertension by schistosomiasis Contraindications for propranolol use Do not accept to participate Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 78 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: EBL PLUS PROPRANOLOL<br>The EBL procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices were obliterated. The initial propranolol dose will be orally BID 40 mg, irrespective of patient's weight. The objective of the administration of propranolol will be induce beta-adrenergic blockade evaluated by reduction in heart rate to 55 bpm or a 25% drop in baseline heart rate. A baseline electrocardiogram will be obtained from all patients. The doses will be adjusted during weekly visits until beta-adrenergic blockade. After the adequate dose will be reached, the visits will be scheduled monthly during the first 3 months (until EV eradication) and then at a 3-month interval until the end of follow-up. | Procedure: ENDOSCOPIC BAND LIGATION<br>* The procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. All varices will be treated during the same session. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices will be obliterated.<br>Drug: PROPRANOLOL<br>* The initial propranolol dose will be orally BID 40 mg, irrespective of patient's weight. The objective of the administration of propranolol will be induce beta-adrenergic blockade evaluated by reduction in heart rate to 55 bpm or a 25% drop in baseline heart rate. A baseline electrocardiogram will be obtained from all patients. The doses will be adjusted during weekly visits until beta-adrenergic blockade. After the adequate dose will be reached, the visits will be scheduled monthly during the first 3 months (until EV eradication) and then at a 3-month interval until the end of follow-up.<br>Device: a multiband ligation device<br> <br> | | Active Comparator: ENDOSCOPIC BAND LIGATION<br>The procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. All varices will be treated during the same session. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices will be obliterated. | Procedure: ENDOSCOPIC BAND LIGATION<br>* The procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. All varices will be treated during the same session. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices will be obliterated.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The primary outcome of this study will be esophageal varices recurrence | Esophageal varices recurrence will be defined as the reappearance of uninterrupted EV of any caliber, with or without red color signs in patients in which varices had been eradicated. | Two years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The secondary outcomes of this study will be variceal eradication, bleeding before eradication, mortality and complications. | Esophageal varices eradication will be defined as absence of varices in the lower third of the esophagus Bleeding before EV eradication will be defined as any upper GI bleeding before EV obliteration. Bleeding will be considered from unknown origin when it will not possible to perform upper GI endoscopy in the first 48 hours after the bleeding episode; Mortality rate related to treatment will be defined as all cases of death resulting from bleeding due to EV, post-EBL ulceration, gastric varices, portal hypertensive gastropathy or any complication of treatment. Mortality rate non-related to treatment will be defined as death due to other causes; EBL complications will be divided in major (stenosis or esophageal perforation and bleeding due to post-EBL ulceration) and minor (chest pain, dysphagia, transient fever and esophageal ulceration with no bleeding postponing the subsequent treatment session). | two years | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- CIRRHOTIC, VARICEAL BLEEDING, PRIMARY PROPHYLAXIS

NCT05517226

Pharmacokinetics of Cotadutide in Participants With Hepatic Impairment

This study will assess the pharmacokinetics (PK), safety, and tolerability of a single subcutaneous injection of cotadutide in participants with mild, moderate or severe hepatic impairment compared to participants with normal hepatic function.

This study will consist of four cohorts (Cohort 1, Cohort 2, Cohort 3, and Cohort 4).~Participants will be assigned to each of the cohorts as per Child-Pugh classification:~Cohort 1: Mild hepatic impairment (Child-Pugh A), cotadutide 50 μg~Cohort 2: Moderate hepatic impairment (Child-Pugh B), cotadutide 50 μg~Cohort 3: Severe hepatic impairment (Child-Pugh C), cotadutide 50 μg~Cohort 4: Normal hepatic function, cotadutide 50 μg

A Phase I, Parallel-group, Multi-center, Open-label, Investigation of the Pharmacokinetics, Safety and Tolerability of a Single Subcutaneous Injection of Cotadutide in Participants With Mild, Moderate or Severe Hepatic Impairment Compared to Participants With Normal Hepatic Function

Hepatic Impairment

* Combination Product: Cotadutide

Inclusion Criteria:~Participant must be ≥ 18 to ≤ 85 years of age at the time of signing the Informed Consent Form (ICF).~Body mass index ≥ 18 kg/m2 to < 40 kg/m2.~Female participants of childbearing potential must use at least one highly effective form of birth control.~Capable of giving signed informed consent.~Participants with hepatic impairment only~- Diagnosis of chronic (≥ 6 months) and stable hepatic impairment (eg, no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 30 days prior to study Screening).~Exclusion Criteria:~All participants~History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to cotadutide.~Any clinically important abnormalities in rhythm, conduction or morphology of the 12-lead resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG as considered by the Investigator that may interfere with the interpretation of QT interval corrected for heart rate using Fridericia's formula (QTcF), including abnormal ST-T-wave morphology, or left ventricular hypertrophy~Prolonged QTcF > 470 ms or family history of long QT syndrome.~PR (PQ) interval shortening < 120 ms.~PR (PQ) interval prolongation (> 220 ms) intermittent or permanent second or third degree atrioventricular (AV) block, or AV dissociation.~Persistent or intermittent complete bundle branch block, or intraventricular conduction delay with QRS > 119 ms.~Any evidence of additional severe or uncontrolled systemic disease or laboratory finding that makes it unsafe for the participant to participate in the study.~Impaired renal function, defined as estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2 at Screening.~Any positive result on Screening for serum hepatitis B surface antigen, anti-Core HBV antibody, hepatitis C antibody, or human immunodeficiency virus (HIV).~Any sign and confirmation of coronavirus disease 2019 (COVID19) infection:~Participants with concurrent or previous use of a glucagon-like peptide-1 (GLP1) receptor agonist.~Use of prohibited prescribed or nonprescribed medication during the 2 weeks prior to the first administration of Investigational Medicinal Product (IMP) or longer if the medication has a long half-life.~History of neoplastic disease within 5 years prior to Screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer.~Presence of hepatocellular carcinoma or acute liver disease caused by an infection or drug toxicity.~Participants with hepatic impairment only~Severe portal hypertension or surgical porto-systemic shunts.~Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.~Clinically relevant hepatic encephalopathy.~Severe ascites defined as ascites requiring paracentesis and albumin at 4-week intervals or less.~Fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment within the 28-day Screening period.~Post liver transplantation.~Platelet count < 50 × 109/L and/or neutrophil count < 1.2 × 109/L and/or hemoglobin < 8.5 g/dL or INR >2.3.~Participants with normal hepatic function only~History or presence of hepatic disease or evidence of other known forms of known chronic liver disease.~History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.~Urinary albumin-to-creatinine ratio > 3 mg/μmol.

18 Years

85 Years

All

Accepts Healthy Volunteers

Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maximum observed plasma (peak) drug concentration [Cmax] | The Cmax of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Area under plasma concentration time curve from zero to infinity (AUCinf) | The AUCinf of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Area under the plasma concentration-curve from time zero to last quantifiable concentration (AUClast) | The AUClast of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Time to reach peak or maximum observed concentration or response following drug administration (tmax) | The tmax of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Terminal half-life (t½λz) | The t½λz of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Apparent total body clearance (CL/F) | The CL/F of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Apparent volume of distribution based on the terminal phase (Vz/F) | The Vz/F of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of participants with Adverse Events (AEs) | The safety, and tolerability of a single dose of cotadutide in participants with hepatic impairment will be assessed. | From time of first dose to the final follow-up visit (Day 29) | | Incidence of ADAs (anti-drug antibodies) | The safety, and tolerability of a single dose of cotadutide in participants with hepatic impairment will be assessed. | From time of first dose to the final follow-up visit (Day 29) |

Cotadutide, Hepatic impairment

Liver Diseases, Digestive System Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Cohort 1<br>Participants in each cohort will receive Dose A cotadutide subcutaneously. | Combination Product: Cotadutide<br>* Participants will receive cotadutide subcutaneously.<br>| | Experimental: Cohort 2<br>Participants in each cohort will receive Dose A cotadutide subcutaneously. | Combination Product: Cotadutide<br>* Participants will receive cotadutide subcutaneously.<br>| | Experimental: Cohort 3<br>Participants in each cohort will receive Dose A cotadutide subcutaneously. | Combination Product: Cotadutide<br>* Participants will receive cotadutide subcutaneously.<br>| | Experimental: Cohort 4<br>Participants in each cohort will receive Dose A cotadutide subcutaneously. | Combination Product: Cotadutide<br>* Participants will receive cotadutide subcutaneously.<br>|

Pharmacokinetics of Cotadutide in Participants With Hepatic Impairment Study Overview ================= Brief Summary ----------------- This study will assess the pharmacokinetics (PK), safety, and tolerability of a single subcutaneous injection of cotadutide in participants with mild, moderate or severe hepatic impairment compared to participants with normal hepatic function. Detailed Description ----------------- This study will consist of four cohorts (Cohort 1, Cohort 2, Cohort 3, and Cohort 4). Participants will be assigned to each of the cohorts as per Child-Pugh classification: Cohort 1: Mild hepatic impairment (Child-Pugh A), cotadutide 50 μg Cohort 2: Moderate hepatic impairment (Child-Pugh B), cotadutide 50 μg Cohort 3: Severe hepatic impairment (Child-Pugh C), cotadutide 50 μg Cohort 4: Normal hepatic function, cotadutide 50 μg Official Title ----------------- A Phase I, Parallel-group, Multi-center, Open-label, Investigation of the Pharmacokinetics, Safety and Tolerability of a Single Subcutaneous Injection of Cotadutide in Participants With Mild, Moderate or Severe Hepatic Impairment Compared to Participants With Normal Hepatic Function Conditions ----------------- Hepatic Impairment Intervention / Treatment ----------------- * Combination Product: Cotadutide Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Participant must be ≥ 18 to ≤ 85 years of age at the time of signing the Informed Consent Form (ICF). Body mass index ≥ 18 kg/m2 to < 40 kg/m2. Female participants of childbearing potential must use at least one highly effective form of birth control. Capable of giving signed informed consent. Participants with hepatic impairment only - Diagnosis of chronic (≥ 6 months) and stable hepatic impairment (eg, no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 30 days prior to study Screening). Exclusion Criteria: All participants History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to cotadutide. Any clinically important abnormalities in rhythm, conduction or morphology of the 12-lead resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG as considered by the Investigator that may interfere with the interpretation of QT interval corrected for heart rate using Fridericia's formula (QTcF), including abnormal ST-T-wave morphology, or left ventricular hypertrophy Prolonged QTcF > 470 ms or family history of long QT syndrome. PR (PQ) interval shortening < 120 ms. PR (PQ) interval prolongation (> 220 ms) intermittent or permanent second or third degree atrioventricular (AV) block, or AV dissociation. Persistent or intermittent complete bundle branch block, or intraventricular conduction delay with QRS > 119 ms. Any evidence of additional severe or uncontrolled systemic disease or laboratory finding that makes it unsafe for the participant to participate in the study. Impaired renal function, defined as estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2 at Screening. Any positive result on Screening for serum hepatitis B surface antigen, anti-Core HBV antibody, hepatitis C antibody, or human immunodeficiency virus (HIV). Any sign and confirmation of coronavirus disease 2019 (COVID19) infection: Participants with concurrent or previous use of a glucagon-like peptide-1 (GLP1) receptor agonist. Use of prohibited prescribed or nonprescribed medication during the 2 weeks prior to the first administration of Investigational Medicinal Product (IMP) or longer if the medication has a long half-life. History of neoplastic disease within 5 years prior to Screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer. Presence of hepatocellular carcinoma or acute liver disease caused by an infection or drug toxicity. Participants with hepatic impairment only Severe portal hypertension or surgical porto-systemic shunts. Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver. Clinically relevant hepatic encephalopathy. Severe ascites defined as ascites requiring paracentesis and albumin at 4-week intervals or less. Fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment within the 28-day Screening period. Post liver transplantation. Platelet count < 50 × 109/L and/or neutrophil count < 1.2 × 109/L and/or hemoglobin < 8.5 g/dL or INR >2.3. Participants with normal hepatic function only History or presence of hepatic disease or evidence of other known forms of known chronic liver disease. History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. Urinary albumin-to-creatinine ratio > 3 mg/μmol. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 85 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Cohort 1<br>Participants in each cohort will receive Dose A cotadutide subcutaneously. | Combination Product: Cotadutide<br>* Participants will receive cotadutide subcutaneously.<br>| | Experimental: Cohort 2<br>Participants in each cohort will receive Dose A cotadutide subcutaneously. | Combination Product: Cotadutide<br>* Participants will receive cotadutide subcutaneously.<br>| | Experimental: Cohort 3<br>Participants in each cohort will receive Dose A cotadutide subcutaneously. | Combination Product: Cotadutide<br>* Participants will receive cotadutide subcutaneously.<br>| | Experimental: Cohort 4<br>Participants in each cohort will receive Dose A cotadutide subcutaneously. | Combination Product: Cotadutide<br>* Participants will receive cotadutide subcutaneously.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maximum observed plasma (peak) drug concentration [Cmax] | The Cmax of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Area under plasma concentration time curve from zero to infinity (AUCinf) | The AUCinf of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Area under the plasma concentration-curve from time zero to last quantifiable concentration (AUClast) | The AUClast of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Time to reach peak or maximum observed concentration or response following drug administration (tmax) | The tmax of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Terminal half-life (t½λz) | The t½λz of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Apparent total body clearance (CL/F) | The CL/F of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | | Apparent volume of distribution based on the terminal phase (Vz/F) | The Vz/F of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed. | Day 1 to Day 3 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of participants with Adverse Events (AEs) | The safety, and tolerability of a single dose of cotadutide in participants with hepatic impairment will be assessed. | From time of first dose to the final follow-up visit (Day 29) | | Incidence of ADAs (anti-drug antibodies) | The safety, and tolerability of a single dose of cotadutide in participants with hepatic impairment will be assessed. | From time of first dose to the final follow-up visit (Day 29) | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Cotadutide, Hepatic impairment

NCT04226313

Self-sampling for Non-attenders to Cervical Cancer Screening

The trial will evaluate whether self-sampling and human papillomavirus (HPV) testing may increase cervical cancer screening attendance among under-screened women in Czech Republic. Different ways of offering self-sampling device will be evaluated.

Despite the existence of an effective cervical cancer screening in the Czech Republic, cervical cancer is the cause of about 800 new cases and 400 deaths every year. One of the major problem of the Czech cervical cancer screening is low participation. An effective strategy to increase cervical cancer screening attendance is one of the main challenges. The offering of self-sampling to the cervical cancer screening non-attenders could increase women's participation as was shown in several European countries.~The trial should determine acceptability of the self-sampling followed by HPV DNA test by Czech women and therefore usability of the self-sampling device to increase cervical cancer screening attendance among under-screened women. Three different approaches will be tested: women will receive a self-sampling device by mail (Arm A); receive a self-sampling device by gynecologist (Arm B); receive a self-sampling device by general practitioner (Arm C). Comparisons of the screening attendance among the arms will be made. To address also potential effects on inequities, the analyses will include comparisons by sociodemographic characteristics. Women from the database of commercial vendor will be included to the Arm A regardless of whether or not they participate in cervical cancer screening program. Women who do not participate in cytology-based cervical cancer screening program for at least three years will be included through their gynecologist (Arm B) or general practitioner (Arm C) database.~The second focus of the trial is the evaluation of high-risk human papillomavirus prevalence in screening population of Czech women (attenders and non-attenders of cervical cancer screening) since there are no relevant data for the Czech Republic. Study participants may volunteer for archiving of remaining biological materials for future studies.

Cervical Cancer Prevention Using Self-sampling and Human Papillomavirus Detection

Cervical Cancer, Cervical Dysplasia, Human Papillomavirus Infection

* Diagnostic Test: Self-sampling by Evalyn Brush * Diagnostic Test: Self sampling by Evalyn Brush home or in GP´s clinic

Inclusion Criteria:~Women with age 30-65 years; for arm A women > 65 years are allowed~Women live in the Czech Republic.~Women who have not participate in cervical cancer screening program in the Czech Republic for at least 3 years (Arm B and C).~Women with completed informed consent.~Women capable of self-sampling of cervicovaginal swab.~Exclusion Criteria:~Pregnant women.~Women with no sexual intercourse experience.~Women after hysterectomy including cervix.

30 Years

65 Years

Female

Accepts Healthy Volunteers

Primary Purpose: Screening Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Screening participation | Comparison of the percentages of women who return a cervicovaginal swab sampled by self-sampling device in different arms of the study. Identification of the best approach to address women who do not participate in standard cervical cancer screening program | 12 months | | Prevalence of high-risk HPV | Evaluation of the prevalence of high-risk human papillomavirus infection in screening population of Czech women within different arms of the study (attenders/non-attenders). | 12 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Sociodemographic characteristics | Comparison the distribution of sociodemographic characteristics (education, age, place of residence) and reasons for previous non-attendance for screening by intervention and attendance status in women who return a questionnaire. | 12 months |

human papillomavirus, HPV, self-sampling, cervicovaginal swab, cervical cancer screening, non-attendance

Papillomavirus Infections, Uterine Cervical Neoplasms, Uterine Cervical Dysplasia, Uterine Neoplasms, Genital Neoplasms, Female, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Uterine Cervical Diseases, Uterine Diseases, Genital Diseases, Female, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Genital Diseases, Sexually Transmitted Diseases, Viral, Sexually Transmitted Diseases, Communicable Diseases, Infections, DNA Virus Infections, Virus Diseases, Tumor Virus Infections, Disease Attributes, Pathologic Processes, Precancerous Conditions

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Self-sampling device sent at home<br>Women randomly selected from a commercial vendor database (both attenders and non-attenders) receive a mail inviting them to perform a cervicovaginal self-sampling at their home (with the device provided). Returned self-sampled swabs will be tested by CE-IVD-marked (Conformité Européenne, In Vitro Diagnostics) HPV diagnostic test validated for use in primary cervical cancer screening. The arm will include approx. 5000 participants. | Diagnostic Test: Self-sampling by Evalyn Brush<br>* Women will perform a cervicovaginal self-sampling at their home using Evalyn Brush.<br>| | Experimental: Self-sampling device sent by gynecologist(s)<br>Women selected from databases of cooperating gynecologists (non-attenders for at least 3 years) receive a mail inviting them to perform a cervicovaginal self-sampling at their home (with the device provided). Returned self-sampled swabs will be tested by CE-IVD-marked HPV diagnostic test validated for use in primary cervical cancer screening. The arm will include approx. 5000 participants. | Diagnostic Test: Self-sampling by Evalyn Brush<br>* Women will perform a cervicovaginal self-sampling at their home using Evalyn Brush.<br>| | Experimental: Self-sampling device obtained from general practitioner(s)<br>Women selected from databases of cooperating general practitioners (non-attenders for at least 3 years) receive a self-sampling device. Returned self-sampled swabs will be tested by CE-IVD-marked HPV diagnostic test validated for use in primary cervical cancer screening. The arm will include approx. 5000 participants. | Diagnostic Test: Self sampling by Evalyn Brush home or in GP´s clinic<br>* Women will perform a cervicovaginal self-sampling at their home or the GP´s clinic using Evalyn Brush<br>|

Self-sampling for Non-attenders to Cervical Cancer Screening Study Overview ================= Brief Summary ----------------- The trial will evaluate whether self-sampling and human papillomavirus (HPV) testing may increase cervical cancer screening attendance among under-screened women in Czech Republic. Different ways of offering self-sampling device will be evaluated. Detailed Description ----------------- Despite the existence of an effective cervical cancer screening in the Czech Republic, cervical cancer is the cause of about 800 new cases and 400 deaths every year. One of the major problem of the Czech cervical cancer screening is low participation. An effective strategy to increase cervical cancer screening attendance is one of the main challenges. The offering of self-sampling to the cervical cancer screening non-attenders could increase women's participation as was shown in several European countries. The trial should determine acceptability of the self-sampling followed by HPV DNA test by Czech women and therefore usability of the self-sampling device to increase cervical cancer screening attendance among under-screened women. Three different approaches will be tested: women will receive a self-sampling device by mail (Arm A); receive a self-sampling device by gynecologist (Arm B); receive a self-sampling device by general practitioner (Arm C). Comparisons of the screening attendance among the arms will be made. To address also potential effects on inequities, the analyses will include comparisons by sociodemographic characteristics. Women from the database of commercial vendor will be included to the Arm A regardless of whether or not they participate in cervical cancer screening program. Women who do not participate in cytology-based cervical cancer screening program for at least three years will be included through their gynecologist (Arm B) or general practitioner (Arm C) database. The second focus of the trial is the evaluation of high-risk human papillomavirus prevalence in screening population of Czech women (attenders and non-attenders of cervical cancer screening) since there are no relevant data for the Czech Republic. Study participants may volunteer for archiving of remaining biological materials for future studies. Official Title ----------------- Cervical Cancer Prevention Using Self-sampling and Human Papillomavirus Detection Conditions ----------------- Cervical Cancer, Cervical Dysplasia, Human Papillomavirus Infection Intervention / Treatment ----------------- * Diagnostic Test: Self-sampling by Evalyn Brush * Diagnostic Test: Self sampling by Evalyn Brush home or in GP´s clinic Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Women with age 30-65 years; for arm A women > 65 years are allowed Women live in the Czech Republic. Women who have not participate in cervical cancer screening program in the Czech Republic for at least 3 years (Arm B and C). Women with completed informed consent. Women capable of self-sampling of cervicovaginal swab. Exclusion Criteria: Pregnant women. Women with no sexual intercourse experience. Women after hysterectomy including cervix. Ages Eligible for Study ----------------- Minimum Age: 30 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Screening Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Self-sampling device sent at home<br>Women randomly selected from a commercial vendor database (both attenders and non-attenders) receive a mail inviting them to perform a cervicovaginal self-sampling at their home (with the device provided). Returned self-sampled swabs will be tested by CE-IVD-marked (Conformité Européenne, In Vitro Diagnostics) HPV diagnostic test validated for use in primary cervical cancer screening. The arm will include approx. 5000 participants. | Diagnostic Test: Self-sampling by Evalyn Brush<br>* Women will perform a cervicovaginal self-sampling at their home using Evalyn Brush.<br>| | Experimental: Self-sampling device sent by gynecologist(s)<br>Women selected from databases of cooperating gynecologists (non-attenders for at least 3 years) receive a mail inviting them to perform a cervicovaginal self-sampling at their home (with the device provided). Returned self-sampled swabs will be tested by CE-IVD-marked HPV diagnostic test validated for use in primary cervical cancer screening. The arm will include approx. 5000 participants. | Diagnostic Test: Self-sampling by Evalyn Brush<br>* Women will perform a cervicovaginal self-sampling at their home using Evalyn Brush.<br>| | Experimental: Self-sampling device obtained from general practitioner(s)<br>Women selected from databases of cooperating general practitioners (non-attenders for at least 3 years) receive a self-sampling device. Returned self-sampled swabs will be tested by CE-IVD-marked HPV diagnostic test validated for use in primary cervical cancer screening. The arm will include approx. 5000 participants. | Diagnostic Test: Self sampling by Evalyn Brush home or in GP´s clinic<br>* Women will perform a cervicovaginal self-sampling at their home or the GP´s clinic using Evalyn Brush<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Screening participation | Comparison of the percentages of women who return a cervicovaginal swab sampled by self-sampling device in different arms of the study. Identification of the best approach to address women who do not participate in standard cervical cancer screening program | 12 months | | Prevalence of high-risk HPV | Evaluation of the prevalence of high-risk human papillomavirus infection in screening population of Czech women within different arms of the study (attenders/non-attenders). | 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Sociodemographic characteristics | Comparison the distribution of sociodemographic characteristics (education, age, place of residence) and reasons for previous non-attendance for screening by intervention and attendance status in women who return a questionnaire. | 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- human papillomavirus, HPV, self-sampling, cervicovaginal swab, cervical cancer screening, non-attendance

NCT04280796

Changes in Affective Pain Processing in Human Volunteers

The experience of pain is more than the conscious perception of nociceptive signals. Emotional and motivational aspects accompany pain, leading to its aversiveness and motivation for avoidance. In chronic pain, a negative hedonic shift has been proposed that is characterized by disproportionally increased emotional-motivational compared to sensory-discriminative pain responses. Such a negative hedonic shift is, for example, mirrored in very high comorbidity rates of chronic pain and affective disorders such as depression and anxiety. The aim of this study is to develop methods that allow the differentiation of sensory-discriminative and emotional-motivational pain response and to characterize mechanisms of the negative hedonic shift.

The experience of pain is more than the conscious perception of nociceptive signals. Emotional and motivational aspects accompany pain, leading to its aversiveness and motivation for avoidance. In chronic pain, a negative hedonic shift has been proposed that is characterized by disproportionally increased emotional-motivational compared to sensory-discriminative pain responses. Such a negative hedonic shift is, for example, mirrored in very high comorbidity rates of chronic pain and affective disorders such as depression and anxiety. However, appropriate psychophysical methods to differentiate sensory-discriminative and emotional-motivational pain processing in humans are lacking. Therefore, only indirect evidence on the assumed negative hedonic shift in chronic pain is available, albeit understanding the mechanisms of such a shift would increase our knowledge on the development and maintenance of chronic pain in important ways with impact beyond pain research. The aim of this study is to develop methods that allow the differentiation of sensory-discriminative and emotional-motivational pain response and to characterize mechanisms of the negative hedonic shift.~A potential benefit of the study will be an increase in the knowledge on mechanisms of the development and maintenance of chronic pain with a focus on emotional-motivational processes likely also relevant in other diseases such as affective disorders.~This study involves only minimal risks for participants. The methods that will be used in the experimental investigations are within the range of standard procedures in pain research and experimental psychology and are frequently used in healthy participants and patients. Experimental pain stimulation will be adjusted to individual pain sensitivity, rendering the applied stimulation tolerable.~Substudy 1 Each participant will perform one testing session of approximately 1.5h duration at the Balgrist Campus, Balgrist University Hospital, Zurich. Healthy volunteers (N=31) will be recruited. The testing session will comprise a discrimination task and an avoidance task to assess sensory-discriminative and emotional-motivational pain components independently of each other. The tasks will be performed in counterbalanced order. After obtaining written informed consent, participants' individual heat pain threshold and tolerance will be determined, based on which the stimulation intensity to be used in the discrimination and the avoidance task will be calculated. After this assessment, participants either perform the discrimination or the avoidance task. Within the discrimination task, participants have to indicate whether they perceived a small increase in temperature or not. In the avoidance task, participants can avoid a painful stimulation by reacting fast enough to a visual cue. Participants will be randomly (balanced randomization) assigned to one of two learning conditions, either reinforcing successful discrimination or avoidance, to increase sensory-discriminative or emotional-motivational pain responses. Reinforcement, implemented by small monetary wins, will start depending on the condition after half the trials of the discrimination or the avoidance task. Subjective ratings of perceived pain intensity and unpleasantness will be assessed within both tasks as control variables to test whether increases in sensory-discriminative or emotional-motivational pain processing generalize to the subjective response channel. At the end of the testing session, participants will complete several questionnaires to investigate whether certain personality traits are related to learning capacity as tested in these tasks.~Substudy 2 Each participant will perform one testing session of approximately 1.5h duration at the Balgrist Campus, Balgrist University Hospital, Zurich. The sample will consist of patients with unspecific musculoskeletal chronic pain (N=31) and age- and sex-matched healthy controls (N=31). As in Substudy 1, the testing session will comprise the discrimination task and the avoidance task to assess sensory-discriminative and emotional-motivational pain components independently of each other. The tasks will be performed in counterbalanced order. After obtaining written informed consent, participants' individual heat pain threshold and tolerance will be determined, based on which the stimulation intensity to be used in the discrimination and the avoidance task will be calculated. After this assessment, participants either perform the discrimination or the avoidance task as in Substudy 1. In contrast to Substudy 1, reinforcement in the avoidance task will be implemented to decrease emotional-motivational pain responses because it is assumed that patients show already increased emotional-motivational compared to sensory-discriminative pain processing. Subjective ratings of perceived pain intensity and unpleasantness will be assessed within both tasks as control variables to test whether increases in sensory-discriminative or emotional-motivational pain processing generalize to the subjective response channel. At the end of the testing session, participants will complete several questionnaires, to investigate whether certain personality traits are related to heightened emotional-motivational pain processing.~Sample sizes for Substudy 1 and 2 are based on a priori sample size calculations using G*Power 3.1 with a desired medium effect size f=0.25, alpha=0.05, beta=0.80, repeated measures ANOVA between-within-subject designs, and an attrition rate of 10%. Outcome variables () will be analyzed in separate mixed model analyses for ANOVA designs with appropriate within- and between-subject factors. Associations of primary endpoints () with personality traits (secondary outcomes) will be analyzed using Person- or Spearman correlation coeffients, where appropriate. Significance levels will be set to 5%, adjusted with false discovery rate for multiple testing. Effect sizes will be calculated in terms of generalized η2 and Cohen's d.~Substudy 3 Each participant will perform one testing session of approximately 1.25h duration at the Balgrist Campus, Balgrist University Hospital, Zurich. Healthy volunteers (N=30) will be recruited. During testing session participants will perform a psychophysical task to assess metacognition in pain perception as an indicator of the cognitive-evaluative pain component. The objective is to assess whether metacognition on pain perception are involved and subjective ratings of perceived pain and how metacognition relates to pain intensity. After obtaining written informed consent, participants' individual heat pain threshold and tolerance will be determined, based on which the stimulation intensity to be used in the experiment will be calculated. After this assessment, participants perform the cognitive pain task. Within this task, participants have to indicate whether they perceived a first or second heat pain stimulus as higher in intensity, whether the higher one was perceived as painful or not, and their confidence in both these answers. In addition, participants will complete several questionnaires to investigate whether certain personality traits and personal states are related to metacognition in pain.~The sample size of Substudy 3 is determined according to Kreft and Leeuw (2007) after which a great enough power will be reached with a sample size of 30 participants and 30 observations to identify cross-level interactions. Substudy 3 follows a within subject design with repeated measures. The tasks that will be performed by each participant include the within-subject factor 'temperature difference' (differences in temperature between first and second stimulus) and the within-subject factor 'temperature level' (temperature relative to individual pain threshold of each stimulus). The order of the different conditions in each task will be applied using a balanced pseudo-randomized order. For testing hypothesis 1ai, 1bi and 1c t-test will be conducted. For Hypothesis 1aii and 1bii chi square tests are planned. To test hypothesis 2a, 2c and 3 logistic hierarchic liner models and for hypothesis 2b and 2d hierarchic linear models will be performed.~Within this study methods that allow the separation of different components of the perception of pain will be developed and validated and which are currently not available. In addition, based on theses methods, a human model on how such components of pain can dissociate will be developed, thereby allowing investigating a prominent assumption on factors that crucially contribute to the development and maintenance of chronic pain. The expected results will form the basis for the development of novel mechanism-based pain therapies.~Psychophysical methods based on experimental psychology and pain research will be used, which have been shown before to be successful in investigating different aspects of pain perception and the modulation of pain perception. The methods used are in the standard range of methods from human pain research and experimental psychology and hold only minimal risk for participants (see above Risk / Benefit Assessment).

Mechanisms of Emotional-motivational Pain Processing in Health and Disease

Pain, Acute, Pain, Chronic, Low Back Pain

* Behavioral: psychophysical tasks * Behavioral: cognitive task

For Healthy participants~Inclusion Criteria:~good overall health status~sufficient knowledge of German or English to follow instructions~ability to give written informed consent~Exclusion Criteria:~pain longer than >3 consecutive days and on more than 30 days within the last 12 months~major psychiatric or neurological disorders, and substance abuse~consumption of alcohol, illegal drugs, and analgesic drug within 24 hours before testing~For chronic pain patients~Inclusion Criteria:~unspecific musculoskeletal chronic pain~sufficient knowledge of German or English to follow instructions~ability to give written informed consent~Exclusion Criteria:~major psychiatric or neurological disorders, excluding depression and anxiety, and substance abuse~consumption of alcohol, illegal drugs, and analgesic drugs within 24 hours before testing

18 Years

60 Years

All

Accepts Healthy Volunteers

Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Crossover Assignment Interventional Model Description: Study comprises an intervention that is neither a therapeutic or transplant product nor a transplant. Study involves minimal risks for participants. Used methods are within the range of standard methods frequently used in pain research. All participants will perform 2 psychophysical tasks to assess sensory-discriminative & emotional-motivational pain responses independently from each other.~Substudy1: An operant learning paradigm will be implemented to dissociate these responses, increasing the sensory-discriminative compared to emotional-motivational pain responses by contingent monetary reinforcement & vice versa. Substudy2: Responses of chronic pain patients will be compared to those of healthy participants to characterize possible alterations. Operant learning will be operationalized to decrease emotional-motivational pain responses, which are assumed to be increased in patients. Substudy3: Participants will perform a psychophysical task to assess metacognition in pain perception. Masking: Single

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | ratio of sensory to emotional pain responses | Ratio of the number of correct responses (%) in a task assessing sensory-discriminative pain responses to number of correct responses (%) in a task assessing emotional-motivational pain responses. | during the procedure |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | reaction time (RT) | reaction times | during the procedure | | pain threshold | Individual pain threshold assessed with experimental heat pain | baseline | | pain tolerance | Individual pain tolerance assessed with experimental heat pain | baseline | | perceived pain intensity | Individual perceived pain intensity assessed with experimental heat pain | during the procedure | | perceived pain unpleasantness | Individual perceived pain unpleasantness assessed with experimental heat pain | during the procedure | | Fear of Pain Questionnaire (FPQ-III) | FPQ-III is one questionnaire which is a widely used to assess the fear of pain (FOP) in clinical and non clinical samples. It is one self-report instrument that was developed specifically to assess fear of different stimuli usually causing pain.~Time duration <5minutes Five point Likert scale Score range (30-150) A higher score indicates higher fear of pain, no cut-off values | during the procedure at day one | | Pain Catastrophizing Scale (PCS) | The PCS was developed in 1995 at the University Centre for Research on Pain and Disability in order to facilitate research on the mechanisms by which catastrophizing impacts on pain experience. Catastrophizing is currently defined as: an exaggerated negative mental set brought to bear during actual or anticipated painful experience.~Time duration less than 5minutes Five point Likert scale Score range (0-52) <20 low risk for development of chronicity 20-30 moderate risk for development of chronicity >30 high risk for development of chronicity | during the procedure at day one | | Fear of Avoidance Beliefs FABQ | FABQ focuses on how a patient's fear avoidance beliefs about physical activity and work may affect and contribute to their low back pain and resulting disability~Time duration 5-10minutes Seven point Likert scale Score range (0-96) Higher score indicates fear avoidance behaviors | during the procedure at day one | | Personal Evaluation Inventory (PEI) | PEI asses among other things ones trait confidence which might be related to metacognition in pain. | during procedure | | skin conductance responses | individual skin conductance reaction on heat stimuli during the behavioural task | during procedure | | confidence ratings on forced choice questions | Answers on forced-choice questions on which one of two heat stimuli was more intense and whether this one was perceived as painful, ratings of confidence. The answers on the forces-choice questions together with their ratings of confindence in these answers provide a measurement of metacognition. | during procedure |

acute pain, chronic pain, low back pain, hedonic shift, emotional-motivation components of pain, sensory-discriminative components of pain, operant conditioning, metacognition

Back Pain, Low Back Pain, Acute Pain, Chronic Pain, Pain, Neurologic Manifestations

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Substudy 1<br>All participants will perform two psychophysical tasks to assess sensory-discriminative and emotional-motivational pain responses independently from each other. No arms will perform. In addition, in Substudy 1 an operant learning paradigm will be implemented to dissociate these responses, increasing the sensory-discriminative pain responses compared to emotional-motivational pain responses by contingent monetary reinforcement and vice versa.~Primary objectives:~To develop psychophysical methods that allow the independent assessment of sensory-discriminative and emotional-motivational pain responses and~to show that emotional-motivational and sensory-discriminative pain components can be dissociated~Secondary objective:~To assess whether fear of pain, fear-avoidance beliefs, pain catastrophizing, and sensation seeking as personality traits can explain variations in how strongly sensory-discriminative and emotional-motivational pain responses can be dissociated | Behavioral: psychophysical tasks<br>* All participants perform two psychophysical tasks to assess sensory-discriminative and emotional-motivational pain responses independently from each other.~In addition, in Substudy 1 an operant learning paradigm will be implement to dissociate these responses, increasing the sensory-discriminative pain responses compared to emotional-motivational pain responses by contingent monetary reinforcement or vice versa.~In Substudy 2, responses of chronic pain patients will be compared to those of healthy participants to characterize possible alterations and operant learning will be operationalized to decrease emotional-motivational pain responses, which are assumed to be already increased in the patients.<br>| | Experimental: Substudy 2<br>All participants will perform two psychophysical tasks to assess sensory-discriminative and emotional-motivational pain responses independently from each other. No arms will perform. In addition, in Substudy 2, responses of chronic pain patients will be compared to those of healthy participants to characterize possible alterations in the patients and operant learning will be operationalized to decrease emotional-motivational pain responses, which are assumed to be already increased in the patients.~Primary objective:~To demonstrate that in chronic pain patients, emotional-motivational pain responses are increased relative to sensory-discriminative pain responses~Secondary objective:~To assess whether fear of pain, fear-avoidance beliefs, pain catastrophizing, and sensation seeking as personality traits can explain variations in the present dissociation of sensory-discriminative and emotional-motivational pain responses in chronic pain patients | Behavioral: psychophysical tasks<br>* All participants perform two psychophysical tasks to assess sensory-discriminative and emotional-motivational pain responses independently from each other.~In addition, in Substudy 1 an operant learning paradigm will be implement to dissociate these responses, increasing the sensory-discriminative pain responses compared to emotional-motivational pain responses by contingent monetary reinforcement or vice versa.~In Substudy 2, responses of chronic pain patients will be compared to those of healthy participants to characterize possible alterations and operant learning will be operationalized to decrease emotional-motivational pain responses, which are assumed to be already increased in the patients.<br>| | Experimental: Substudy 3<br>All participants will perform a psychophysical task to assess metacognition in pain perception as an indicator of the cognitive-evaluative pain component. No arms will perform.~Primary objective:~To assess whether metacognition on pain perception are involved and subjective ratings of perceived pain and how metacognition relates to pain intensity.~Secondary objective:~To assess whether confidentiality as a personality trait , pain catastrophizing, and skin conductance responses are related to metacognition in pain. | Behavioral: cognitive task<br>* In Substudy 3 participants will perform a psychophysical task to assess metacognition in pain perception as an indicator of the cognitive-evaluative pain component.<br>|

Changes in Affective Pain Processing in Human Volunteers Study Overview ================= Brief Summary ----------------- The experience of pain is more than the conscious perception of nociceptive signals. Emotional and motivational aspects accompany pain, leading to its aversiveness and motivation for avoidance. In chronic pain, a negative hedonic shift has been proposed that is characterized by disproportionally increased emotional-motivational compared to sensory-discriminative pain responses. Such a negative hedonic shift is, for example, mirrored in very high comorbidity rates of chronic pain and affective disorders such as depression and anxiety. The aim of this study is to develop methods that allow the differentiation of sensory-discriminative and emotional-motivational pain response and to characterize mechanisms of the negative hedonic shift. Detailed Description ----------------- The experience of pain is more than the conscious perception of nociceptive signals. Emotional and motivational aspects accompany pain, leading to its aversiveness and motivation for avoidance. In chronic pain, a negative hedonic shift has been proposed that is characterized by disproportionally increased emotional-motivational compared to sensory-discriminative pain responses. Such a negative hedonic shift is, for example, mirrored in very high comorbidity rates of chronic pain and affective disorders such as depression and anxiety. However, appropriate psychophysical methods to differentiate sensory-discriminative and emotional-motivational pain processing in humans are lacking. Therefore, only indirect evidence on the assumed negative hedonic shift in chronic pain is available, albeit understanding the mechanisms of such a shift would increase our knowledge on the development and maintenance of chronic pain in important ways with impact beyond pain research. The aim of this study is to develop methods that allow the differentiation of sensory-discriminative and emotional-motivational pain response and to characterize mechanisms of the negative hedonic shift. A potential benefit of the study will be an increase in the knowledge on mechanisms of the development and maintenance of chronic pain with a focus on emotional-motivational processes likely also relevant in other diseases such as affective disorders. This study involves only minimal risks for participants. The methods that will be used in the experimental investigations are within the range of standard procedures in pain research and experimental psychology and are frequently used in healthy participants and patients. Experimental pain stimulation will be adjusted to individual pain sensitivity, rendering the applied stimulation tolerable. Substudy 1 Each participant will perform one testing session of approximately 1.5h duration at the Balgrist Campus, Balgrist University Hospital, Zurich. Healthy volunteers (N=31) will be recruited. The testing session will comprise a discrimination task and an avoidance task to assess sensory-discriminative and emotional-motivational pain components independently of each other. The tasks will be performed in counterbalanced order. After obtaining written informed consent, participants' individual heat pain threshold and tolerance will be determined, based on which the stimulation intensity to be used in the discrimination and the avoidance task will be calculated. After this assessment, participants either perform the discrimination or the avoidance task. Within the discrimination task, participants have to indicate whether they perceived a small increase in temperature or not. In the avoidance task, participants can avoid a painful stimulation by reacting fast enough to a visual cue. Participants will be randomly (balanced randomization) assigned to one of two learning conditions, either reinforcing successful discrimination or avoidance, to increase sensory-discriminative or emotional-motivational pain responses. Reinforcement, implemented by small monetary wins, will start depending on the condition after half the trials of the discrimination or the avoidance task. Subjective ratings of perceived pain intensity and unpleasantness will be assessed within both tasks as control variables to test whether increases in sensory-discriminative or emotional-motivational pain processing generalize to the subjective response channel. At the end of the testing session, participants will complete several questionnaires to investigate whether certain personality traits are related to learning capacity as tested in these tasks. Substudy 2 Each participant will perform one testing session of approximately 1.5h duration at the Balgrist Campus, Balgrist University Hospital, Zurich. The sample will consist of patients with unspecific musculoskeletal chronic pain (N=31) and age- and sex-matched healthy controls (N=31). As in Substudy 1, the testing session will comprise the discrimination task and the avoidance task to assess sensory-discriminative and emotional-motivational pain components independently of each other. The tasks will be performed in counterbalanced order. After obtaining written informed consent, participants' individual heat pain threshold and tolerance will be determined, based on which the stimulation intensity to be used in the discrimination and the avoidance task will be calculated. After this assessment, participants either perform the discrimination or the avoidance task as in Substudy 1. In contrast to Substudy 1, reinforcement in the avoidance task will be implemented to decrease emotional-motivational pain responses because it is assumed that patients show already increased emotional-motivational compared to sensory-discriminative pain processing. Subjective ratings of perceived pain intensity and unpleasantness will be assessed within both tasks as control variables to test whether increases in sensory-discriminative or emotional-motivational pain processing generalize to the subjective response channel. At the end of the testing session, participants will complete several questionnaires, to investigate whether certain personality traits are related to heightened emotional-motivational pain processing. Sample sizes for Substudy 1 and 2 are based on a priori sample size calculations using G*Power 3.1 with a desired medium effect size f=0.25, alpha=0.05, beta=0.80, repeated measures ANOVA between-within-subject designs, and an attrition rate of 10%. Outcome variables () will be analyzed in separate mixed model analyses for ANOVA designs with appropriate within- and between-subject factors. Associations of primary endpoints () with personality traits (secondary outcomes) will be analyzed using Person- or Spearman correlation coeffients, where appropriate. Significance levels will be set to 5%, adjusted with false discovery rate for multiple testing. Effect sizes will be calculated in terms of generalized η2 and Cohen's d. Substudy 3 Each participant will perform one testing session of approximately 1.25h duration at the Balgrist Campus, Balgrist University Hospital, Zurich. Healthy volunteers (N=30) will be recruited. During testing session participants will perform a psychophysical task to assess metacognition in pain perception as an indicator of the cognitive-evaluative pain component. The objective is to assess whether metacognition on pain perception are involved and subjective ratings of perceived pain and how metacognition relates to pain intensity. After obtaining written informed consent, participants' individual heat pain threshold and tolerance will be determined, based on which the stimulation intensity to be used in the experiment will be calculated. After this assessment, participants perform the cognitive pain task. Within this task, participants have to indicate whether they perceived a first or second heat pain stimulus as higher in intensity, whether the higher one was perceived as painful or not, and their confidence in both these answers. In addition, participants will complete several questionnaires to investigate whether certain personality traits and personal states are related to metacognition in pain. The sample size of Substudy 3 is determined according to Kreft and Leeuw (2007) after which a great enough power will be reached with a sample size of 30 participants and 30 observations to identify cross-level interactions. Substudy 3 follows a within subject design with repeated measures. The tasks that will be performed by each participant include the within-subject factor 'temperature difference' (differences in temperature between first and second stimulus) and the within-subject factor 'temperature level' (temperature relative to individual pain threshold of each stimulus). The order of the different conditions in each task will be applied using a balanced pseudo-randomized order. For testing hypothesis 1ai, 1bi and 1c t-test will be conducted. For Hypothesis 1aii and 1bii chi square tests are planned. To test hypothesis 2a, 2c and 3 logistic hierarchic liner models and for hypothesis 2b and 2d hierarchic linear models will be performed. Within this study methods that allow the separation of different components of the perception of pain will be developed and validated and which are currently not available. In addition, based on theses methods, a human model on how such components of pain can dissociate will be developed, thereby allowing investigating a prominent assumption on factors that crucially contribute to the development and maintenance of chronic pain. The expected results will form the basis for the development of novel mechanism-based pain therapies. Psychophysical methods based on experimental psychology and pain research will be used, which have been shown before to be successful in investigating different aspects of pain perception and the modulation of pain perception. The methods used are in the standard range of methods from human pain research and experimental psychology and hold only minimal risk for participants (see above Risk / Benefit Assessment). Official Title ----------------- Mechanisms of Emotional-motivational Pain Processing in Health and Disease Conditions ----------------- Pain, Acute, Pain, Chronic, Low Back Pain Intervention / Treatment ----------------- * Behavioral: psychophysical tasks * Behavioral: cognitive task Participation Criteria ================= Eligibility Criteria ----------------- For Healthy participants Inclusion Criteria: good overall health status sufficient knowledge of German or English to follow instructions ability to give written informed consent Exclusion Criteria: pain longer than >3 consecutive days and on more than 30 days within the last 12 months major psychiatric or neurological disorders, and substance abuse consumption of alcohol, illegal drugs, and analgesic drug within 24 hours before testing For chronic pain patients Inclusion Criteria: unspecific musculoskeletal chronic pain sufficient knowledge of German or English to follow instructions ability to give written informed consent Exclusion Criteria: major psychiatric or neurological disorders, excluding depression and anxiety, and substance abuse consumption of alcohol, illegal drugs, and analgesic drugs within 24 hours before testing Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 60 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Crossover Assignment Interventional Model Description: Study comprises an intervention that is neither a therapeutic or transplant product nor a transplant. Study involves minimal risks for participants. Used methods are within the range of standard methods frequently used in pain research. All participants will perform 2 psychophysical tasks to assess sensory-discriminative & emotional-motivational pain responses independently from each other. Substudy1: An operant learning paradigm will be implemented to dissociate these responses, increasing the sensory-discriminative compared to emotional-motivational pain responses by contingent monetary reinforcement & vice versa. Substudy2: Responses of chronic pain patients will be compared to those of healthy participants to characterize possible alterations. Operant learning will be operationalized to decrease emotional-motivational pain responses, which are assumed to be increased in patients. Substudy3: Participants will perform a psychophysical task to assess metacognition in pain perception. Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Substudy 1<br>All participants will perform two psychophysical tasks to assess sensory-discriminative and emotional-motivational pain responses independently from each other. No arms will perform. In addition, in Substudy 1 an operant learning paradigm will be implemented to dissociate these responses, increasing the sensory-discriminative pain responses compared to emotional-motivational pain responses by contingent monetary reinforcement and vice versa. Primary objectives: To develop psychophysical methods that allow the independent assessment of sensory-discriminative and emotional-motivational pain responses and to show that emotional-motivational and sensory-discriminative pain components can be dissociated Secondary objective: To assess whether fear of pain, fear-avoidance beliefs, pain catastrophizing, and sensation seeking as personality traits can explain variations in how strongly sensory-discriminative and emotional-motivational pain responses can be dissociated | Behavioral: psychophysical tasks<br>* All participants perform two psychophysical tasks to assess sensory-discriminative and emotional-motivational pain responses independently from each other. In addition, in Substudy 1 an operant learning paradigm will be implement to dissociate these responses, increasing the sensory-discriminative pain responses compared to emotional-motivational pain responses by contingent monetary reinforcement or vice versa. In Substudy 2, responses of chronic pain patients will be compared to those of healthy participants to characterize possible alterations and operant learning will be operationalized to decrease emotional-motivational pain responses, which are assumed to be already increased in the patients.<br>| | Experimental: Substudy 2<br>All participants will perform two psychophysical tasks to assess sensory-discriminative and emotional-motivational pain responses independently from each other. No arms will perform. In addition, in Substudy 2, responses of chronic pain patients will be compared to those of healthy participants to characterize possible alterations in the patients and operant learning will be operationalized to decrease emotional-motivational pain responses, which are assumed to be already increased in the patients. Primary objective: To demonstrate that in chronic pain patients, emotional-motivational pain responses are increased relative to sensory-discriminative pain responses Secondary objective: To assess whether fear of pain, fear-avoidance beliefs, pain catastrophizing, and sensation seeking as personality traits can explain variations in the present dissociation of sensory-discriminative and emotional-motivational pain responses in chronic pain patients | Behavioral: psychophysical tasks<br>* All participants perform two psychophysical tasks to assess sensory-discriminative and emotional-motivational pain responses independently from each other. In addition, in Substudy 1 an operant learning paradigm will be implement to dissociate these responses, increasing the sensory-discriminative pain responses compared to emotional-motivational pain responses by contingent monetary reinforcement or vice versa. In Substudy 2, responses of chronic pain patients will be compared to those of healthy participants to characterize possible alterations and operant learning will be operationalized to decrease emotional-motivational pain responses, which are assumed to be already increased in the patients.<br>| | Experimental: Substudy 3<br>All participants will perform a psychophysical task to assess metacognition in pain perception as an indicator of the cognitive-evaluative pain component. No arms will perform. Primary objective: To assess whether metacognition on pain perception are involved and subjective ratings of perceived pain and how metacognition relates to pain intensity. Secondary objective: To assess whether confidentiality as a personality trait , pain catastrophizing, and skin conductance responses are related to metacognition in pain. | Behavioral: cognitive task<br>* In Substudy 3 participants will perform a psychophysical task to assess metacognition in pain perception as an indicator of the cognitive-evaluative pain component.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | ratio of sensory to emotional pain responses | Ratio of the number of correct responses (%) in a task assessing sensory-discriminative pain responses to number of correct responses (%) in a task assessing emotional-motivational pain responses. | during the procedure | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | reaction time (RT) | reaction times | during the procedure | | pain threshold | Individual pain threshold assessed with experimental heat pain | baseline | | pain tolerance | Individual pain tolerance assessed with experimental heat pain | baseline | | perceived pain intensity | Individual perceived pain intensity assessed with experimental heat pain | during the procedure | | perceived pain unpleasantness | Individual perceived pain unpleasantness assessed with experimental heat pain | during the procedure | | Fear of Pain Questionnaire (FPQ-III) | FPQ-III is one questionnaire which is a widely used to assess the fear of pain (FOP) in clinical and non clinical samples. It is one self-report instrument that was developed specifically to assess fear of different stimuli usually causing pain. Time duration <5minutes Five point Likert scale Score range (30-150) A higher score indicates higher fear of pain, no cut-off values | during the procedure at day one | | Pain Catastrophizing Scale (PCS) | The PCS was developed in 1995 at the University Centre for Research on Pain and Disability in order to facilitate research on the mechanisms by which catastrophizing impacts on pain experience. Catastrophizing is currently defined as: an exaggerated negative mental set brought to bear during actual or anticipated painful experience. Time duration less than 5minutes Five point Likert scale Score range (0-52) <20 low risk for development of chronicity 20-30 moderate risk for development of chronicity >30 high risk for development of chronicity | during the procedure at day one | | Fear of Avoidance Beliefs FABQ | FABQ focuses on how a patient's fear avoidance beliefs about physical activity and work may affect and contribute to their low back pain and resulting disability Time duration 5-10minutes Seven point Likert scale Score range (0-96) Higher score indicates fear avoidance behaviors | during the procedure at day one | | Personal Evaluation Inventory (PEI) | PEI asses among other things ones trait confidence which might be related to metacognition in pain. | during procedure | | skin conductance responses | individual skin conductance reaction on heat stimuli during the behavioural task | during procedure | | confidence ratings on forced choice questions | Answers on forced-choice questions on which one of two heat stimuli was more intense and whether this one was perceived as painful, ratings of confidence. The answers on the forces-choice questions together with their ratings of confindence in these answers provide a measurement of metacognition. | during procedure | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- acute pain, chronic pain, low back pain, hedonic shift, emotional-motivation components of pain, sensory-discriminative components of pain, operant conditioning, metacognition

NCT03144284

Assessment of Knowledge, Attitude, and Practice of Minimal Intervention Dentistry in a Group of Dental Interns

Minimal intervention dentistry (MID) is a modern medical approach that aims to maximize preservation of healthy dental tissues. When operative intervention is required it is as minimally invasive as possible. This study will assess the knowledge of a group of dental interns regarding minimal intervention dentistry in Egypt and whether this knowledge is translated into positive attitude and practice among them.

Healthy oral tissues enable the child to eat, speak and socialize which contributes to general wellbeing. Dental caries during childhood is a major public health problem and throughout the 20th century, the dominant practice patterns of managing dental caries relied on the purely surgical approach of G.V Black such as the concept of extension for prevention. One of the drawbacks of this approach is an unnecessary removal of healthy oral tissues.~Comprehensive knowledge of dental cariology, advances in dental restorative materials and modern diagnostic devices are changing pediatric restorative dentistry.~minimal intervention dentistry (MID) is a modern medical approach that aims to maximize preservation of healthy dental tissues based on individualized patient care of early detection of disease, risk assessment diagnosis, and prevention. When operative intervention is required it is as minimally invasive as possible.~There is insufficient information about knowledge and practice of modern dental approaches including minimal intervention dentistry among dental interns in Egypt. Available studies concerned with this subject were not done in Egypt.~Due to this shortage of information, the application of MID in the Egyptian society cannot be fully assessed, and problems associated with its practice cannot be identified and solved. This shortage of information may also deprive children of getting benefits of MID.~Thus; this study will assess the knowledge of a group of dental interns regarding minimal intervention dentistry in Egypt, and whether this knowledge is translated into positive attitude and practice among them.~Knowledge, attitude, and practice (KAP) surveys can be used to identify knowledge gaps and culturally related misconceptions of new health approaches or interventions. They can determine factors influencing behaviors that are not known, and how and why people practice certain health behaviors.~KAP surveys can be also used to identify needs, problems and barriers, as well as solutions for improving quality and accessibility of health services by studying factors and possible determinants influencing treatment decisions.~This study aims to identify deficiencies (if present) in knowledge, attitude, and practice of MID among a group of dental interns in Egypt.

Assessment of Knowledge, Attitude, and Practice of Minimal Intervention Dentistry in a Group of Dental Interns in Egypt: A Cross-sectional Study

Pediatric Dentistry

* Other: Knowledge, attitude, and practice survey

Inclusion Criteria:~Dental interns attending pediatric dentistry in the faculty of dentistry, Cairo University.~Exclusion Criteria:~Interns refusing to participate in the study.

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Knowledge, attitude and practice mean score | Scores will be calculated according to the options selected by dental interns. The primary outcome is the mean score of the knowledge, attitude and practice survey. | Through study completion, an average of 1 year. |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | response rate | percentage of dental interns who agree to participate in the study. | Through study completion, an average of 1 year. |

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | dental interns<br>dental interns in pediatric dentistry department, faculty of dentistry, Cairo University. | Other: Knowledge, attitude, and practice survey<br>* A knowledge, attitude, and practice questionnaire is going to be distributed to dental interns.<br>* Other names: KAP survey;|

Assessment of Knowledge, Attitude, and Practice of Minimal Intervention Dentistry in a Group of Dental Interns Study Overview ================= Brief Summary ----------------- Minimal intervention dentistry (MID) is a modern medical approach that aims to maximize preservation of healthy dental tissues. When operative intervention is required it is as minimally invasive as possible. This study will assess the knowledge of a group of dental interns regarding minimal intervention dentistry in Egypt and whether this knowledge is translated into positive attitude and practice among them. Detailed Description ----------------- Healthy oral tissues enable the child to eat, speak and socialize which contributes to general wellbeing. Dental caries during childhood is a major public health problem and throughout the 20th century, the dominant practice patterns of managing dental caries relied on the purely surgical approach of G.V Black such as the concept of extension for prevention. One of the drawbacks of this approach is an unnecessary removal of healthy oral tissues. Comprehensive knowledge of dental cariology, advances in dental restorative materials and modern diagnostic devices are changing pediatric restorative dentistry. minimal intervention dentistry (MID) is a modern medical approach that aims to maximize preservation of healthy dental tissues based on individualized patient care of early detection of disease, risk assessment diagnosis, and prevention. When operative intervention is required it is as minimally invasive as possible. There is insufficient information about knowledge and practice of modern dental approaches including minimal intervention dentistry among dental interns in Egypt. Available studies concerned with this subject were not done in Egypt. Due to this shortage of information, the application of MID in the Egyptian society cannot be fully assessed, and problems associated with its practice cannot be identified and solved. This shortage of information may also deprive children of getting benefits of MID. Thus; this study will assess the knowledge of a group of dental interns regarding minimal intervention dentistry in Egypt, and whether this knowledge is translated into positive attitude and practice among them. Knowledge, attitude, and practice (KAP) surveys can be used to identify knowledge gaps and culturally related misconceptions of new health approaches or interventions. They can determine factors influencing behaviors that are not known, and how and why people practice certain health behaviors. KAP surveys can be also used to identify needs, problems and barriers, as well as solutions for improving quality and accessibility of health services by studying factors and possible determinants influencing treatment decisions. This study aims to identify deficiencies (if present) in knowledge, attitude, and practice of MID among a group of dental interns in Egypt. Official Title ----------------- Assessment of Knowledge, Attitude, and Practice of Minimal Intervention Dentistry in a Group of Dental Interns in Egypt: A Cross-sectional Study Conditions ----------------- Pediatric Dentistry Intervention / Treatment ----------------- * Other: Knowledge, attitude, and practice survey Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Dental interns attending pediatric dentistry in the faculty of dentistry, Cairo University. Exclusion Criteria: Interns refusing to participate in the study. Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | dental interns<br>dental interns in pediatric dentistry department, faculty of dentistry, Cairo University. | Other: Knowledge, attitude, and practice survey<br>* A knowledge, attitude, and practice questionnaire is going to be distributed to dental interns.<br>* Other names: KAP survey;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Knowledge, attitude and practice mean score | Scores will be calculated according to the options selected by dental interns. The primary outcome is the mean score of the knowledge, attitude and practice survey. | Through study completion, an average of 1 year. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | response rate | percentage of dental interns who agree to participate in the study. | Through study completion, an average of 1 year. |

NCT00236730

A Study of the Efficacy and Safety of Topiramate in the Treatment of Patients With Difficult to Control Epilepsy

The purpose of the study is to evaluate the effectiveness and safety of topiramate as add-on therapy in patients with difficult to control partial onset seizures who are taking one or two standard anti-epileptic drugs.

Epilepsy is characterized by seizures, which are abnormal electrical discharges in the brain that temporarily disrupt normal brain function. Seizures are classified as generalized, originating in both sides of the brain simultaneously, or partial-onset, starting in one area of the brain. Antiepilepsy medications, such as topiramate, are selected based on seizure type. This is a double-blind, placebo-controlled study that includes a baseline phase and a treatment phase. During the baseline phase (12 weeks duration), patients receive one or two of the following standard antiepileptic drugs (AEDs): phenytoin, carbamazepine, phenobarbital, or primidone. Patients who continue to have seizures during treatment with standard AEDs proceed into the double-blind treatment phase. Patients then receive placebo or topiramate at a dosage of 100-milligrams (mg) once daily, increasing to twice daily dosing at a maximum dose of 200 mg/day, 400 mg/day, or 600 mg/day or maximum tolerated dose (depending on treatment group), through Week 16 (total duration of double-blind phase), while continuing on their standard AED regimen. Assessments of effectiveness include the percent reduction in the average monthly seizure rate, percent of patients responding to treatment (having equal to or greater than 50% reduction in seizure rate), and, the patient's and investigator's global assessments of medication at end of study. Safety assessments include the incidence of adverse events throughout the study, clinical laboratory tests (hematology, serum chemistry, urinalysis), neurologic examinations, and vital sign measurements (blood pressure, pulse, temperature) weekly during the treatment phase. The study hypothesis is that topiramate, taken as add-on therapy to treatment with AEDs, will significantly reduce seizure frequency, compared with placebo, in patients with refractory partial epilepsy and is well-tolerated. Topiramate, 100 milligrams[mg] oral tablets. Dosage begins at 100-mg once daily and increases gradually to twice daily dosing at a maximum dose of 200, 400, or 600 mg/day, and continues through Week 16 (total duration).

Double-Blind Parallel Comparison of Three Doses of Topiramate and Placebo in Refractory Partial Epilepsy

Epilepsy, Epilepsies, Partial, Seizures

* Drug: topiramate

Inclusion Criteria:~History of simple or complex partial epilepsy that has been documented or witnessed~during a 12-week baseline phase, patient must have at least 12 partial seizures while maintaining therapeutic levels of antiepileptic drugs (AEDs)~and have no more than one seizure-free interval of up to 3 weeks and none longer than 3 weeks~good physical health.~Exclusion Criteria:~Patients having solely generalized seizures or lacking documentation of partial epilepsy~patients with generalized tonic-clonic seizures or other generalized epilepsies in the absence of an EEG consistent with partial epilepsy~generalized seizures, which are defined by the EEG wave pattern~seizures that lack an abnormal pulsation pattern on EEG~females who are capable of having children

18 Years

65 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percent reduction in the average monthly seizure rate from baseline to end of treatment | | |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percent of patients responding to treatment (>= 50% reduction in seizure rate from baseline to end of treatment); patient's and investigator's global assessments at end of study; incidence of adverse events throughout study | | |

topiramate, epilepsy, partial epilepsies, partial epilepsy, seizures, epileptic seizures, partial seizure disorder, brain diseases

Topiramate, Anticonvulsants, Hypoglycemic Agents, Physiological Effects of Drugs

| Intervention/Treatment | | --- | |Drug: topiramate|nan|

A Study of the Efficacy and Safety of Topiramate in the Treatment of Patients With Difficult to Control Epilepsy Study Overview ================= Brief Summary ----------------- The purpose of the study is to evaluate the effectiveness and safety of topiramate as add-on therapy in patients with difficult to control partial onset seizures who are taking one or two standard anti-epileptic drugs. Detailed Description ----------------- Epilepsy is characterized by seizures, which are abnormal electrical discharges in the brain that temporarily disrupt normal brain function. Seizures are classified as generalized, originating in both sides of the brain simultaneously, or partial-onset, starting in one area of the brain. Antiepilepsy medications, such as topiramate, are selected based on seizure type. This is a double-blind, placebo-controlled study that includes a baseline phase and a treatment phase. During the baseline phase (12 weeks duration), patients receive one or two of the following standard antiepileptic drugs (AEDs): phenytoin, carbamazepine, phenobarbital, or primidone. Patients who continue to have seizures during treatment with standard AEDs proceed into the double-blind treatment phase. Patients then receive placebo or topiramate at a dosage of 100-milligrams (mg) once daily, increasing to twice daily dosing at a maximum dose of 200 mg/day, 400 mg/day, or 600 mg/day or maximum tolerated dose (depending on treatment group), through Week 16 (total duration of double-blind phase), while continuing on their standard AED regimen. Assessments of effectiveness include the percent reduction in the average monthly seizure rate, percent of patients responding to treatment (having equal to or greater than 50% reduction in seizure rate), and, the patient's and investigator's global assessments of medication at end of study. Safety assessments include the incidence of adverse events throughout the study, clinical laboratory tests (hematology, serum chemistry, urinalysis), neurologic examinations, and vital sign measurements (blood pressure, pulse, temperature) weekly during the treatment phase. The study hypothesis is that topiramate, taken as add-on therapy to treatment with AEDs, will significantly reduce seizure frequency, compared with placebo, in patients with refractory partial epilepsy and is well-tolerated. Topiramate, 100 milligrams[mg] oral tablets. Dosage begins at 100-mg once daily and increases gradually to twice daily dosing at a maximum dose of 200, 400, or 600 mg/day, and continues through Week 16 (total duration). Official Title ----------------- Double-Blind Parallel Comparison of Three Doses of Topiramate and Placebo in Refractory Partial Epilepsy Conditions ----------------- Epilepsy, Epilepsies, Partial, Seizures Intervention / Treatment ----------------- * Drug: topiramate Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: History of simple or complex partial epilepsy that has been documented or witnessed during a 12-week baseline phase, patient must have at least 12 partial seizures while maintaining therapeutic levels of antiepileptic drugs (AEDs) and have no more than one seizure-free interval of up to 3 weeks and none longer than 3 weeks good physical health. Exclusion Criteria: Patients having solely generalized seizures or lacking documentation of partial epilepsy patients with generalized tonic-clonic seizures or other generalized epilepsies in the absence of an EEG consistent with partial epilepsy generalized seizures, which are defined by the EEG wave pattern seizures that lack an abnormal pulsation pattern on EEG females who are capable of having children Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Intervention/Treatment | | --- | |Drug: topiramate|nan| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percent reduction in the average monthly seizure rate from baseline to end of treatment | | | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percent of patients responding to treatment (>= 50% reduction in seizure rate from baseline to end of treatment); patient's and investigator's global assessments at end of study; incidence of adverse events throughout study | | | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- topiramate, epilepsy, partial epilepsies, partial epilepsy, seizures, epileptic seizures, partial seizure disorder, brain diseases

NCT00270127

Epoetin Alfa for Anemia in Patients With Cancer Receiving Non-platinum Chemotherapy

The purpose of this study is to evaluate the effectiveness of epoetin alfa versus placebo in reducing or preventing the need for transfusions in anemic patients with non-myeloid cancer on non-platinum chemotherapy, and to investigate quality-of-life benefits associated with the use of epoetin alfa. Epoetin alfa is a genetically engineered protein that stimulates red blood cell production.

Cancer patients often experience anemia due to the disease itself, chemotherapy, or both. Quality of life is also affected, due in part to the fatigue associated with anemia. Previous studies with epoetin alfa have suggested that achieving a higher hemoglobin level may improve quality of life and help patients live longer. This is a randomized, double-blind, placebo-controlled, multicenter study to assess the effect of treatment with epoetin alfa in reducing or preventing anemia and transfusions in patients receiving non-platinum chemotherapy for non-myeloid cancers. The study also aims to determine whether changes in erythropoietin and hemoglobin levels after 2 weeks, serum ferritin (iron) levels after 2 weeks and changes in hemoglobin and developing red blood cells after either 2 or 4 weeks predict responsiveness to epoetin alfa. There will be 2 treatment groups: one group will receive subcutaneous epoetin alfa injections 3 times per week (starting at 150 units per kilogram, adjusted if needed to a maximum of 300 units per kilogram) and the other group will receive an equal volume of matching subcutaneous placebo. Treatment is to continue for 12 to 24 weeks (3 to 6 chemotherapy cycles), plus 4 weeks post-chemotherapy. Patients in the study will be observed a year after the study ends for survival data. The primary measure of effectiveness will be determined by the number of patients who are transfused, depending on primary tumor type (solid or blood) and level of hemoglobin (above or below 10.5 grams per deciliter). Additional measures of effectiveness include the change in hemoglobin, hematocrit, and developing red blood cells from the start of the study until study completion, and the change in quality of life. Safety evaluations (incidence and severity of adverse events, laboratory tests, vital signs and physical examinations) will be performed throughout the study. The hypothesis of the study is that epoetin alfa will be superior to placebo in reducing the need for transfusions and in improving anemia and quality of life. 150 units per kilogram of epoetin alfa (or placebo) 3 times weekly subcutaneously for 4 weeks, then continuing this dose or 300 units per kilogram, depending on developing red blood cell counts and/or hemoglobin. Study duration is 12 to 24 weeks (3 to 6 cycles) plus 4 weeks post-chemotherapy.

Double-Blind, Placebo-Controlled Study to Assess the Effect of Early Intervention and/or Treatment With Epoetin Alfa on Anemia in Cancer Patients Receiving Non-Platinum-Containing Chemotherapy

Anemia, Cancer, Neoplasm

* Drug: Epoetin alfa

Inclusion Criteria:~Confirmed diagnosis of non-myeloid malignancy~undergoing treatment with non-platinum-containing chemotherapy, or non-platinum-containing chemotherapy is imminent~Eastern Cooperative Oncology Group (which is a scale used by researchers to represent the level of activity that a patient is capable of) score of 0 (fully active, no disease restriction) to 3 (capable of only limited self-care, confined to bed or chair more than 50% of waking hours)~life expectancy of at least 6 months~baseline hemoglobin <= 10.5 grams per deciliter (or a fall in hemoglobin level >= 1.5 grams per deciliter per cycle or per month since the beginning of the current course of chemotherapy such that it dropped to <= 12 grams per deciliter) and baseline count of <125,000 microliters for developing red cells~Exclusion Criteria:~Patients having a clinically significant disease other than cancer~treated by platinum-containing chemotherapy within 3 months of study start~having uncontrolled high blood pressure, a history of seizure, or untreated iron, folate, or Vitamin B12 deficiency~received a transfusion or radiotherapy within 2 weeks of study start, or had surgery within 1 week of study start~intending to use steroid drugs during the study

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of patients transfused after one month | | |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in hemoglobin, hematocrit, and developing red blood cells from the start of the study until study completion; Changes in quality-of-life; Safety | | |

Anemia, cancer, quality of life, chemotherapy, hemoglobin, transfusion, epoetin alfa, epoetin, erythropoietin

Epoetin Alfa, Hematinics

| Intervention/Treatment | | --- | |Drug: Epoetin alfa|nan|

Epoetin Alfa for Anemia in Patients With Cancer Receiving Non-platinum Chemotherapy Study Overview ================= Brief Summary ----------------- The purpose of this study is to evaluate the effectiveness of epoetin alfa versus placebo in reducing or preventing the need for transfusions in anemic patients with non-myeloid cancer on non-platinum chemotherapy, and to investigate quality-of-life benefits associated with the use of epoetin alfa. Epoetin alfa is a genetically engineered protein that stimulates red blood cell production. Detailed Description ----------------- Cancer patients often experience anemia due to the disease itself, chemotherapy, or both. Quality of life is also affected, due in part to the fatigue associated with anemia. Previous studies with epoetin alfa have suggested that achieving a higher hemoglobin level may improve quality of life and help patients live longer. This is a randomized, double-blind, placebo-controlled, multicenter study to assess the effect of treatment with epoetin alfa in reducing or preventing anemia and transfusions in patients receiving non-platinum chemotherapy for non-myeloid cancers. The study also aims to determine whether changes in erythropoietin and hemoglobin levels after 2 weeks, serum ferritin (iron) levels after 2 weeks and changes in hemoglobin and developing red blood cells after either 2 or 4 weeks predict responsiveness to epoetin alfa. There will be 2 treatment groups: one group will receive subcutaneous epoetin alfa injections 3 times per week (starting at 150 units per kilogram, adjusted if needed to a maximum of 300 units per kilogram) and the other group will receive an equal volume of matching subcutaneous placebo. Treatment is to continue for 12 to 24 weeks (3 to 6 chemotherapy cycles), plus 4 weeks post-chemotherapy. Patients in the study will be observed a year after the study ends for survival data. The primary measure of effectiveness will be determined by the number of patients who are transfused, depending on primary tumor type (solid or blood) and level of hemoglobin (above or below 10.5 grams per deciliter). Additional measures of effectiveness include the change in hemoglobin, hematocrit, and developing red blood cells from the start of the study until study completion, and the change in quality of life. Safety evaluations (incidence and severity of adverse events, laboratory tests, vital signs and physical examinations) will be performed throughout the study. The hypothesis of the study is that epoetin alfa will be superior to placebo in reducing the need for transfusions and in improving anemia and quality of life. 150 units per kilogram of epoetin alfa (or placebo) 3 times weekly subcutaneously for 4 weeks, then continuing this dose or 300 units per kilogram, depending on developing red blood cell counts and/or hemoglobin. Study duration is 12 to 24 weeks (3 to 6 cycles) plus 4 weeks post-chemotherapy. Official Title ----------------- Double-Blind, Placebo-Controlled Study to Assess the Effect of Early Intervention and/or Treatment With Epoetin Alfa on Anemia in Cancer Patients Receiving Non-Platinum-Containing Chemotherapy Conditions ----------------- Anemia, Cancer, Neoplasm Intervention / Treatment ----------------- * Drug: Epoetin alfa Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Confirmed diagnosis of non-myeloid malignancy undergoing treatment with non-platinum-containing chemotherapy, or non-platinum-containing chemotherapy is imminent Eastern Cooperative Oncology Group (which is a scale used by researchers to represent the level of activity that a patient is capable of) score of 0 (fully active, no disease restriction) to 3 (capable of only limited self-care, confined to bed or chair more than 50% of waking hours) life expectancy of at least 6 months baseline hemoglobin <= 10.5 grams per deciliter (or a fall in hemoglobin level >= 1.5 grams per deciliter per cycle or per month since the beginning of the current course of chemotherapy such that it dropped to <= 12 grams per deciliter) and baseline count of <125,000 microliters for developing red cells Exclusion Criteria: Patients having a clinically significant disease other than cancer treated by platinum-containing chemotherapy within 3 months of study start having uncontrolled high blood pressure, a history of seizure, or untreated iron, folate, or Vitamin B12 deficiency received a transfusion or radiotherapy within 2 weeks of study start, or had surgery within 1 week of study start intending to use steroid drugs during the study Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Intervention/Treatment | | --- | |Drug: Epoetin alfa|nan| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of patients transfused after one month | | | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in hemoglobin, hematocrit, and developing red blood cells from the start of the study until study completion; Changes in quality-of-life; Safety | | | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Anemia, cancer, quality of life, chemotherapy, hemoglobin, transfusion, epoetin alfa, epoetin, erythropoietin

NCT00185991

Comparison of Once Daily Versus 8 Hour Dosing of Gentamicin for the Treatment of Intrapartum Chorioamnionitis

To compare once daily versus 8 hour dosing of gentamicin for the treatment of chorioamnionitis.

Comparison of Once Daily Versus 8 Hour Dosing of Gentamicin for the Treatment of Intrapartum Chorioamnionitis

Chorioamnionitis

* Drug: gentamicin

Inclusion Criteria:~- clinical diagnosis of chorioamnionitis~Exclusion Criteria:~- maternal renal disease, intrauterine fetal death, allergy to gentamicin

18 Years

Female

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Single Group Assignment Masking: Triple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Afebrile at 24 hours and no endometritis | | 24 hours after delivery |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Neonatal outcomes | | Time of delivery to time of discharge |

Gentamicins, Anti-Bacterial Agents, Anti-Infective Agents, Protein Synthesis Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Once daily Gentamicin<br> | Drug: gentamicin<br>* Daily gentamicin (5 mg/kg intravenously, then placebo doses IV after 8 and 16 hours).~Eight hour gentamicin (2 mg/kg intravenously, then 1.5 mg/kg IV after 8 and 16 hours).<br>| | Active Comparator: Every eight hour Gentamicin<br> | Drug: gentamicin<br>* Daily gentamicin (5 mg/kg intravenously, then placebo doses IV after 8 and 16 hours).~Eight hour gentamicin (2 mg/kg intravenously, then 1.5 mg/kg IV after 8 and 16 hours).<br>|

Comparison of Once Daily Versus 8 Hour Dosing of Gentamicin for the Treatment of Intrapartum Chorioamnionitis Study Overview ================= Brief Summary ----------------- To compare once daily versus 8 hour dosing of gentamicin for the treatment of chorioamnionitis. Official Title ----------------- Comparison of Once Daily Versus 8 Hour Dosing of Gentamicin for the Treatment of Intrapartum Chorioamnionitis Conditions ----------------- Chorioamnionitis Intervention / Treatment ----------------- * Drug: gentamicin Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: - clinical diagnosis of chorioamnionitis Exclusion Criteria: - maternal renal disease, intrauterine fetal death, allergy to gentamicin Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Single Group Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Once daily Gentamicin<br> | Drug: gentamicin<br>* Daily gentamicin (5 mg/kg intravenously, then placebo doses IV after 8 and 16 hours). Eight hour gentamicin (2 mg/kg intravenously, then 1.5 mg/kg IV after 8 and 16 hours).<br>| | Active Comparator: Every eight hour Gentamicin<br> | Drug: gentamicin<br>* Daily gentamicin (5 mg/kg intravenously, then placebo doses IV after 8 and 16 hours). Eight hour gentamicin (2 mg/kg intravenously, then 1.5 mg/kg IV after 8 and 16 hours).<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Afebrile at 24 hours and no endometritis | | 24 hours after delivery | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Neonatal outcomes | | Time of delivery to time of discharge |

NCT02876926

Evaluating a Real-Time, Remote Monitoring System for Home-Based HIV Testing

This study explores whether offering follow-up counseling and referral over the phone after using a home-based HIV test increases rates of ever and repeat testing, compared with home-based testing with no follow-up (HBST alone) or mailing reminders for clinic-based testing.

Exploring Use of a Real-time, Remote Monitoring and Follow-up System for Home-based, HIV Self-testing Among High-risk Men Who Have Sex With Men (MSM)

HIV

* Behavioral: Smart home-based test for HIV * Behavioral: Home-based testing only * Behavioral: Reminder letters for clinic-based testing

Inclusion Criteria:~Sex with a partner met online in the past year~Anal sex (either insertive or receptive) with a casual male partner in the past 6 months without using condoms or pre-exposure prophylaxis~Own a smartphone (iOS or Android) with a service contract and data plan~Have a stable address where mail can be received~Speak English fluently~Exclusion Criteria:~Having tested for HIV in the last year

18 Years

Male

Accepts Healthy Volunteers

Primary Purpose: Diagnostic Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants Who Received HIV Testing | Count of the number of participants who reported receiving HIV testing. | Up to 28 weeks | | Number of Participants Who Reported Having Been Referred for Pre-exposure Prophylaxis | Count of the number of participants who reported receiving a referral for pre-exposure prophylaxis from a counselor or medical professional. | Up to 28 weeks | | Number of Participants Who Reported Having Actually Received a Prescription for Pre-exposure Prophylaxis | Count of the number of participants who reported actually having received a prescription for pre-exposure prophylaxis after having been referred by a medical professional. | Up to 28 weeks |

HIV testing, Self-testing, Counseling, Referral

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Enhanced home-based testing<br>These participants will download a study-specific smartphone app (eTEST), and receive home-based HIV test kits in the mail every 3 months. These kits will have been fit with sensors that enable remote detection of when the kit was opened. Qualified HIV test counselors (QHTC) will then follow up with these participants within 24 hours of receiving notification that the test has been opened to conduct routine counseling, offer referrals for other services, and connect those with reactive results with follow-up care. | Behavioral: Smart home-based test for HIV<br>* A standard home-based HIV test kit, fit with a Bluetooth low energy beacon to allow remote monitoring.<br>| | Active Comparator: Home-based testing alone<br>These participants will receive a typical home-based test for HIV in the mail every 3 months, but no phone-based follow-up will be provided. | Behavioral: Home-based testing only<br>* A standard home-based HIV test kit.<br>| | Sham Comparator: Reminders for clinic-based testing<br>Participants in this condition will receive a letter in the mail every 3 months reminding them to be tested at a local clinic for free. | Behavioral: Reminder letters for clinic-based testing<br>* Letters reminding patients to get tested at a free clinic location<br>|

Evaluating a Real-Time, Remote Monitoring System for Home-Based HIV Testing Study Overview ================= Brief Summary ----------------- This study explores whether offering follow-up counseling and referral over the phone after using a home-based HIV test increases rates of ever and repeat testing, compared with home-based testing with no follow-up (HBST alone) or mailing reminders for clinic-based testing. Official Title ----------------- Exploring Use of a Real-time, Remote Monitoring and Follow-up System for Home-based, HIV Self-testing Among High-risk Men Who Have Sex With Men (MSM) Conditions ----------------- HIV Intervention / Treatment ----------------- * Behavioral: Smart home-based test for HIV * Behavioral: Home-based testing only * Behavioral: Reminder letters for clinic-based testing Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Sex with a partner met online in the past year Anal sex (either insertive or receptive) with a casual male partner in the past 6 months without using condoms or pre-exposure prophylaxis Own a smartphone (iOS or Android) with a service contract and data plan Have a stable address where mail can be received Speak English fluently Exclusion Criteria: Having tested for HIV in the last year Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Diagnostic Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Enhanced home-based testing<br>These participants will download a study-specific smartphone app (eTEST), and receive home-based HIV test kits in the mail every 3 months. These kits will have been fit with sensors that enable remote detection of when the kit was opened. Qualified HIV test counselors (QHTC) will then follow up with these participants within 24 hours of receiving notification that the test has been opened to conduct routine counseling, offer referrals for other services, and connect those with reactive results with follow-up care. | Behavioral: Smart home-based test for HIV<br>* A standard home-based HIV test kit, fit with a Bluetooth low energy beacon to allow remote monitoring.<br>| | Active Comparator: Home-based testing alone<br>These participants will receive a typical home-based test for HIV in the mail every 3 months, but no phone-based follow-up will be provided. | Behavioral: Home-based testing only<br>* A standard home-based HIV test kit.<br>| | Sham Comparator: Reminders for clinic-based testing<br>Participants in this condition will receive a letter in the mail every 3 months reminding them to be tested at a local clinic for free. | Behavioral: Reminder letters for clinic-based testing<br>* Letters reminding patients to get tested at a free clinic location<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants Who Received HIV Testing | Count of the number of participants who reported receiving HIV testing. | Up to 28 weeks | | Number of Participants Who Reported Having Been Referred for Pre-exposure Prophylaxis | Count of the number of participants who reported receiving a referral for pre-exposure prophylaxis from a counselor or medical professional. | Up to 28 weeks | | Number of Participants Who Reported Having Actually Received a Prescription for Pre-exposure Prophylaxis | Count of the number of participants who reported actually having received a prescription for pre-exposure prophylaxis after having been referred by a medical professional. | Up to 28 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- HIV testing, Self-testing, Counseling, Referral

NCT03644979

Skydiving as a Model of Psychological Stress and Its Effect on Intestinal Barrier Function

In this study, it will be investigated how psychological stress evoked by skydiving affects the intestinal permeability in 20 healthy subjects. Participants attend two visits: 1) Skydiving visit, 2) Negative control visit. At all visits, saliva samples, blood samples, and faecal samples are collected, and the multi-sugar permeability test is performed. In this test, participants drink a sugar solution and then collect urine for 5 and 24 h. The ratio of the sugars detected in the urine is a reflection of the intestinal permeability. Saliva samples are collected for assessment of cortisol, a stress marker. Blood and faecal samples are collected for assessment of markers of intestinal barrier function and inflammation.

Skydiving as a Model of Psychological Stress and Its Effect on Intestinal Barrier Function

Psychological Stress Due to Skydiving

* Other: Skydiving

Inclusion Criteria:~Written informed consent prior to any study related procedures~Age > 18 till <50~Novice skydivers (first or second tandem jump)~Signed up for tandem skydive~Willing to abstain from probiotic products or medications known to alter gastrointestinal function throughout the study~Exclusion Criteria:~Abdominal surgery which might influence gastrointestinal function, except appendectomy and cholecystectomy.~Current diagnosis of hypertension.~Current diagnosis of psychiatric disease.~Over 100kg or with a body mass index over 35.~Systemic use of steroids in the last 6 weeks.~Use of antibiotics or antimicrobial medication in the last month.~Daily usage of non-steroidal anti-inflammatory drugs in the last 2 months or incidental use in the last 2 weeks prior to screening.~Usage of medications that could affect the barrier function, except oral contraceptives, during the 14 days prior to screening.~Diagnosed inflammatory gastrointestinal disease.~Regular use of probiotics in the last 6 weeks.~Smoking and/or chewable tobacco.~Planned changes to current diet or exercise regime.~Use of laxatives, anti-diarrhetics, anti-cholinergics within last 4 weeks prior to screening.~Use of immunosuppressant drugs within last 4 weeks prior to screening.~Women: Pregnancy, lactation.~Abuse of alcohol or drugs.~Any disease/condition which in the investigator's opinion could interfere with the intestinal barrier function.~Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial.

18 Years

50 Years

All

Accepts Healthy Volunteers

Primary Purpose: Basic Science Allocation: Non-Randomized Intervention Model: Crossover Assignment Interventional Model Description: 1) Skydiving visit, 2) Negative control visit Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in small intestinal permeability after skydiving measured as the urinary lactulose/rhamnose secretion ratio compared to negative control | | 2-4 weeks |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in whole gut permeability after skydiving measured as the urinary sucralose/erythritol secretion ratio compared to negative control | | 2-4 weeks | | Change in colonic permeability after skydiving measured as the urinary sucralose/erythritol secretion ratio compared to negative control | | 2-4 weeks | | Change in gastroduodenal permeability after skydiving measured as urinary sucrose excretion | | 2-4 weeks | | Change in quantity of intestinal permeability markers in blood after skydiving compared to the negative control | fatty acid binding proteins, zonulin, claudin-3, 16S rRNA | 2-4 weeks | | Change in salivary cortisol levels after skydiving compared to the negative control | | 2-4 weeks |

Stress, Psychological, Behavioral Symptoms

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Skydiving<br>Tandem skydiving | Other: Skydiving<br>* Tandem skydiving (with an experienced instructor)<br>| | No Intervention: Negative control<br>No skydiving | |

Skydiving as a Model of Psychological Stress and Its Effect on Intestinal Barrier Function Study Overview ================= Brief Summary ----------------- In this study, it will be investigated how psychological stress evoked by skydiving affects the intestinal permeability in 20 healthy subjects. Participants attend two visits: 1) Skydiving visit, 2) Negative control visit. At all visits, saliva samples, blood samples, and faecal samples are collected, and the multi-sugar permeability test is performed. In this test, participants drink a sugar solution and then collect urine for 5 and 24 h. The ratio of the sugars detected in the urine is a reflection of the intestinal permeability. Saliva samples are collected for assessment of cortisol, a stress marker. Blood and faecal samples are collected for assessment of markers of intestinal barrier function and inflammation. Official Title ----------------- Skydiving as a Model of Psychological Stress and Its Effect on Intestinal Barrier Function Conditions ----------------- Psychological Stress Due to Skydiving Intervention / Treatment ----------------- * Other: Skydiving Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Written informed consent prior to any study related procedures Age > 18 till <50 Novice skydivers (first or second tandem jump) Signed up for tandem skydive Willing to abstain from probiotic products or medications known to alter gastrointestinal function throughout the study Exclusion Criteria: Abdominal surgery which might influence gastrointestinal function, except appendectomy and cholecystectomy. Current diagnosis of hypertension. Current diagnosis of psychiatric disease. Over 100kg or with a body mass index over 35. Systemic use of steroids in the last 6 weeks. Use of antibiotics or antimicrobial medication in the last month. Daily usage of non-steroidal anti-inflammatory drugs in the last 2 months or incidental use in the last 2 weeks prior to screening. Usage of medications that could affect the barrier function, except oral contraceptives, during the 14 days prior to screening. Diagnosed inflammatory gastrointestinal disease. Regular use of probiotics in the last 6 weeks. Smoking and/or chewable tobacco. Planned changes to current diet or exercise regime. Use of laxatives, anti-diarrhetics, anti-cholinergics within last 4 weeks prior to screening. Use of immunosuppressant drugs within last 4 weeks prior to screening. Women: Pregnancy, lactation. Abuse of alcohol or drugs. Any disease/condition which in the investigator's opinion could interfere with the intestinal barrier function. Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 50 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Non-Randomized Intervention Model: Crossover Assignment Interventional Model Description: 1) Skydiving visit, 2) Negative control visit Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Skydiving<br>Tandem skydiving | Other: Skydiving<br>* Tandem skydiving (with an experienced instructor)<br>| | No Intervention: Negative control<br>No skydiving | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in small intestinal permeability after skydiving measured as the urinary lactulose/rhamnose secretion ratio compared to negative control | | 2-4 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in whole gut permeability after skydiving measured as the urinary sucralose/erythritol secretion ratio compared to negative control | | 2-4 weeks | | Change in colonic permeability after skydiving measured as the urinary sucralose/erythritol secretion ratio compared to negative control | | 2-4 weeks | | Change in gastroduodenal permeability after skydiving measured as urinary sucrose excretion | | 2-4 weeks | | Change in quantity of intestinal permeability markers in blood after skydiving compared to the negative control | fatty acid binding proteins, zonulin, claudin-3, 16S rRNA | 2-4 weeks | | Change in salivary cortisol levels after skydiving compared to the negative control | | 2-4 weeks |

NCT02206698

Pediatric Blunt Abdominal Trauma Clinical Prediction Model

The submitted proposal is designed to reduce morbidity and mortality to injured children. Significant variability in the initial trauma assessment exists among institutions. The proposed project is a prospective, observational, multi-institutional study of children following blunt abdominal trauma. The specific goals of the project are to: 1) Document history, physical exam findings, imaging, and laboratory values, which are available to physicians during the initial trauma resuscitation prior to a decision on whether to order an abdominal computed tomography (CT) to evaluate for potential intra-abdominal injury; and 2) Derive and validate a multi-variable clinical prediction rule based on data variables readily available during the pediatric trauma resuscitation to identify patients at low risk for intra-abdominal injury, in which unnecessary CT might safely be avoided. Information from this study could be used to develop a more standardized approach to the evaluation for intra-abdominal injury following blunt trauma in children. This information could lead to significant improvement in the early recognition of injury and to improved resource utilization.

The proposed research project is a prospective, observational study. Data will be collected from each institution and entered into a secure REDCap database. Two phases of data collection will occur: 1) patient demographics and specific clinical variables which may be associated with IAI which are available and recorded during the initial trauma evaluation 2) laboratory and imaging results available after the initial assessment, identified injuries, patient disposition, interventions and outcomes.~Primary Outcome Variables: 1) Intra-abdominal injury (IAI) (presence of solid or hollow organ injury (spleen, liver, kidney, GI tract, adrenal, pancreas, intra-abdominal vascular structure, bladder, ureter, gallbladder, abdominal wall fascia)) 2) IAI requiring intervention (abdominal operation, angio-embolization, blood transfusion)~Time Course: The initial data collection period will extend for one year. Data will be recorded in a password protected redcap database which is readily available online to all participating institutions.~Study setting: Eleven Level One Pediatric Trauma Centers~Data collection points: demographics (age, mechanism, alert level), physical exam, labs (AST, HCT, amylase, UA, base deficit), FAST, imaging results, injuries, outcomes (admission, ICU admit, need for intervention, missed injuries, ISS).~Data Analysis: De-identified data will be used during the data analysis phase to minimize the risk of loss of confidentiality to the patients. Data analysis with development of a clinical prediction rule (CPM) will be performed as follows. A logistic regression will be used to fit a predictive model for both IAI and IAI requiring interventions. SAS 9.3 will be used for the statistical analysis. Validation (including sensitivity and negative predictive value) of the derived CPM would then be performed in a subsequent study using a second population of patients. Internal validation of the prediction model was assessed by creating a split sample using a random selection process; half of the sample was used as the initial cohort to develop the prediction model for estimates of all covariates, and the remaining half was used as the validation cohort to compare the true to the predicted outcomes. A receiver operating characteristic (ROC) curve is created by plotting sensitivity against (1- specificity) for different cut-off points of the predicted outcome. A bootstrap study of 1000 replications was performed on the level of sensitivity, specificity and TP/FP/FN/TN validation. Validation (including sensitivity and negative predictive value) of the derived CPM would then be performed in a subsequent study using a second population of patients.~Quality assurance plan: Data quality will be evaluated bi-monthly by a team consisting of the PI, an expert in clinical prediction models and a statistician. This panel will be able to review de-identified data from all institutions but will not have access to make any changes in the data entered in the centralized database.~Data checks to compare data entered into the registry against predefined rules for range or consistency: Data checks to compare entered registry data against predefined rules for range and consistency will be performed bi-monthly.~Source data verification: Source data collection is the responsibility of each individual institution. A data analysis team consisting of a statistician and an expert in clinical prediction models will evaluate the data bi-monthly to look for wide outliers (beyond pre-defined range) and impossible data values (not clinically possible) and request clarification from the individual institutions when necessary.~Data dictionary that contains detailed descriptions of each variable: The vast majority of the data collection points are discrete variables with no opportunity for free text data entry. Many of these variables are specifically described on the data collection tools. Data definitions and question from the individual sites are addressed in a frequently updated Frequently Asked Questions (FAQ) document which is sent out to the sites bi-monthly following data verification review.~Standard Operating Procedures to address registry operations and analysis activities: The database is established through a secure Vanderbilt Redcap web-based site. Individual site data collection will be analyzed and reviewed bi-monthly with feedback to each of the sites if data inconsistencies exist.~Plan for missing data to address situations where variables are reported as missing, unavailable, non-reported, cannot be interpreted, or considered missing because of data inconsistency or out-of-range results: Critical data which are missing, unavailable or not reported will not be utilized for the development of the blunt abdominal trauma clinical prediction model (BAT CPM). The investigators will attempt clarification for out of range results prior to data analysis. Variables which are available and reported in less than 50% of the patients will likely be excluded from the CPM because they will not form the basis of a practicable risk stratification model. The developed CPM will require validation in a second un-related population prior to widespread application of the CPM.

Multicenter, Prospective Development of a Clinical Prediction Model to Determine Which Children Can Safely Avoid Abdominal CT Scanning During the Initial Evaluation of Blunt Abdominal Trauma

Pediatric Abdominal Trauma

Inclusion Criteria:~Patients presenting as a Trauma system activation with suspicion for blunt abdominal trauma. (Fall >10 feet; Motor vehicle accident >40mph, pedestrian struck by auto, Motor vehicle crash with ejection or death in vehicle or rollover, assault, bicycle accident, ATV accident).~<16 years of age~The need to activate the trauma system is dictated by the Emergency Department physician~Consults called to the department of surgery for suspicion of intraabdominal traumatic injury~Exclusion Criteria:~16 years of age or older~Burn injury~Hanging~Drowning~Penetrating injury~CT A/P performed prior to arrival~Presentation >6 hours from time of injury~Pregnancy~Isolated head injury~Fall <10 feet with no concern for intraabdominal injury~Isolated extremity injury

15 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Intra-abdominal Injury (IAI) | Intra-abdominal injury (IAI) (presence of solid or hollow organ injury (spleen, liver, kidney, GI tract, adrenal, pancreas, intra-abdominal vascular structure, bladder, ureter, gallbladder, abdominal wall fascia)) | 30 days from time of trauma | | Intraabdominal Injury (IAI) requiring intervention | Intra-abdominal injury (IAI) requiring intervention (Laparoscopy or Laparotomy, angio-embolization, blood transfusion for IAI) | 30 days from time of trauma |

Pediatric trauma, Intraabdominal Injury, CT Abdomen and Pelvis, blunt abdominal injury, blunt trauma, clinical prediction model

Wounds and Injuries, Abdominal Injuries

Pediatric Blunt Abdominal Trauma Clinical Prediction Model Study Overview ================= Brief Summary ----------------- The submitted proposal is designed to reduce morbidity and mortality to injured children. Significant variability in the initial trauma assessment exists among institutions. The proposed project is a prospective, observational, multi-institutional study of children following blunt abdominal trauma. The specific goals of the project are to: 1) Document history, physical exam findings, imaging, and laboratory values, which are available to physicians during the initial trauma resuscitation prior to a decision on whether to order an abdominal computed tomography (CT) to evaluate for potential intra-abdominal injury; and 2) Derive and validate a multi-variable clinical prediction rule based on data variables readily available during the pediatric trauma resuscitation to identify patients at low risk for intra-abdominal injury, in which unnecessary CT might safely be avoided. Information from this study could be used to develop a more standardized approach to the evaluation for intra-abdominal injury following blunt trauma in children. This information could lead to significant improvement in the early recognition of injury and to improved resource utilization. Detailed Description ----------------- The proposed research project is a prospective, observational study. Data will be collected from each institution and entered into a secure REDCap database. Two phases of data collection will occur: 1) patient demographics and specific clinical variables which may be associated with IAI which are available and recorded during the initial trauma evaluation 2) laboratory and imaging results available after the initial assessment, identified injuries, patient disposition, interventions and outcomes. Primary Outcome Variables: 1) Intra-abdominal injury (IAI) (presence of solid or hollow organ injury (spleen, liver, kidney, GI tract, adrenal, pancreas, intra-abdominal vascular structure, bladder, ureter, gallbladder, abdominal wall fascia)) 2) IAI requiring intervention (abdominal operation, angio-embolization, blood transfusion) Time Course: The initial data collection period will extend for one year. Data will be recorded in a password protected redcap database which is readily available online to all participating institutions. Study setting: Eleven Level One Pediatric Trauma Centers Data collection points: demographics (age, mechanism, alert level), physical exam, labs (AST, HCT, amylase, UA, base deficit), FAST, imaging results, injuries, outcomes (admission, ICU admit, need for intervention, missed injuries, ISS). Data Analysis: De-identified data will be used during the data analysis phase to minimize the risk of loss of confidentiality to the patients. Data analysis with development of a clinical prediction rule (CPM) will be performed as follows. A logistic regression will be used to fit a predictive model for both IAI and IAI requiring interventions. SAS 9.3 will be used for the statistical analysis. Validation (including sensitivity and negative predictive value) of the derived CPM would then be performed in a subsequent study using a second population of patients. Internal validation of the prediction model was assessed by creating a split sample using a random selection process; half of the sample was used as the initial cohort to develop the prediction model for estimates of all covariates, and the remaining half was used as the validation cohort to compare the true to the predicted outcomes. A receiver operating characteristic (ROC) curve is created by plotting sensitivity against (1- specificity) for different cut-off points of the predicted outcome. A bootstrap study of 1000 replications was performed on the level of sensitivity, specificity and TP/FP/FN/TN validation. Validation (including sensitivity and negative predictive value) of the derived CPM would then be performed in a subsequent study using a second population of patients. Quality assurance plan: Data quality will be evaluated bi-monthly by a team consisting of the PI, an expert in clinical prediction models and a statistician. This panel will be able to review de-identified data from all institutions but will not have access to make any changes in the data entered in the centralized database. Data checks to compare data entered into the registry against predefined rules for range or consistency: Data checks to compare entered registry data against predefined rules for range and consistency will be performed bi-monthly. Source data verification: Source data collection is the responsibility of each individual institution. A data analysis team consisting of a statistician and an expert in clinical prediction models will evaluate the data bi-monthly to look for wide outliers (beyond pre-defined range) and impossible data values (not clinically possible) and request clarification from the individual institutions when necessary. Data dictionary that contains detailed descriptions of each variable: The vast majority of the data collection points are discrete variables with no opportunity for free text data entry. Many of these variables are specifically described on the data collection tools. Data definitions and question from the individual sites are addressed in a frequently updated Frequently Asked Questions (FAQ) document which is sent out to the sites bi-monthly following data verification review. Standard Operating Procedures to address registry operations and analysis activities: The database is established through a secure Vanderbilt Redcap web-based site. Individual site data collection will be analyzed and reviewed bi-monthly with feedback to each of the sites if data inconsistencies exist. Plan for missing data to address situations where variables are reported as missing, unavailable, non-reported, cannot be interpreted, or considered missing because of data inconsistency or out-of-range results: Critical data which are missing, unavailable or not reported will not be utilized for the development of the blunt abdominal trauma clinical prediction model (BAT CPM). The investigators will attempt clarification for out of range results prior to data analysis. Variables which are available and reported in less than 50% of the patients will likely be excluded from the CPM because they will not form the basis of a practicable risk stratification model. The developed CPM will require validation in a second un-related population prior to widespread application of the CPM. Official Title ----------------- Multicenter, Prospective Development of a Clinical Prediction Model to Determine Which Children Can Safely Avoid Abdominal CT Scanning During the Initial Evaluation of Blunt Abdominal Trauma Conditions ----------------- Pediatric Abdominal Trauma Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients presenting as a Trauma system activation with suspicion for blunt abdominal trauma. (Fall >10 feet; Motor vehicle accident >40mph, pedestrian struck by auto, Motor vehicle crash with ejection or death in vehicle or rollover, assault, bicycle accident, ATV accident). <16 years of age The need to activate the trauma system is dictated by the Emergency Department physician Consults called to the department of surgery for suspicion of intraabdominal traumatic injury Exclusion Criteria: 16 years of age or older Burn injury Hanging Drowning Penetrating injury CT A/P performed prior to arrival Presentation >6 hours from time of injury Pregnancy Isolated head injury Fall <10 feet with no concern for intraabdominal injury Isolated extremity injury Ages Eligible for Study ----------------- Maximum Age: 15 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Intra-abdominal Injury (IAI) | Intra-abdominal injury (IAI) (presence of solid or hollow organ injury (spleen, liver, kidney, GI tract, adrenal, pancreas, intra-abdominal vascular structure, bladder, ureter, gallbladder, abdominal wall fascia)) | 30 days from time of trauma | | Intraabdominal Injury (IAI) requiring intervention | Intra-abdominal injury (IAI) requiring intervention (Laparoscopy or Laparotomy, angio-embolization, blood transfusion for IAI) | 30 days from time of trauma | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Pediatric trauma, Intraabdominal Injury, CT Abdomen and Pelvis, blunt abdominal injury, blunt trauma, clinical prediction model

NCT05141552

The Safety of Dapagliflozin in Hemodialysis Patients With Heart Failure

SGLT2 inhibitor is a new type of sugar-lowering medicine and is recommended to treat heart failure. eGFR lower than 30ml/min/1.73M2 is contraindication of SGLT2 inhibitor. Heart failure is one of the most frequency CVD events for hemodialysis patients. But hemodialysis patient is unable to be treated with SGLT2 inhibitors as the contraindication. However, solute and fluid clearance are dependent on dialysis, but not renal function in hemodialysis patients. There is no data of SGLT2 inhibitor on hemodialysis patients. The aim of the present study is evaluate the safety of Dapagliflozin in hemodialysis patients with heart failure.~This is a randomized, control, open study. 20 hemodialysis patients with heart failure will be recruited. 10 of 20 subjects will be treated with dapagliflozin 10mg everyday for 12 weeks. The primary outcome is the number of patients with hypoglycemia or urinary infection. The secondary outcomes is the changes of NT-.

Evaluate the safety of dapagliflozin in hemodialysis patients with heart failure is the main purpose of this study. and Estimate the change of NT-proBNP is the secondary purpose.~This is a randomized, control and open study.~The including criteria are 1. Understand the present study and sign informed consert 2. Age is between 18 and 70 3. 2 or 3 times blood purification treatments (inclusion hemodialysis, hemofiltration, hemoperfusion) every week, 4. Blood purification treatment more than 3 month 5. Using AV fistula or artificial vascular access 6. With chronic heart failure (NYHC II-IV), and NT-proBNP>11500 or BNP>500 7. ARNI or RAS inhibitor or Aldosterone inhibitors treatment for at least 4 weeks with a stable dose The exclusion criteria are 1.Blood purification less than 3 month 2.With fluid overload and URR<50% 3.Have severe hypoglycemia (more than 2 events with 4 weeks prior to sign concert information) 4.Have severe hypotension (blood pressure <90/60mmHg more than 3 times with 4 weeks prior to sign concert information) 5.Have acute pulmonary edema 6.Have ketoacidosis 7.Have active pyelnephritis and symptomatic lower urinary infection 8.Subject is pregnant , is breast feeding 9.Subject has known SGLT2 inhibitor allergy or intolerance adverse reactions 10.Subject is currentluy enrolled in or has not yet completed at least 30days since ending other investigational device or drug trials 11.Investigator believe subject is not suitable for this study~Subjects will divide into two groups. Dapa group will be treated with dapagliflozin 10mg qd and standard anti-heart failure therapy. Control group will be treated with standard anti-heart failure therapy.~The primary outcome is the number of patients with hypoglycemia or urinary tract infection. The secondary outcome is the change of NT-proBNP

The Safety of Dapagliflozin in Hemodialysis Patients With Heart Failure

Hemodialysis Complication

* Drug: Dapagliflozin 10Mg Tab

Inclusion Criteria:~Understand the present studyAgree and sign informed consert~Age is between 18 and 70 Men or women ≧18 years and <70 years of age at screening~Treated with maintenance blood purification 2 or 3 times blood purification treatments (including hemodialysis, hemofiltration, hemoperfusion) every week2 or 3 times a week,~Blood purification treatment more than 3 month before randomization~Blood purification by uUsing AV fistula or artificial vascular access~DiagnosisWith chronic heart failure (NYHC II-IV), and NT-proBNP>11500 or BNP>500~ARNI or RAS inhibitor or Aldosterone inhibitors or beta receptor blocker treatment for at least 4 weeks with a stable dose.~Exclusion Criteria:~Blood purification less than 3 month~With fluid overload and URR<50%~Have severe hypoglycemia (more than 2 events with 4 weeks prior to sign concert information)~Have severe hypotension (blood pressure <90/60mmHg more than 3 times with 4 weeks prior to sign concert information)~Have acute pulmonary edema~Have ketoacidosis~Have active pyelnephritis and symptomatic lower urinary infection~Subject is pregnant , is breast feeding~Subject has known SGLT2 inhibitor allergy or intolerance adverse reactions~Subject is currentluy enrolled in or has not yet completed at least 30days since ending other investigational device or drug trials~Investigator believe subject is not suitable for this study

18 Years

70 Years

All

No

Primary Purpose: Other Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | the number of patients with hypoglycemia or urinary tract infection | the number of patients with hypoglycemia or urinary tract infection | 12 weeks |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change of NT-proBNP | Change of NT-proBNP | 12 weeks |

Dapagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Molecular Mechanisms of Pharmacological Action, Hypoglycemic Agents, Physiological Effects of Drugs

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: dapa group<br>subjects will be treated with dapagliflozin (10mg per day) and standard anti-heart failure therapy (including RAS inhibitors, beta-blocker, Aldosterone inhibitors) | Drug: Dapagliflozin 10Mg Tab<br>* In both group, subjects keep blood purification and anti heart failure treatment, including ARNI, RASi, Aldosterone inhibitors and beta receptor blocker.<br>* Other names: Control;| | No Intervention: control group<br>subjects will be treated with standard anti-heart failure therapy (including RAS inhibitors, beta-blocker, Aldosterone inhibitors) | |

The Safety of Dapagliflozin in Hemodialysis Patients With Heart Failure Study Overview ================= Brief Summary ----------------- SGLT2 inhibitor is a new type of sugar-lowering medicine and is recommended to treat heart failure. eGFR lower than 30ml/min/1.73M2 is contraindication of SGLT2 inhibitor. Heart failure is one of the most frequency CVD events for hemodialysis patients. But hemodialysis patient is unable to be treated with SGLT2 inhibitors as the contraindication. However, solute and fluid clearance are dependent on dialysis, but not renal function in hemodialysis patients. There is no data of SGLT2 inhibitor on hemodialysis patients. The aim of the present study is evaluate the safety of Dapagliflozin in hemodialysis patients with heart failure. This is a randomized, control, open study. 20 hemodialysis patients with heart failure will be recruited. 10 of 20 subjects will be treated with dapagliflozin 10mg everyday for 12 weeks. The primary outcome is the number of patients with hypoglycemia or urinary infection. The secondary outcomes is the changes of NT-. Detailed Description ----------------- Evaluate the safety of dapagliflozin in hemodialysis patients with heart failure is the main purpose of this study. and Estimate the change of NT-proBNP is the secondary purpose. This is a randomized, control and open study. The including criteria are 1. Understand the present study and sign informed consert 2. Age is between 18 and 70 3. 2 or 3 times blood purification treatments (inclusion hemodialysis, hemofiltration, hemoperfusion) every week, 4. Blood purification treatment more than 3 month 5. Using AV fistula or artificial vascular access 6. With chronic heart failure (NYHC II-IV), and NT-proBNP>11500 or BNP>500 7. ARNI or RAS inhibitor or Aldosterone inhibitors treatment for at least 4 weeks with a stable dose The exclusion criteria are 1.Blood purification less than 3 month 2.With fluid overload and URR<50% 3.Have severe hypoglycemia (more than 2 events with 4 weeks prior to sign concert information) 4.Have severe hypotension (blood pressure <90/60mmHg more than 3 times with 4 weeks prior to sign concert information) 5.Have acute pulmonary edema 6.Have ketoacidosis 7.Have active pyelnephritis and symptomatic lower urinary infection 8.Subject is pregnant , is breast feeding 9.Subject has known SGLT2 inhibitor allergy or intolerance adverse reactions 10.Subject is currentluy enrolled in or has not yet completed at least 30days since ending other investigational device or drug trials 11.Investigator believe subject is not suitable for this study Subjects will divide into two groups. Dapa group will be treated with dapagliflozin 10mg qd and standard anti-heart failure therapy. Control group will be treated with standard anti-heart failure therapy. The primary outcome is the number of patients with hypoglycemia or urinary tract infection. The secondary outcome is the change of NT-proBNP Official Title ----------------- The Safety of Dapagliflozin in Hemodialysis Patients With Heart Failure Conditions ----------------- Hemodialysis Complication Intervention / Treatment ----------------- * Drug: Dapagliflozin 10Mg Tab Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Understand the present studyAgree and sign informed consert Age is between 18 and 70 Men or women ≧18 years and <70 years of age at screening Treated with maintenance blood purification 2 or 3 times blood purification treatments (including hemodialysis, hemofiltration, hemoperfusion) every week2 or 3 times a week, Blood purification treatment more than 3 month before randomization Blood purification by uUsing AV fistula or artificial vascular access DiagnosisWith chronic heart failure (NYHC II-IV), and NT-proBNP>11500 or BNP>500 ARNI or RAS inhibitor or Aldosterone inhibitors or beta receptor blocker treatment for at least 4 weeks with a stable dose. Exclusion Criteria: Blood purification less than 3 month With fluid overload and URR<50% Have severe hypoglycemia (more than 2 events with 4 weeks prior to sign concert information) Have severe hypotension (blood pressure <90/60mmHg more than 3 times with 4 weeks prior to sign concert information) Have acute pulmonary edema Have ketoacidosis Have active pyelnephritis and symptomatic lower urinary infection Subject is pregnant , is breast feeding Subject has known SGLT2 inhibitor allergy or intolerance adverse reactions Subject is currentluy enrolled in or has not yet completed at least 30days since ending other investigational device or drug trials Investigator believe subject is not suitable for this study Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 70 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Other Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: dapa group<br>subjects will be treated with dapagliflozin (10mg per day) and standard anti-heart failure therapy (including RAS inhibitors, beta-blocker, Aldosterone inhibitors) | Drug: Dapagliflozin 10Mg Tab<br>* In both group, subjects keep blood purification and anti heart failure treatment, including ARNI, RASi, Aldosterone inhibitors and beta receptor blocker.<br>* Other names: Control;| | No Intervention: control group<br>subjects will be treated with standard anti-heart failure therapy (including RAS inhibitors, beta-blocker, Aldosterone inhibitors) | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | the number of patients with hypoglycemia or urinary tract infection | the number of patients with hypoglycemia or urinary tract infection | 12 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change of NT-proBNP | Change of NT-proBNP | 12 weeks |

NCT03147001

Protein Ingestion Before Training Low

A randomized interventions study using a crossover design. Ten well trained triathletes or bikeriders will be included for to undergo two trail separated by about 3 weeks. The night before the trail each subject will performe a high intense interval trainings session on an ergometer bike. during the night an infusion of aminoacid tracers will be initiated. The subject is woken at 6.30 a.m. Blood samples and a musclebiopsy will be collected prior to the morning bike ride at 8.00a.m. Immediately before the morning bike ride is started the subject will ingest a drink of 0,5g protein or a non-caloric placebo (random order). During the bike ride and the following 4,5 hours blood will be drawn with regular intervals. at time point 0, 60 and 180 min after the training session biopsies are collected.

Nutritional Strategies for Optimizing Adaptations and Recovery Following Training 'Low'.

Protein Metabolism

* Other: Protein ingestion * Other: Non-caloric placebo ingestion

Inclusion Criteria:~Healthy well-trained triathletes or cyclists~VO2max > 55 ml O2/kg/min~Training and has been training more than 7 times a week the last 6 months.~Exclusion Criteria:~VO2max < 55 ml O2/kg/min~Has chronic disease~has incjected with tracer on a previous occasion.

18 Years

50 Years

Male

Accepts Healthy Volunteers

Primary Purpose: Health Services Research Allocation: Randomized Intervention Model: Crossover Assignment Masking: Single

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Muscle protein fractional synthetic rate (FSR) | | FSR was measure over at time period of six hours |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Tracer kinetics dilution model | A-V tracer dilution model was applied across the forearm. | six hours | | Muscle signalling | Muscle signalling will be determined using western blotting in each muscle biopsy | Determined in biopsies sampled before and immediatly after 90min exercise in addition to one and four hours after exercise. | | Nitrogen excretion | nitrogen excretion is determined by Plasma and urinary carbide analysis as well as plasma NH4+. | Urine is collected during two periods. Collection period one: 12 hours prior to morning exercise. Collection period 2: During and four hours following exercise. Blood samples is drawn repeatedly from before to four hours after exercise. |

Dietary protein, Endurance exercise

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Protein ingestion<br>Subjects ingested protein drinks | Other: Protein ingestion<br>* A protein drink was ingested prior to the 90min bike ride in one of the completed trails (order randomised).<br>| | Placebo Comparator: Placebo<br>Subjects ingested a non-caloric placebo drink | Other: Non-caloric placebo ingestion<br>* A placebo drink was ingested prior to the 90min bike ride in one of the completed trails (order randomised).<br>|

Protein Ingestion Before Training Low Study Overview ================= Brief Summary ----------------- A randomized interventions study using a crossover design. Ten well trained triathletes or bikeriders will be included for to undergo two trail separated by about 3 weeks. The night before the trail each subject will performe a high intense interval trainings session on an ergometer bike. during the night an infusion of aminoacid tracers will be initiated. The subject is woken at 6.30 a.m. Blood samples and a musclebiopsy will be collected prior to the morning bike ride at 8.00a.m. Immediately before the morning bike ride is started the subject will ingest a drink of 0,5g protein or a non-caloric placebo (random order). During the bike ride and the following 4,5 hours blood will be drawn with regular intervals. at time point 0, 60 and 180 min after the training session biopsies are collected. Official Title ----------------- Nutritional Strategies for Optimizing Adaptations and Recovery Following Training 'Low'. Conditions ----------------- Protein Metabolism Intervention / Treatment ----------------- * Other: Protein ingestion * Other: Non-caloric placebo ingestion Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Healthy well-trained triathletes or cyclists VO2max > 55 ml O2/kg/min Training and has been training more than 7 times a week the last 6 months. Exclusion Criteria: VO2max < 55 ml O2/kg/min Has chronic disease has incjected with tracer on a previous occasion. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 50 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Health Services Research Allocation: Randomized Intervention Model: Crossover Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Protein ingestion<br>Subjects ingested protein drinks | Other: Protein ingestion<br>* A protein drink was ingested prior to the 90min bike ride in one of the completed trails (order randomised).<br>| | Placebo Comparator: Placebo<br>Subjects ingested a non-caloric placebo drink | Other: Non-caloric placebo ingestion<br>* A placebo drink was ingested prior to the 90min bike ride in one of the completed trails (order randomised).<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Muscle protein fractional synthetic rate (FSR) | | FSR was measure over at time period of six hours | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Tracer kinetics dilution model | A-V tracer dilution model was applied across the forearm. | six hours | | Muscle signalling | Muscle signalling will be determined using western blotting in each muscle biopsy | Determined in biopsies sampled before and immediatly after 90min exercise in addition to one and four hours after exercise. | | Nitrogen excretion | nitrogen excretion is determined by Plasma and urinary carbide analysis as well as plasma NH4+. | Urine is collected during two periods. Collection period one: 12 hours prior to morning exercise. Collection period 2: During and four hours following exercise. Blood samples is drawn repeatedly from before to four hours after exercise. | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Dietary protein, Endurance exercise

NCT02612142

Physical EXercise as an Adjunct Treatment for Depression

35 participants diagnosed with major depressive disorder were randomized in 3 intervention groups: (1) aerobic exercise (AE) ; (2) placebo (stretching) exercise (ST); and (3) no intervention (control group; NI). The intervention length was 10 consecutive days. In groups 1 (aerobic exercise) and 2 (sham exercise), participants exercised for 30 minutes each day. Depressive symptoms were assessed the day before the beginning of intervention and the day after the end of intervention for participants of both groups.

In the aerobic exercise (AE) group, the intervention consisted of 30 minutes of daily brisk walking or jogging. This was done individually and supervised. Participants who missed > 2 training sessions were considered as non-completers. Exercise intensity had to be maintained within 65%-75% of age-predicted maximal heart rate, as commonly prescribed in studies using aerobic exercise to alleviate depression. Heart rate monitoring devices were used.~Participants in the stretching (ST) group also performed a daily 30 minutes exercise program but this was sham exercise, consisting of stretching exercises. Several muscle groups (thighs, calves, gluteal, shoulders, back) were stretched for 60 seconds, with equivalent resting intervals between stretching series. These activities were also individual and supervised. As was the case for the AE intervention, participants who missed > 2 training sessions were considered as non-completers.~Participants in the control (NI) group received no intervention other than prescribed medication.~All participants started antidepressants within less than 2 weeks before study entry.

Efficacy of Exercise as an Adjunct Treatment for Clinically Depressed Inpatients During the Initial Stages of Antidepressant Therapy.

Major Depressive Disorder

* Behavioral: physical exercise

Inclusion Criteria:~diagnosis of major depressive disorder (MDD)~antidepressant drug therapy initiated for less than 2 weeks~score of 29 or more on the Beck depression inventory~Exclusion Criteria:~medical contraindication for exercise practice~inability to understand written French~beta-blocking drugs or another forms of antidepressant therapy (sleep deprivation, electroconvulsive therapy)

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Score change on the 21-item Beck depression inventory (BDI-II). Each item has a set of severity-graded self-evaluative statements that are rated 0 (neutral) to 3 (maximum severity). | | Baseline and 10 days |

Depressive Disorder, Depressive Disorder, Major, Mood Disorders, Mental Disorders

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: aerobic exercise (AE)<br>Intervention type: Behavioral. Intervention name: Aerobic exercise Intervention description: 10 days of daily aerobic exercise (brisk walking, jogging); duration: 30 minutes per session; intensity: 65%-75% of age-predicted maximal heart rate. All participants were treated with either paroxetine (20-50mg/day), fluoxetine (20-80mg/day) or bupropion (100-200mg/day). | Behavioral: physical exercise<br>* endurance-training or stretching (sham exercise)<br>| | Sham Comparator: stretching exercise (ST)<br>Intervention type: Behavioral. Intervention name: Stretching exercise Intervention description: 10 days of daily stretching exercise; duration: 30 minutes per session. All participants were treated with either paroxetine (20-50mg/day), fluoxetine (20-80mg/day) or bupropion (100-200mg/day). | Behavioral: physical exercise<br>* endurance-training or stretching (sham exercise)<br>| | No Intervention: no intervention (NI)<br>No behavioral intervention. All participants were treated with either paroxetine (20-50mg/day), fluoxetine (20-80mg/day) or bupropion (100-200mg/day). | |

Physical EXercise as an Adjunct Treatment for Depression Study Overview ================= Brief Summary ----------------- 35 participants diagnosed with major depressive disorder were randomized in 3 intervention groups: (1) aerobic exercise (AE) ; (2) placebo (stretching) exercise (ST); and (3) no intervention (control group; NI). The intervention length was 10 consecutive days. In groups 1 (aerobic exercise) and 2 (sham exercise), participants exercised for 30 minutes each day. Depressive symptoms were assessed the day before the beginning of intervention and the day after the end of intervention for participants of both groups. Detailed Description ----------------- In the aerobic exercise (AE) group, the intervention consisted of 30 minutes of daily brisk walking or jogging. This was done individually and supervised. Participants who missed > 2 training sessions were considered as non-completers. Exercise intensity had to be maintained within 65%-75% of age-predicted maximal heart rate, as commonly prescribed in studies using aerobic exercise to alleviate depression. Heart rate monitoring devices were used. Participants in the stretching (ST) group also performed a daily 30 minutes exercise program but this was sham exercise, consisting of stretching exercises. Several muscle groups (thighs, calves, gluteal, shoulders, back) were stretched for 60 seconds, with equivalent resting intervals between stretching series. These activities were also individual and supervised. As was the case for the AE intervention, participants who missed > 2 training sessions were considered as non-completers. Participants in the control (NI) group received no intervention other than prescribed medication. All participants started antidepressants within less than 2 weeks before study entry. Official Title ----------------- Efficacy of Exercise as an Adjunct Treatment for Clinically Depressed Inpatients During the Initial Stages of Antidepressant Therapy. Conditions ----------------- Major Depressive Disorder Intervention / Treatment ----------------- * Behavioral: physical exercise Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: diagnosis of major depressive disorder (MDD) antidepressant drug therapy initiated for less than 2 weeks score of 29 or more on the Beck depression inventory Exclusion Criteria: medical contraindication for exercise practice inability to understand written French beta-blocking drugs or another forms of antidepressant therapy (sleep deprivation, electroconvulsive therapy) Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: aerobic exercise (AE)<br>Intervention type: Behavioral. Intervention name: Aerobic exercise Intervention description: 10 days of daily aerobic exercise (brisk walking, jogging); duration: 30 minutes per session; intensity: 65%-75% of age-predicted maximal heart rate. All participants were treated with either paroxetine (20-50mg/day), fluoxetine (20-80mg/day) or bupropion (100-200mg/day). | Behavioral: physical exercise<br>* endurance-training or stretching (sham exercise)<br>| | Sham Comparator: stretching exercise (ST)<br>Intervention type: Behavioral. Intervention name: Stretching exercise Intervention description: 10 days of daily stretching exercise; duration: 30 minutes per session. All participants were treated with either paroxetine (20-50mg/day), fluoxetine (20-80mg/day) or bupropion (100-200mg/day). | Behavioral: physical exercise<br>* endurance-training or stretching (sham exercise)<br>| | No Intervention: no intervention (NI)<br>No behavioral intervention. All participants were treated with either paroxetine (20-50mg/day), fluoxetine (20-80mg/day) or bupropion (100-200mg/day). | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Score change on the 21-item Beck depression inventory (BDI-II). Each item has a set of severity-graded self-evaluative statements that are rated 0 (neutral) to 3 (maximum severity). | | Baseline and 10 days |

NCT01249092

Pentoxifylline for Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is cholestatic liver disease characterized by progressive destruction of small bile ducts within the liver that can lead to end stage liver disease and all its complications.~Although ursodeoxycholic acid (UDCA) is associated with increased survival in many patients with PBC, there is absence of an adequate response to UDCA in a significant proportion of PBC patients.~Tumor necrosis factor alpha (TNF-alpha) is a cytokine that plays an important role in the pathogenesis of PBC. Other fibrosis biomarkers such as tissue metallo proteinase 1 (TIMP-1) are associated with progression of liver fibrosis in PBC. Pentoxifylline (PTX) is a methylxanthine derivative that inhibits pro-inflammatory cytokines and also has shown anti-fibrotic effects in serum of patients with PBC. Furthermore, PTX has well known clinical and safety profiles. The main hypothesis of this study is that therapy with pentoxifylline (PTX) will result in improvement of liver disease in PBC patients who are incomplete responders to UDCA.~The focus of this proposal is on the effectiveness of PTX in improving laboratory parameters of liver disease and levels of cytokines involved in the pathogenesis of the disease in patients with PBC.

A Pilot Study of Pentoxifylline for the Treatment of Primary Biliary Cirrhosis

Primary Biliary Cirrhosis

* Drug: Pentoxifylline

Inclusion Criteria:~Male and female patients ages 18 to 76 years.~Established diagnosis of PBC based on at least three of the following criteria:~Detectable anti-mitochondrial antibodies (AMA)~Cholestatic biochemical pattern~Liver biopsy compatible with PBC~Appropriate exclusion of other liver diseases.~Therapy with UDCA at adequate dose (13-15mg/kg/d) for at least six months and evidence of suboptimal response defined by alkaline phosphatase levels that did not normalize and remain elevated by at least 1.5 times the upper limit of normal.~No history or present hepatic decompensation (e.g. variceal hemorrhage, encephalopathy, or poorly controlled ascites).~Exclusion Criteria:~Findings highly suggestive of liver disease of other etiology.~A score >=10 points on the Revised Scoring System for autoimmune hepatitis (AIH), supporting a diagnosis of PBC/AIH overlap.~Patients on steroids (systemic), immunosuppressants, or immunomodulatory agents within the previous 6 months.~Patients with clinical or laboratory evidence suggestive of decompensated cirrhosis.~Hypersensitivity to PTX or the methylxanthines (caffeine, theophylline, theobromine).~History of cerebral or retinal hemorrhage.~Other medical comorbidities (such as cardiac, renal, cancer) that would interfere with completion of the study.~Patients taking Theophylline or Coumadin because of potential drug-drug interactions with PTX. In addition, patients taking low molecular weight heparin preparations.~Pregnant or nursing women.

18 Years

76 Years

All

No

Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Serum Alkaline Phosphatase Levels. | Serum alkaline phosphatase levels at entry and at 6 months of therapy with PTX will be measured and compared. | 6 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Serum Concentration of Tissue Inhibitor Metalloproteinase 1 (TIMP-1) After PTX Therapy. | Serum concentration of tissue inhibitor metalloproteinase 1 (TIMP-1), a fibrosis biomarker of interest, will be measured and the change in serum levels between entry and end of study will be calculated. | 6 months | | Safety of Therapy in the Pilot Study of PTX Therapy in Patients With PBC Will be Assessed | The number of participants that experienced any severe adverse events will be monitored and recorded. | 6 months |

biliary cirrhosis

Pentoxifylline, Phosphodiesterase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Platelet Aggregation Inhibitors, Radiation-Protective Agents, Protective Agents, Physiological Effects of Drugs, Vasodilator Agents, Free Radical Scavengers, Antioxidants

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Pentoxifylline 400 mg TID<br>This study is an open label pilot with only one arm. | Drug: Pentoxifylline<br>* Patients will take 400mg of pentoxifylline three times daily for a total duration of 6 months.<br>|

Pentoxifylline for Primary Biliary Cirrhosis Study Overview ================= Brief Summary ----------------- Primary biliary cirrhosis (PBC) is cholestatic liver disease characterized by progressive destruction of small bile ducts within the liver that can lead to end stage liver disease and all its complications. Although ursodeoxycholic acid (UDCA) is associated with increased survival in many patients with PBC, there is absence of an adequate response to UDCA in a significant proportion of PBC patients. Tumor necrosis factor alpha (TNF-alpha) is a cytokine that plays an important role in the pathogenesis of PBC. Other fibrosis biomarkers such as tissue metallo proteinase 1 (TIMP-1) are associated with progression of liver fibrosis in PBC. Pentoxifylline (PTX) is a methylxanthine derivative that inhibits pro-inflammatory cytokines and also has shown anti-fibrotic effects in serum of patients with PBC. Furthermore, PTX has well known clinical and safety profiles. The main hypothesis of this study is that therapy with pentoxifylline (PTX) will result in improvement of liver disease in PBC patients who are incomplete responders to UDCA. The focus of this proposal is on the effectiveness of PTX in improving laboratory parameters of liver disease and levels of cytokines involved in the pathogenesis of the disease in patients with PBC. Official Title ----------------- A Pilot Study of Pentoxifylline for the Treatment of Primary Biliary Cirrhosis Conditions ----------------- Primary Biliary Cirrhosis Intervention / Treatment ----------------- * Drug: Pentoxifylline Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male and female patients ages 18 to 76 years. Established diagnosis of PBC based on at least three of the following criteria: Detectable anti-mitochondrial antibodies (AMA) Cholestatic biochemical pattern Liver biopsy compatible with PBC Appropriate exclusion of other liver diseases. Therapy with UDCA at adequate dose (13-15mg/kg/d) for at least six months and evidence of suboptimal response defined by alkaline phosphatase levels that did not normalize and remain elevated by at least 1.5 times the upper limit of normal. No history or present hepatic decompensation (e.g. variceal hemorrhage, encephalopathy, or poorly controlled ascites). Exclusion Criteria: Findings highly suggestive of liver disease of other etiology. A score >=10 points on the Revised Scoring System for autoimmune hepatitis (AIH), supporting a diagnosis of PBC/AIH overlap. Patients on steroids (systemic), immunosuppressants, or immunomodulatory agents within the previous 6 months. Patients with clinical or laboratory evidence suggestive of decompensated cirrhosis. Hypersensitivity to PTX or the methylxanthines (caffeine, theophylline, theobromine). History of cerebral or retinal hemorrhage. Other medical comorbidities (such as cardiac, renal, cancer) that would interfere with completion of the study. Patients taking Theophylline or Coumadin because of potential drug-drug interactions with PTX. In addition, patients taking low molecular weight heparin preparations. Pregnant or nursing women. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 76 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Pentoxifylline 400 mg TID<br>This study is an open label pilot with only one arm. | Drug: Pentoxifylline<br>* Patients will take 400mg of pentoxifylline three times daily for a total duration of 6 months.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Serum Alkaline Phosphatase Levels. | Serum alkaline phosphatase levels at entry and at 6 months of therapy with PTX will be measured and compared. | 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Serum Concentration of Tissue Inhibitor Metalloproteinase 1 (TIMP-1) After PTX Therapy. | Serum concentration of tissue inhibitor metalloproteinase 1 (TIMP-1), a fibrosis biomarker of interest, will be measured and the change in serum levels between entry and end of study will be calculated. | 6 months | | Safety of Therapy in the Pilot Study of PTX Therapy in Patients With PBC Will be Assessed | The number of participants that experienced any severe adverse events will be monitored and recorded. | 6 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- biliary cirrhosis

NCT04544930

Therapist-guided Internet Treatment for Hazardous and Harmful Alcohol Use. A Feasibility Study

The aim of the present study is to test the feasibility of therapist-guided Internet treatment for hazardous (risky) and harmful alcohol use among adults 18 years and older. The hypothesis is that the intervention is feasible and that it can help people change risky drinking habits at an early stage before developing into problems that are more serious.The therapist-guided Internet treatment addresses the person's need for confidentiality and contributes to reducing the stigma associated with visiting a substance abuse clinic.

Background:~A significant proportion of people with substance abuse do not seek help for their problems and therefore do not receive the necessary help at an early stage. An important reason for this is the stigma associated with substance abuse. Therapist-guided Internet treatment has been developed and tested in recent years as an approach that increases access to effective treatment for a variety of mental and substance-related problems and disorders. Internet-based interventions increase the patient's choice of type of treatment and give the patient an experience of having control over their own behavior change. Moreover, such treatment is independent of where you live, and you do not need to attend a clinic. In addition, by offering therapist-guided Internet treatment, therapists can treat far more patients compared to regular face-to-face treatment. In this way, the health services, which are already under severe pressure due to many new and competing tasks, are relieved.~Research questions:~Is therapist-guided Internet treatment for hazardous and harmful alcohol use feasible for self-referred persons?~What factors contribute/do not contribute to the feasibility of treatment?~Can the intervention help people change risky drinking habits before it develops into problems that are more serious?~How do participants experience the intervention?~Methods:~Participants:~A total of 30 participants will be recruited through announcements in social media, newspapers and through GP's and other health care services. Participants will be recruited from the catchment area of Haukeland University Hospital, Western Norway, and Vestfold Hospital, Eastern Norway.~Design:~The study will be conducted as an open, 6-months follow-up study, to assess whether the design is suitable for a randomized controlled trial in the next round. Both quantitative and qualitative methods will be used to investigate the feasibility of the treatment program.~Data collection:~Assessments will be carried out at start of treatment (T1), through the treatment course (T2) and at the end of treatment (T3) and at follow-up (T4). Qualitative interviews will be conducted at the end of treatment.~Intervention:~The treatment program is developed at Vestfold Hospital, Norway. It is based on Internet- based cognitive behavior therapy (ICBT). The treatment program consists of eight text-based self-help modules on the Internet that participants can access via secure login using Bank identification (ID) (security level 4). The self-help modules include psychoeducation, tasks and exercises. The therapist guidance is secondary to the self-help modules. The therapist provides feedback to the patient online in the secured program once a week.~Statistics:~Sample size:~Since this is a feasibility study primarily intended to test the feasibility of therapist-guided Internet treatment for hazardous and harmful alcohol use, the sample will be limited to 30 participants. Therefore, power analysis is not performed.~Statistical methods:~Both statistical and interpretative methods will be used. Descriptive statistics (percentages, means, standard deviations), as well as statistical and clinical change. Qualitative in-depth interviews will be analyzed using thematic content analysis.~Plan for activities and dissemination:~Scheduled start of data collection is September 2020. The data collection will continue until the summer of 2021. The follow-up period will be completed by the end of 2021.~The results of the feasibility study will be published in peer-reviewed journals. Furthermore, the results will be disseminated to the public through media (including social media), and as information aimed at both health and social care professionals, patient groups and user forums.

Therapist-guided Internet Treatment for Hazardous and Harmful Alcohol Use. a Feasibility Study

Alcohol Abuse, Internet-Based Intervention

* Behavioral: therapist-guided

Inclusion Criteria:~18 years or older~access to the Internet~interested in receiving Internet treatment for changing drinking habits~a score of 6 or higher for women and 8 or higher for men on the Alcohol Use Disorder Identification Test (AUDIT)~Exclusion Criteria:~diagnosed alcohol dependence or addiction to other drugs and already in treatment~serious reading and/or writing difficulties~cognitive impairment/dementia~severe mental disorder or in need of other treatment

18 Years

All

No

Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The Alcohol Use Disorders Identification Test (AUDIT) | AUDIT is a screening instrument consisting of 10 questions designed to identify hazardous (risky) and harmful use of alcohol in adults. Based on the 10 questions, a score is calculated indicating whether the person is at risk for developing more serious alcohol problems. A cut-off score of > 6 points indicates risky use in women, and a cut-off score of > 8 points indicates risky use in men. | AUDIT will measure whether there is a change in alcohol intake during the treatment period (8-12 weeks) and at follow-up (6 months after the end of treatment). | | The Timeline Followback (TLFB) for alcohol | TLFB for alcohol is an assessment tool that includes estimates of daily alcohol intake over a specific period, e.g. within seven days. TLFB provides information on various dimensions of the person's drinking habits, such as the number of drinking days and the maximum amount of alcohol consumed. | TLFB will calculate the intake of alcohol units (AE) and change in the seven-day period from the first assessment to the 6 months follow-up. |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The Drug-Taking Confidence Questionnaire (DTCQ). | DTCQ measures the person's confidence in his or her abilities to cope in situations that are high-risk for substance use. The tool yields information about client strengths and needs in the area of relapse potential in 50 different risk situations. | DTCQ will measure changes during the treatment course of 8-12 weeks, and at 6 months follow-up. | | Symptom Checklist -10 (SCL-10) | SCL-10 is a self-report questionnaire for identifying symptoms of psychological distress over the past seven days. SCL-10 contains 10 statements. | SCL-10 will measure changes in psychological distress during the treatment course of 8-12 weeks, and at 6 months follow-up. | | Patient Health Questionnaire, PHQ-9 | Patient Health Questionnaire (PHQ-9) consists of nine items and measures key symptoms of depression. | Patient Health Questionnaire (PHQ-9) will measure changes in symptoms of depression during the treatment course of 8-12 weeks, and at 6 months follow-up. | | General Anxiety Disorder (GAD-7). | GAD-7 is a screening instrument that consists of seven items and measures key symptoms of anxiety. | GAD-7 will measure changes in symptoms of anxiety during the treatment course of 8-12 weeks, and at 6 months follow-up. | | EuroQol five-dimensional (EQ-5D) descriptive system (EQ-5D-5L) | EQ-5D-5L measures health-related quality of life in five areas; mobility, personal care, activities of daily living, pain/discomfort and anxiety / depression | EQ-5D-5L will measure changes in health-related quality of life during the treatment course of 8-12 weeks, and at 6 months follow-up. |

Mental Disorders, Alcoholism, Alcohol-Related Disorders, Substance-Related Disorders, Chemically-Induced Disorders

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: therapist-guided<br>Therapist-guided Internet treatment based on cognitive behavior therapy (ICBT). | Behavioral: therapist-guided<br>* Therapist-guided Internet treatment comprises eight text modules on the Internet that include psychoeducation, tasks and exercises. Key elements are setting goals for treatment, identifying and challenging negative automatic thoughts through a number of exercises and behavioral experiments, as well as making a plan for relapse prevention. Therapist guidance is secondary to the self-help modules, and the therapist provides feedback to the patient online in the secured program once a week<br>|

Therapist-guided Internet Treatment for Hazardous and Harmful Alcohol Use. A Feasibility Study Study Overview ================= Brief Summary ----------------- The aim of the present study is to test the feasibility of therapist-guided Internet treatment for hazardous (risky) and harmful alcohol use among adults 18 years and older. The hypothesis is that the intervention is feasible and that it can help people change risky drinking habits at an early stage before developing into problems that are more serious.The therapist-guided Internet treatment addresses the person's need for confidentiality and contributes to reducing the stigma associated with visiting a substance abuse clinic. Detailed Description ----------------- Background: A significant proportion of people with substance abuse do not seek help for their problems and therefore do not receive the necessary help at an early stage. An important reason for this is the stigma associated with substance abuse. Therapist-guided Internet treatment has been developed and tested in recent years as an approach that increases access to effective treatment for a variety of mental and substance-related problems and disorders. Internet-based interventions increase the patient's choice of type of treatment and give the patient an experience of having control over their own behavior change. Moreover, such treatment is independent of where you live, and you do not need to attend a clinic. In addition, by offering therapist-guided Internet treatment, therapists can treat far more patients compared to regular face-to-face treatment. In this way, the health services, which are already under severe pressure due to many new and competing tasks, are relieved. Research questions: Is therapist-guided Internet treatment for hazardous and harmful alcohol use feasible for self-referred persons? What factors contribute/do not contribute to the feasibility of treatment? Can the intervention help people change risky drinking habits before it develops into problems that are more serious? How do participants experience the intervention? Methods: Participants: A total of 30 participants will be recruited through announcements in social media, newspapers and through GP's and other health care services. Participants will be recruited from the catchment area of Haukeland University Hospital, Western Norway, and Vestfold Hospital, Eastern Norway. Design: The study will be conducted as an open, 6-months follow-up study, to assess whether the design is suitable for a randomized controlled trial in the next round. Both quantitative and qualitative methods will be used to investigate the feasibility of the treatment program. Data collection: Assessments will be carried out at start of treatment (T1), through the treatment course (T2) and at the end of treatment (T3) and at follow-up (T4). Qualitative interviews will be conducted at the end of treatment. Intervention: The treatment program is developed at Vestfold Hospital, Norway. It is based on Internet- based cognitive behavior therapy (ICBT). The treatment program consists of eight text-based self-help modules on the Internet that participants can access via secure login using Bank identification (ID) (security level 4). The self-help modules include psychoeducation, tasks and exercises. The therapist guidance is secondary to the self-help modules. The therapist provides feedback to the patient online in the secured program once a week. Statistics: Sample size: Since this is a feasibility study primarily intended to test the feasibility of therapist-guided Internet treatment for hazardous and harmful alcohol use, the sample will be limited to 30 participants. Therefore, power analysis is not performed. Statistical methods: Both statistical and interpretative methods will be used. Descriptive statistics (percentages, means, standard deviations), as well as statistical and clinical change. Qualitative in-depth interviews will be analyzed using thematic content analysis. Plan for activities and dissemination: Scheduled start of data collection is September 2020. The data collection will continue until the summer of 2021. The follow-up period will be completed by the end of 2021. The results of the feasibility study will be published in peer-reviewed journals. Furthermore, the results will be disseminated to the public through media (including social media), and as information aimed at both health and social care professionals, patient groups and user forums. Official Title ----------------- Therapist-guided Internet Treatment for Hazardous and Harmful Alcohol Use. a Feasibility Study Conditions ----------------- Alcohol Abuse, Internet-Based Intervention Intervention / Treatment ----------------- * Behavioral: therapist-guided Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 18 years or older access to the Internet interested in receiving Internet treatment for changing drinking habits a score of 6 or higher for women and 8 or higher for men on the Alcohol Use Disorder Identification Test (AUDIT) Exclusion Criteria: diagnosed alcohol dependence or addiction to other drugs and already in treatment serious reading and/or writing difficulties cognitive impairment/dementia severe mental disorder or in need of other treatment Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: therapist-guided<br>Therapist-guided Internet treatment based on cognitive behavior therapy (ICBT). | Behavioral: therapist-guided<br>* Therapist-guided Internet treatment comprises eight text modules on the Internet that include psychoeducation, tasks and exercises. Key elements are setting goals for treatment, identifying and challenging negative automatic thoughts through a number of exercises and behavioral experiments, as well as making a plan for relapse prevention. Therapist guidance is secondary to the self-help modules, and the therapist provides feedback to the patient online in the secured program once a week<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The Alcohol Use Disorders Identification Test (AUDIT) | AUDIT is a screening instrument consisting of 10 questions designed to identify hazardous (risky) and harmful use of alcohol in adults. Based on the 10 questions, a score is calculated indicating whether the person is at risk for developing more serious alcohol problems. A cut-off score of > 6 points indicates risky use in women, and a cut-off score of > 8 points indicates risky use in men. | AUDIT will measure whether there is a change in alcohol intake during the treatment period (8-12 weeks) and at follow-up (6 months after the end of treatment). | | The Timeline Followback (TLFB) for alcohol | TLFB for alcohol is an assessment tool that includes estimates of daily alcohol intake over a specific period, e.g. within seven days. TLFB provides information on various dimensions of the person's drinking habits, such as the number of drinking days and the maximum amount of alcohol consumed. | TLFB will calculate the intake of alcohol units (AE) and change in the seven-day period from the first assessment to the 6 months follow-up. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The Drug-Taking Confidence Questionnaire (DTCQ). | DTCQ measures the person's confidence in his or her abilities to cope in situations that are high-risk for substance use. The tool yields information about client strengths and needs in the area of relapse potential in 50 different risk situations. | DTCQ will measure changes during the treatment course of 8-12 weeks, and at 6 months follow-up. | | Symptom Checklist -10 (SCL-10) | SCL-10 is a self-report questionnaire for identifying symptoms of psychological distress over the past seven days. SCL-10 contains 10 statements. | SCL-10 will measure changes in psychological distress during the treatment course of 8-12 weeks, and at 6 months follow-up. | | Patient Health Questionnaire, PHQ-9 | Patient Health Questionnaire (PHQ-9) consists of nine items and measures key symptoms of depression. | Patient Health Questionnaire (PHQ-9) will measure changes in symptoms of depression during the treatment course of 8-12 weeks, and at 6 months follow-up. | | General Anxiety Disorder (GAD-7). | GAD-7 is a screening instrument that consists of seven items and measures key symptoms of anxiety. | GAD-7 will measure changes in symptoms of anxiety during the treatment course of 8-12 weeks, and at 6 months follow-up. | | EuroQol five-dimensional (EQ-5D) descriptive system (EQ-5D-5L) | EQ-5D-5L measures health-related quality of life in five areas; mobility, personal care, activities of daily living, pain/discomfort and anxiety / depression | EQ-5D-5L will measure changes in health-related quality of life during the treatment course of 8-12 weeks, and at 6 months follow-up. |

NCT04948970

Steroid Panel for One-step Diagnosis of Adrenal Diseases

The aim of this study is to develop a one-step diagnostic method for adrenal diseases, Patients with adrenal diseases including non-functioning adrenal adenoma, adrenal Cushing's syndrome, primary aldosteronism, and pheochromocytoma will be recruited. Using mass spectrometry analysis based on a multisteroid panel, serum, urine, saliva, and hair samples of the patients will be analyzed. The diagnostic yield of each and combination of steroids will be evaluated.

Adrenal diseases consist of heterogenous diseases. To differentiate various adrenal diseases, multiple steps of diagnostic tests are needed. In this study, the investigators aimed to develop a one-step diagnostic method to differentiate various adrenal diseases using multisteroid panel.~About 400 patients with adrenal diseases including non-functioning adenoma, adrenal Cushing's syndrome, primary aldosteronism, and pheochromocytoma will be recruited. Serum, hair, saliva, and urine samples of the patients will be analyzed using mass spectrometry. Each and combination of multisteroid will be evaluated for diagnosing adrenal diseases.

Development of New Technology for One-step Diagnosis of Adrenal Diseases Based on Adrenal Hormone Panel

Adrenal Disease

Inclusion Criteria:~Patients who are diagnosed with adrenal diseases~Exclusion Criteria:~Taking medications that can affect steroid metabolism~Major depression, chronic alcoholism~Suspected cancer metastasis to adrenal glands~Other acute stress conditions

18 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Diagnostic accuracy of multisteroid panel for differentiating adrenal diseases | Evaluate how accurately the developed multisteroid panel diagnoses adrenal disease by measuring sensitivity (%) and specificity (%) for diagnosis of Cushing's syndrome.~Evaluate how accurately the developed multisteroid panel diagnoses adrenal disease by measuring sensitivity (%) and specificity (%) for diagnosis of primary aldosteronism.~Evaluate how accurately the developed multisteroid panel diagnoses adrenal disease by measuring sensitivity (%) and specificity (%) for diagnosis of pheochromocytoma. | Within 1 year after subject recruitment when the final diagnosis of adrenal diseases are made |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Diagnostic accuracy of each steroid component for differentiating adrenal diseases | Evaluate how accurately each component of the steroid panel differentiate adrenal diseases.~Sensitivity (%) and specificity (%) of each steroid measures for adrenal Cushing's syndrome will be calculated.~Sensitivity (%) and specificity (%) of each steroid measures for primary aldosteronism will be calculated.~Sensitivity (%) and specificity (%) of each steroid measures for pheochromocytoma will be calculated. | Within 1 year after subject recruitment when the final diagnosis of adrenal diseases are made |

Adrenal Gland Diseases, Endocrine System Diseases

Steroid Panel for One-step Diagnosis of Adrenal Diseases Study Overview ================= Brief Summary ----------------- The aim of this study is to develop a one-step diagnostic method for adrenal diseases, Patients with adrenal diseases including non-functioning adrenal adenoma, adrenal Cushing's syndrome, primary aldosteronism, and pheochromocytoma will be recruited. Using mass spectrometry analysis based on a multisteroid panel, serum, urine, saliva, and hair samples of the patients will be analyzed. The diagnostic yield of each and combination of steroids will be evaluated. Detailed Description ----------------- Adrenal diseases consist of heterogenous diseases. To differentiate various adrenal diseases, multiple steps of diagnostic tests are needed. In this study, the investigators aimed to develop a one-step diagnostic method to differentiate various adrenal diseases using multisteroid panel. About 400 patients with adrenal diseases including non-functioning adenoma, adrenal Cushing's syndrome, primary aldosteronism, and pheochromocytoma will be recruited. Serum, hair, saliva, and urine samples of the patients will be analyzed using mass spectrometry. Each and combination of multisteroid will be evaluated for diagnosing adrenal diseases. Official Title ----------------- Development of New Technology for One-step Diagnosis of Adrenal Diseases Based on Adrenal Hormone Panel Conditions ----------------- Adrenal Disease Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients who are diagnosed with adrenal diseases Exclusion Criteria: Taking medications that can affect steroid metabolism Major depression, chronic alcoholism Suspected cancer metastasis to adrenal glands Other acute stress conditions Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Diagnostic accuracy of multisteroid panel for differentiating adrenal diseases | Evaluate how accurately the developed multisteroid panel diagnoses adrenal disease by measuring sensitivity (%) and specificity (%) for diagnosis of Cushing's syndrome. Evaluate how accurately the developed multisteroid panel diagnoses adrenal disease by measuring sensitivity (%) and specificity (%) for diagnosis of primary aldosteronism. Evaluate how accurately the developed multisteroid panel diagnoses adrenal disease by measuring sensitivity (%) and specificity (%) for diagnosis of pheochromocytoma. | Within 1 year after subject recruitment when the final diagnosis of adrenal diseases are made | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Diagnostic accuracy of each steroid component for differentiating adrenal diseases | Evaluate how accurately each component of the steroid panel differentiate adrenal diseases. Sensitivity (%) and specificity (%) of each steroid measures for adrenal Cushing's syndrome will be calculated. Sensitivity (%) and specificity (%) of each steroid measures for primary aldosteronism will be calculated. Sensitivity (%) and specificity (%) of each steroid measures for pheochromocytoma will be calculated. | Within 1 year after subject recruitment when the final diagnosis of adrenal diseases are made |

NCT02057068

Improving Sleep in Veterans and Their CGs

This study addresses the neglected topic of sleep disturbance in older caregiving dyads-a topic that has important implications for the safety, health, functioning and quality of life of older Veterans living at home and being cared for by a family caregiver (CG). The purpose of the study was to develop and field test non-pharmacological, technology enhanced sleep hygiene, exercise and meditation interventions to improve sleep in Veteran caregiving dyads.The conceptual framework of the intervention incorporated components of cognitive behavioral therapy, psycho-education and self-management support for individuals with chronic conditions with an emphasis on cultivating competence and mastery.

Research Plan:~Sample. Veteran care receivers(CR s) or carepartners (CP) over the age of 60 who require assistance from a spousal or cohabitating caregiver (CG) and Veteran caregivers providing care for a cohabitating carepartner were recruited. Dyads underwent comprehensive baseline assessments consisting of in-person home-based interviews and iPad training (T1) followed by a week-long data collection of contemporaneous actigraphic sleep parameters and twice daily (morning and evening) indices of subjective sleep, activity, mood, behavior and sleep hygiene completed on the Tonic for Health Platform. Dyads were randomly assigned to an immediate intervention or wait-list control group. The immediate group received the intervention described below followed by post-intervention assessments (T2) identical to baseline. Wait-list participants then received the intervention followed by a final post-intervention assessment for the wait-list group only (T3).~Intervention.~Daily Videos: Video modules were delivered daily to the dyads' iPads during the 6-week intervention. All participants received core programming of sleep hygiene education, and guided instruction for daily physical activity enhancement Move-Out! and meditation/relaxation/self-care Stand Down! sessions individualized to functional ability levels. The baseline data allowed for subsequent compilation and programming of individualized, algorithmically derived, adaptive prescriptions for relevant video modules, sleep hygiene recommendations and cognitive behavioral strategies based upon the three independent streams of objective and subjective data for each dyad member. During the intervention dyads completed brief morning and evening diaries to assess compliance with the intervention and capture daily mood and sleep/sleep hygiene data.~Tele-Video-Conferences: Each dyad participated in two tele-video conferences with the PI. The first was to discuss evaluation results, obtain buy-in for the prescribed intervention and address dysfunctional beliefs and attitudes about sleep. The second call was a check-in, encouragement, reinforcement and coaching call. Dyads were re-assessed following the 6-week intervention.~Evaluations:~Standardized quantitative evaluations regarding the utility of the program were completed following the post-intervention assessments on the iPads. A sub-sample of dyads also participated in qualitative interviews.

Improving Sleep In Veterans and Their Family Caregivers

Sleep Quality

* Behavioral: SLEEP-E Dyads Intervention

Inclusion Criteria:~Care recipient must be age 60 and over and require assistance from the identified caregiver with more than one Activity of Daily Living or three or more Instrumental Activities of Daily Living,~have a life expectancy of greater than or equal to six (6) months,~have no plans for transitioning out of home in the next six months,~and have approval from the primary care provider to participate in the research.~Caregivers must live with care recipient~Caregivers must obtain a negative mini-cog assessment or negative TICS-m assessment. Caregivers can be any relation (spouse, child, sibling, friend, etc.) to the care recipient so long as the two are cohabitating.~Caregiver can be any age.~For Phase 2 and Phase 3 of the study, either the care recipient or the caregiver must have difficulty sleeping as indicated by scores on the Insomnia Severity Index.~Exclusion Criteria:~Parkinson's with tremor or other movement disorder that would invalidate actigraphy~Untreated diagnosis of sleep apnea or restless leg syndrome~Inability to tolerate actigraphy~CG and CR sleep efficiency > 85% and/or both members of dyad report sleeping well~Caregivers must have a negative screen with the Mini-Cog or the ModifiedTelephone Interview for Cognitive Status (TICS-M) to demonstrate cognitive capacity to provide informed consent

18 Years

All

Accepts Healthy Volunteers

Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Sequential Assignment Interventional Model Description: Randomization to an immediate intervention group or a no-contact wait list control group. Following post intervention assessments the wait-list control group received the intervention. Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Subjective Sleep Quality | Pittsburgh Sleep Quality Index Scores (PSQI) The Pittsburgh Sleep Quality Index is a standardized and validated measure of subjective sleep quality and sleep disturbance. The inventory has 18-items. PSQI scores range from 0 - 21. A total score > 5 (some evidence for 8) is indicative of poor sleep quality. | Baseline (T1) and Post-Intervention (T2) - 8 Weeks |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Mean Sleep Efficiency | Average sleep efficiency over 7 nights of actigraphic measurement . Sleep efficiency is calculated as the number of hours asleep divided by the number of hours in bed with the intention to sleep. | Baseline (T1) and Post-Intervention (T2) - 8 Weeks | | BEF-SHI Total Number of Negative Sleep Hygiene Behaviors | Total Number of negative sleep hygiene indicators from the BEFSHI - Bedtime Environmental Features and Sleep Hygiene Index (e.g., nighttime caffeine, nighttime snacking-sugar, nicotine, excessive alcohol, excessive daytime napping, television, tablet and computer use in bedroom after 9 pm etc.) Participants are asked to respond yes (1) or no (0) to a series of sleep hygiene behaviors considered detrimental to sleep. Scores are summed. Possible scores range from 0-8 with a greater score indicating a greater number of negative sleep hygiene behaviors endorsed. | Baseline (T1) and Post-Intervention (T2) - 8 Weeks |

Caregivers, Telemedicine, Sleep Disorders, Meditation, Cognitive Behavioral Therapy, Activity Enhancement, Technology, Non-pharmacological sleep intervention

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: SLEEP-E Dyads Intervention<br>SLEEP-E Dyads Six-Week Tele-Health Intervention~. Daily core video modules on sleep education, sleep hygiene and behavioral and environmental factors influencing sleep.~. Daily and on-demand video modules designed to promote and provide guided instruction for daily Move Out time consisting of activity enhancement and exercise.~. Daily and on-demand video modules designed to promote and provide guided instruction for daily Stand Down time (meditation, therapeutic breathing and self-care).~. SLEEP-E Dyads book~. Two tele-video conferences to discuss evaluation results, obtain buy-in for the prescribed intervention and address dysfunctional beliefs and attitudes about sleep. The second call involves checking-in, encouragement, reinforcement and coaching | Behavioral: SLEEP-E Dyads Intervention<br>* Described in arm/group description<br>| | No Intervention: Usual Care Group<br>During the intervention period there is no data collection or contact with research staff other than for scheduling outcomes visits. | |

Improving Sleep in Veterans and Their CGs Study Overview ================= Brief Summary ----------------- This study addresses the neglected topic of sleep disturbance in older caregiving dyads-a topic that has important implications for the safety, health, functioning and quality of life of older Veterans living at home and being cared for by a family caregiver (CG). The purpose of the study was to develop and field test non-pharmacological, technology enhanced sleep hygiene, exercise and meditation interventions to improve sleep in Veteran caregiving dyads.The conceptual framework of the intervention incorporated components of cognitive behavioral therapy, psycho-education and self-management support for individuals with chronic conditions with an emphasis on cultivating competence and mastery. Detailed Description ----------------- Research Plan: Sample. Veteran care receivers(CR s) or carepartners (CP) over the age of 60 who require assistance from a spousal or cohabitating caregiver (CG) and Veteran caregivers providing care for a cohabitating carepartner were recruited. Dyads underwent comprehensive baseline assessments consisting of in-person home-based interviews and iPad training (T1) followed by a week-long data collection of contemporaneous actigraphic sleep parameters and twice daily (morning and evening) indices of subjective sleep, activity, mood, behavior and sleep hygiene completed on the Tonic for Health Platform. Dyads were randomly assigned to an immediate intervention or wait-list control group. The immediate group received the intervention described below followed by post-intervention assessments (T2) identical to baseline. Wait-list participants then received the intervention followed by a final post-intervention assessment for the wait-list group only (T3). Intervention. Daily Videos: Video modules were delivered daily to the dyads' iPads during the 6-week intervention. All participants received core programming of sleep hygiene education, and guided instruction for daily physical activity enhancement Move-Out! and meditation/relaxation/self-care Stand Down! sessions individualized to functional ability levels. The baseline data allowed for subsequent compilation and programming of individualized, algorithmically derived, adaptive prescriptions for relevant video modules, sleep hygiene recommendations and cognitive behavioral strategies based upon the three independent streams of objective and subjective data for each dyad member. During the intervention dyads completed brief morning and evening diaries to assess compliance with the intervention and capture daily mood and sleep/sleep hygiene data. Tele-Video-Conferences: Each dyad participated in two tele-video conferences with the PI. The first was to discuss evaluation results, obtain buy-in for the prescribed intervention and address dysfunctional beliefs and attitudes about sleep. The second call was a check-in, encouragement, reinforcement and coaching call. Dyads were re-assessed following the 6-week intervention. Evaluations: Standardized quantitative evaluations regarding the utility of the program were completed following the post-intervention assessments on the iPads. A sub-sample of dyads also participated in qualitative interviews. Official Title ----------------- Improving Sleep In Veterans and Their Family Caregivers Conditions ----------------- Sleep Quality Intervention / Treatment ----------------- * Behavioral: SLEEP-E Dyads Intervention Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Care recipient must be age 60 and over and require assistance from the identified caregiver with more than one Activity of Daily Living or three or more Instrumental Activities of Daily Living, have a life expectancy of greater than or equal to six (6) months, have no plans for transitioning out of home in the next six months, and have approval from the primary care provider to participate in the research. Caregivers must live with care recipient Caregivers must obtain a negative mini-cog assessment or negative TICS-m assessment. Caregivers can be any relation (spouse, child, sibling, friend, etc.) to the care recipient so long as the two are cohabitating. Caregiver can be any age. For Phase 2 and Phase 3 of the study, either the care recipient or the caregiver must have difficulty sleeping as indicated by scores on the Insomnia Severity Index. Exclusion Criteria: Parkinson's with tremor or other movement disorder that would invalidate actigraphy Untreated diagnosis of sleep apnea or restless leg syndrome Inability to tolerate actigraphy CG and CR sleep efficiency > 85% and/or both members of dyad report sleeping well Caregivers must have a negative screen with the Mini-Cog or the ModifiedTelephone Interview for Cognitive Status (TICS-M) to demonstrate cognitive capacity to provide informed consent Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Sequential Assignment Interventional Model Description: Randomization to an immediate intervention group or a no-contact wait list control group. Following post intervention assessments the wait-list control group received the intervention. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: SLEEP-E Dyads Intervention<br>SLEEP-E Dyads Six-Week Tele-Health Intervention . Daily core video modules on sleep education, sleep hygiene and behavioral and environmental factors influencing sleep. . Daily and on-demand video modules designed to promote and provide guided instruction for daily Move Out time consisting of activity enhancement and exercise. . Daily and on-demand video modules designed to promote and provide guided instruction for daily Stand Down time (meditation, therapeutic breathing and self-care). . SLEEP-E Dyads book . Two tele-video conferences to discuss evaluation results, obtain buy-in for the prescribed intervention and address dysfunctional beliefs and attitudes about sleep. The second call involves checking-in, encouragement, reinforcement and coaching | Behavioral: SLEEP-E Dyads Intervention<br>* Described in arm/group description<br>| | No Intervention: Usual Care Group<br>During the intervention period there is no data collection or contact with research staff other than for scheduling outcomes visits. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Subjective Sleep Quality | Pittsburgh Sleep Quality Index Scores (PSQI) The Pittsburgh Sleep Quality Index is a standardized and validated measure of subjective sleep quality and sleep disturbance. The inventory has 18-items. PSQI scores range from 0 - 21. A total score > 5 (some evidence for 8) is indicative of poor sleep quality. | Baseline (T1) and Post-Intervention (T2) - 8 Weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Mean Sleep Efficiency | Average sleep efficiency over 7 nights of actigraphic measurement . Sleep efficiency is calculated as the number of hours asleep divided by the number of hours in bed with the intention to sleep. | Baseline (T1) and Post-Intervention (T2) - 8 Weeks | | BEF-SHI Total Number of Negative Sleep Hygiene Behaviors | Total Number of negative sleep hygiene indicators from the BEFSHI - Bedtime Environmental Features and Sleep Hygiene Index (e.g., nighttime caffeine, nighttime snacking-sugar, nicotine, excessive alcohol, excessive daytime napping, television, tablet and computer use in bedroom after 9 pm etc.) Participants are asked to respond yes (1) or no (0) to a series of sleep hygiene behaviors considered detrimental to sleep. Scores are summed. Possible scores range from 0-8 with a greater score indicating a greater number of negative sleep hygiene behaviors endorsed. | Baseline (T1) and Post-Intervention (T2) - 8 Weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Caregivers, Telemedicine, Sleep Disorders, Meditation, Cognitive Behavioral Therapy, Activity Enhancement, Technology, Non-pharmacological sleep intervention

NCT03654339

Microsurgical vs Macro Surgical Approach for Grade II Gingival Recessions Employing Laterally Repositioned Flap

This study was conducted to assess the evaluation of micro and Macro surgical approach in the treatment of grade II gingival recessions using the laterally repositioned flap

In this study total, 30 patients were selected The patients initially received a comprehensive periodontal examination and complete plaque control program including oral hygiene to eliminate habits related to the aetiology of recession. Scaling, root planning and occlusal adjustments were done The patients were randomly assigned and divided into two groups. Group A and Group B. Patients with miller class II were treated with a laterally repositioned flap to obtain root coverage using conventional macrosurgical approach (15patients) and microsurgical approach(15patients)~The clinical parameters evaluated were height of gingival recession relative clinical attachment level which was measured as the distance from a fixed point in a stent to the bottom of the pocket and gingival biotype at baseline, 3 months and 6 months period

Comparison of Conventional vs Microsurgical Method for Root Coverage by Lateral Displacement Flap

Gingival Recession, Localized

* Procedure: root coverage

Inclusion Criteria:~Age 20-50 yrs~ClassII gingival recession~Vital teeth that were free from caries or inadequate restorations~Sufficient width of attached gingiva~Exclusion Criteria:~Any systemic diseases and smokers~ClassI,III&IV gingival recession~Abnormal frenal attachments~Interdental bone loss with tooth mobility

20 Years

50 Years

All

Accepts Healthy Volunteers

Primary Purpose: Treatment Intervention Model: Single Group Assignment Interventional Model Description: The patients will be equally divided into two test groups. Group A and Group B after phase I therapy. the group A patients will be treated with laterally repositioned flap to obtain root coverage using microsurgical approach. The group B patients will be treated with laterally repositioned flap to obtain root coverage using macrosurgical approach Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | vertical depth of recession | The height of gingival recession: From cementoenamel junction to the free gingival margin. | Change in level of gingival margin from baseline to 6 months. |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | horizontal width of recession | The width of gingival recession: Horizontal dimension of gingival defect at the level of Cementoenamel junction.. | Change in horizontal dimension of gingival margin from baseline to 6 months. |

Gingival Recession, Gingival Diseases, Periodontal Diseases, Mouth Diseases, Stomatognathic Diseases, Periodontal Atrophy

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: experimental group<br>Group A-15 patients were allocated to the microsurgical group for root coverage. following scaling and root planning, the laterally repositioned flap was done using the microsurgical approach~Group B-15 Patients were allocated to the conventional group for root coverage following scaling and root planning, the laterally repositioned flap was done using the macrosurgical approach | Procedure: root coverage<br>* Group A: After administration of local anaesthesia using ophthalmic microsurgical knives a V-shaped incision was made in the gingival recession area. the gingiva was removed .the adjacent partial thickness pedicle flap was reflected from the donor area .the pedicle flap was then covered over the recipient site. then secured with 6-0 absorbable sling suture without tension. the surgical procedure was done with seilar microscope 40X magnification.~Group B: After administration of local anaesthesia using 15 no blade a V-shaped incision was made in the gingival recession area . gingiva was removed .the adjacent partial thickness pedicle flap was reflected from the donor area .the pedicle flap was then covered over the recipient site. then carefully secured with 4-0 absorbable sling suture<br>|

Microsurgical vs Macro Surgical Approach for Grade II Gingival Recessions Employing Laterally Repositioned Flap Study Overview ================= Brief Summary ----------------- This study was conducted to assess the evaluation of micro and Macro surgical approach in the treatment of grade II gingival recessions using the laterally repositioned flap Detailed Description ----------------- In this study total, 30 patients were selected The patients initially received a comprehensive periodontal examination and complete plaque control program including oral hygiene to eliminate habits related to the aetiology of recession. Scaling, root planning and occlusal adjustments were done The patients were randomly assigned and divided into two groups. Group A and Group B. Patients with miller class II were treated with a laterally repositioned flap to obtain root coverage using conventional macrosurgical approach (15patients) and microsurgical approach(15patients) The clinical parameters evaluated were height of gingival recession relative clinical attachment level which was measured as the distance from a fixed point in a stent to the bottom of the pocket and gingival biotype at baseline, 3 months and 6 months period Official Title ----------------- Comparison of Conventional vs Microsurgical Method for Root Coverage by Lateral Displacement Flap Conditions ----------------- Gingival Recession, Localized Intervention / Treatment ----------------- * Procedure: root coverage Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 20-50 yrs ClassII gingival recession Vital teeth that were free from caries or inadequate restorations Sufficient width of attached gingiva Exclusion Criteria: Any systemic diseases and smokers ClassI,III&IV gingival recession Abnormal frenal attachments Interdental bone loss with tooth mobility Ages Eligible for Study ----------------- Minimum Age: 20 Years Maximum Age: 50 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Interventional Model Description: The patients will be equally divided into two test groups. Group A and Group B after phase I therapy. the group A patients will be treated with laterally repositioned flap to obtain root coverage using microsurgical approach. The group B patients will be treated with laterally repositioned flap to obtain root coverage using macrosurgical approach Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: experimental group<br>Group A-15 patients were allocated to the microsurgical group for root coverage. following scaling and root planning, the laterally repositioned flap was done using the microsurgical approach Group B-15 Patients were allocated to the conventional group for root coverage following scaling and root planning, the laterally repositioned flap was done using the macrosurgical approach | Procedure: root coverage<br>* Group A: After administration of local anaesthesia using ophthalmic microsurgical knives a V-shaped incision was made in the gingival recession area. the gingiva was removed .the adjacent partial thickness pedicle flap was reflected from the donor area .the pedicle flap was then covered over the recipient site. then secured with 6-0 absorbable sling suture without tension. the surgical procedure was done with seilar microscope 40X magnification. Group B: After administration of local anaesthesia using 15 no blade a V-shaped incision was made in the gingival recession area . gingiva was removed .the adjacent partial thickness pedicle flap was reflected from the donor area .the pedicle flap was then covered over the recipient site. then carefully secured with 4-0 absorbable sling suture<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | vertical depth of recession | The height of gingival recession: From cementoenamel junction to the free gingival margin. | Change in level of gingival margin from baseline to 6 months. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | horizontal width of recession | The width of gingival recession: Horizontal dimension of gingival defect at the level of Cementoenamel junction.. | Change in horizontal dimension of gingival margin from baseline to 6 months. |

NCT05465863

Humoral and Cellular İmmune Response to SARS-CoV-2 mRNA BNT162b2 Vaccine in Children With Chronic Kidney Diseases

Coronavirus 2019 (COVID-19) infection is associated with higher morbidity and mortality in adult patients on dialysis, and kidney transplant recipients (KTRs). Although children had lower morbidity and mortality, KTRs are more vulnerable than healthy children.~It has already known that the general immune responses to vaccines, which are currently in practice (attenuated, conjugated, or recombinant) were lower than healthy controls in children and adolescents on dialysis and with a kidney transplantation. Uremic milieu and immunosuppressive drugs are the factors causing impaired immune response in this group of patients. The new mRNA vaccine technology is used worldwide including children and adolescents during the pandemic. Studies have demonstrated lower immune response to new SARS-CoV-2 mRNA vaccine in adult KTRs. However, there is limited data about vaccine-induced immune response in children and adolescent with renal replacement therapy.~The aim of this study was to assess immune response to SARS-CoV-2 mRNA BNT162b2 and its clinical and laboratory correlates in children and adolescent KTRs. Humoral immune response was assessed by anti-SARS-CoV-2 immunoglobulin G (Anti-S IgG) and its clinical correlate neutralizing antibody (nAb). Cellular immune response was assessed with SARS-CoV-2 specific Interferon ɣ release assay (IGRA).

This is a prospective, multicenter case-control study performed between September 2021 and March 2022 in the Pediatric Nephrology Units of IU- Cerrahpaşa School of Medicine, Memorial Hospital, Marmara University School of Medicine, IU- Istanbul School of Medicine, Medeniyet University School of Medicine, and Istinye University School of Medicine. The control group has consisted of age and gender comparable 19 healthy children without any acute infection or chronic disease, who were admitted to Cerrahpasa School of Medicine, Pediatric out-patient unit for routine control.~When permitted by local guidelines, children and adolescents who were over 12 years old were notified of vaccine eligibility and encouraged to schedule an appointment. The SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer-BioNTech®) administered to all participants by intramuscular route in the deltoid region. At least one month after the second dose of the vaccine, serum samples and whole blood samples were collected from all patients and controls, to analyze the humoral and cellular immune response to the vaccine. All samples were stored at -20 ◦C until testing. SARS-CoV-2 PCR test results were recorded retrospectively to determine natural infection.

Humoral and Cellular İmmune Response to SARS-CoV-2 mRNA BNT162b2 Vaccine in Pediatric Kidney Transplant Recipients Compared to Dialysis Patients and Healthy Children

Chronic Kidney Disease 5D, Chronic Kidney Disease 5T

* Biological: SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer-BioNTech®)

Inclusion Criteria:~12-21 year-old chronic kidney diseases and dialysis patients~Exclusion Criteria:~Patients with primary immune deficiencies and not vaccinated with SARS-CoV-2 mRNA BNT162b2 vaccine~Patients who did not completed 2 series of SARS-CoV-2 mRNA BNT162b2 vaccine

12 Years

19 Years

All

Accepts Healthy Volunteers

Primary Purpose: Prevention Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Evaluation of the antibody response following vaccination | Anti-SARS-CoV-2 IgG Quantification and Neutralisation test | one month after the second dose of the vaccine |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Evaluation of the cellular response following vaccination | Interferon Gamma Release Assay | one month after the second dose of the vaccine |

children, chronic kidney disease, covid19, vaccination, antibody response

Kidney Diseases, Renal Insufficiency, Chronic, Urologic Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases, Renal Insufficiency, Chronic Disease, Disease Attributes, Pathologic Processes

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Patients<br> | Biological: SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer-BioNTech®)<br>* When permitted by local guidelines, children and adolescents who were over 12 years old were notified of vaccine eligibility and encouraged to schedule an appointment<br>| | Active Comparator: Healthy controls<br> | Biological: SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer-BioNTech®)<br>* When permitted by local guidelines, children and adolescents who were over 12 years old were notified of vaccine eligibility and encouraged to schedule an appointment<br>|

Humoral and Cellular İmmune Response to SARS-CoV-2 mRNA BNT162b2 Vaccine in Children With Chronic Kidney Diseases Study Overview ================= Brief Summary ----------------- Coronavirus 2019 (COVID-19) infection is associated with higher morbidity and mortality in adult patients on dialysis, and kidney transplant recipients (KTRs). Although children had lower morbidity and mortality, KTRs are more vulnerable than healthy children. It has already known that the general immune responses to vaccines, which are currently in practice (attenuated, conjugated, or recombinant) were lower than healthy controls in children and adolescents on dialysis and with a kidney transplantation. Uremic milieu and immunosuppressive drugs are the factors causing impaired immune response in this group of patients. The new mRNA vaccine technology is used worldwide including children and adolescents during the pandemic. Studies have demonstrated lower immune response to new SARS-CoV-2 mRNA vaccine in adult KTRs. However, there is limited data about vaccine-induced immune response in children and adolescent with renal replacement therapy. The aim of this study was to assess immune response to SARS-CoV-2 mRNA BNT162b2 and its clinical and laboratory correlates in children and adolescent KTRs. Humoral immune response was assessed by anti-SARS-CoV-2 immunoglobulin G (Anti-S IgG) and its clinical correlate neutralizing antibody (nAb). Cellular immune response was assessed with SARS-CoV-2 specific Interferon ɣ release assay (IGRA). Detailed Description ----------------- This is a prospective, multicenter case-control study performed between September 2021 and March 2022 in the Pediatric Nephrology Units of IU- Cerrahpaşa School of Medicine, Memorial Hospital, Marmara University School of Medicine, IU- Istanbul School of Medicine, Medeniyet University School of Medicine, and Istinye University School of Medicine. The control group has consisted of age and gender comparable 19 healthy children without any acute infection or chronic disease, who were admitted to Cerrahpasa School of Medicine, Pediatric out-patient unit for routine control. When permitted by local guidelines, children and adolescents who were over 12 years old were notified of vaccine eligibility and encouraged to schedule an appointment. The SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer-BioNTech®) administered to all participants by intramuscular route in the deltoid region. At least one month after the second dose of the vaccine, serum samples and whole blood samples were collected from all patients and controls, to analyze the humoral and cellular immune response to the vaccine. All samples were stored at -20 ◦C until testing. SARS-CoV-2 PCR test results were recorded retrospectively to determine natural infection. Official Title ----------------- Humoral and Cellular İmmune Response to SARS-CoV-2 mRNA BNT162b2 Vaccine in Pediatric Kidney Transplant Recipients Compared to Dialysis Patients and Healthy Children Conditions ----------------- Chronic Kidney Disease 5D, Chronic Kidney Disease 5T Intervention / Treatment ----------------- * Biological: SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer-BioNTech®) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 12-21 year-old chronic kidney diseases and dialysis patients Exclusion Criteria: Patients with primary immune deficiencies and not vaccinated with SARS-CoV-2 mRNA BNT162b2 vaccine Patients who did not completed 2 series of SARS-CoV-2 mRNA BNT162b2 vaccine Ages Eligible for Study ----------------- Minimum Age: 12 Years Maximum Age: 19 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Patients<br> | Biological: SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer-BioNTech®)<br>* When permitted by local guidelines, children and adolescents who were over 12 years old were notified of vaccine eligibility and encouraged to schedule an appointment<br>| | Active Comparator: Healthy controls<br> | Biological: SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer-BioNTech®)<br>* When permitted by local guidelines, children and adolescents who were over 12 years old were notified of vaccine eligibility and encouraged to schedule an appointment<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Evaluation of the antibody response following vaccination | Anti-SARS-CoV-2 IgG Quantification and Neutralisation test | one month after the second dose of the vaccine | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Evaluation of the cellular response following vaccination | Interferon Gamma Release Assay | one month after the second dose of the vaccine | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- children, chronic kidney disease, covid19, vaccination, antibody response

NCT05697263

The Impact of the Menstrual Cycle on Physical Exercise and Performance

The menstrual cycle implies a basic difference in the biology of women and men but the effect of the hormonal variation on training protocols and physical performance is still not fully understood. Despite no existing evidence, the advice to periodize exercise according to the menstrual cycle has been widely spread among elite athletes, coaches, and sports federations. The advice is based on underpowered studies with considerable methodological weaknesses regarding determination of cycle phase, inclusion of athletes and lack of adequate control groups.~The purpose of this randomized, controlled study is to evaluate the effect of exercise periodization on aerobic fitness during different phases of the menstrual cycle. Further, the effect will be related to premenstrual symptoms, body composition and skeletal muscle morphology, sex hormone receptors, metabolic enzymes, and markers of muscle protein synthesis. This study will be well controlled and follow methodology recommendations for menstrual cycle research in sports and exercise.~Female athletes of fertile age will be randomized to different training regimens during three menstrual cycles (12 weeks):~Group A: Training three times a week throughout the menstrual cycle. Group B: Follicular phase-based training five times a week during the follicular phase and thereafter once a week during the luteal phase.~Group C: Luteal phase-based training five times a week during the luteal phase and once a week in the follicular phase.~The exercise will consist of high intensity intermittent spinning classes. Assessment of aerobic fitness and power will be performed at baseline, and again after three completed menstrual cycles. On the same day, body composition will be examined by DXA and blood samples will be collected for analysis of hormones and binding proteins. To confirm menstrual cycle phase, blood samples will be collected for hormone determination, and urinary stick will be used for detection of ovulation. Subjective ratings of menstrual cycle related symptoms will be performed every day. In a subgroup of women, muscle biopsies will be collected from m vastus lateralis at baseline and at the end of the study. This study will contribute to improved knowledge about exercise periodization in relation to the menstrual cycle. Well-grounded data is crucial to give evidence-based recommendations to female athletes when planning their training protocol to optimize training results and performance.

The Impact of the Menstrual Cycle on Physical Exercise and Performance

Women's Health, Menstrual Cycle, Exercise, Athletic Performance

* Other: Periodization of training

Inclusion Criteria:~Women exercising at least 3-4 times a week on a high level~Regular menstrual cycle with 26-32 cycle days.~Fully healthy and be able to follow the training program.~Exclusion Criteria:~Hormonal contraceptive users,~Users of regular medication~Chronic disease~Past or present neurological disorder~Recent musculoskeletal injury

18 Years

35 Years

Female

Accepts Healthy Volunteers

Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in aerobic performance | Cosmeds K5 Wearable Metabolic System will be used for breath-by-breath gas exchange measurements. Change in VO2peak from baseline to end of study will be evaluated. | Change from baseline aerobic performance at the end of Cycle 4 (each cycle is around 28 days) |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in muscle strength | A standardized isokinetic device (Biodex®, Corp, Shirley, NY, USA) will be used for measurements of maximal muscle torque (Nm) in the leg extensor muscles at 90 and 120 gr/sec (11). Change in muscle strength from baseline to end of study will be compared between groups. | Change from baseline muscle strength at the end of Cycle 4 (each cycle is around 28 days) | | Change in one-leg sit-to-stand test | Assessment of functional muscle strength in the lower extremities. | Change from baseline test at the end of Cycle 4 (each cycle is around 28 days) | | Change in one-leg hop test for distance | Assessment of functional muscle strength in the lower extremities. | Change from baseline test at the end of Cycle 4 (each cycle is around 28 days) | | Change in body composition | Differences in body fat (%) will be determined by DXA (Lunar equipment). | Change from baseline body composition at the end of Cycle 4 (each cycle is around 28 days) | | Change in body composition | Differences in muscle mass (g), will be determined by DXA (Lunar equipment). | Change from baseline body composition at the end of Cycle 4 (each cycle is around 28 days) | | Premenstrual symptoms | Prospective ratings of premenstrual symptoms will be performed with the Cyclicity Diagnoser | Every day during the study period | | Change in metabolic serum markers | Blood samples for analysis of IGF-1. | Change from baseline metabolic serum markers at the end of Cycle 4 (each cycle is around 28 days) | | Change in mucle morphology | Muscle biopsy in mm vastus lateralis | Change from baseline muscle morphology at the end of Cycle 4 (each cycle is around 28 days) | | Change in muscle tissue steroid hormones | Muscle biopsy in mm vastus lateralis | Change from baseline muscle tissue steroid hormones at the end of Cycle 4 (each cycle is around 28 days) | | Change in muscle protein synthesis | Muscle biopsy in mm vastus lateralis | Change from baseline muscle protein synthesis at the end of Cycle 4 (each cycle is around 28 days) | | Dysmenorrhea | Questionnaire | Through study completion, an average of 4 month |

Menstrual Cycle, Exercise, Women's Health, Athletic Performance

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Follicle phase based training<br>Follicular phase-based training five times a week during the follicular phase (the first two weeks of the menstrual cycle) and thereafter once a week for the rest of the cycle. | Other: Periodization of training<br>* Participants in the three arms will exercise the same dose and number of sessions distributed in three different ways.<br>| | Experimental: Luteal phase based training<br>Luteal phase-based training five times a week during the luteal phase (from ovulation to next menstruation) and once a week in the follicular phase. | Other: Periodization of training<br>* Participants in the three arms will exercise the same dose and number of sessions distributed in three different ways.<br>| | Experimental: Regular training<br>Regular training three times a week throughout the menstrual cycle (control group). | Other: Periodization of training<br>* Participants in the three arms will exercise the same dose and number of sessions distributed in three different ways.<br>|

The Impact of the Menstrual Cycle on Physical Exercise and Performance Study Overview ================= Brief Summary ----------------- The menstrual cycle implies a basic difference in the biology of women and men but the effect of the hormonal variation on training protocols and physical performance is still not fully understood. Despite no existing evidence, the advice to periodize exercise according to the menstrual cycle has been widely spread among elite athletes, coaches, and sports federations. The advice is based on underpowered studies with considerable methodological weaknesses regarding determination of cycle phase, inclusion of athletes and lack of adequate control groups. The purpose of this randomized, controlled study is to evaluate the effect of exercise periodization on aerobic fitness during different phases of the menstrual cycle. Further, the effect will be related to premenstrual symptoms, body composition and skeletal muscle morphology, sex hormone receptors, metabolic enzymes, and markers of muscle protein synthesis. This study will be well controlled and follow methodology recommendations for menstrual cycle research in sports and exercise. Female athletes of fertile age will be randomized to different training regimens during three menstrual cycles (12 weeks): Group A: Training three times a week throughout the menstrual cycle. Group B: Follicular phase-based training five times a week during the follicular phase and thereafter once a week during the luteal phase. Group C: Luteal phase-based training five times a week during the luteal phase and once a week in the follicular phase. The exercise will consist of high intensity intermittent spinning classes. Assessment of aerobic fitness and power will be performed at baseline, and again after three completed menstrual cycles. On the same day, body composition will be examined by DXA and blood samples will be collected for analysis of hormones and binding proteins. To confirm menstrual cycle phase, blood samples will be collected for hormone determination, and urinary stick will be used for detection of ovulation. Subjective ratings of menstrual cycle related symptoms will be performed every day. In a subgroup of women, muscle biopsies will be collected from m vastus lateralis at baseline and at the end of the study. This study will contribute to improved knowledge about exercise periodization in relation to the menstrual cycle. Well-grounded data is crucial to give evidence-based recommendations to female athletes when planning their training protocol to optimize training results and performance. Official Title ----------------- The Impact of the Menstrual Cycle on Physical Exercise and Performance Conditions ----------------- Women's Health, Menstrual Cycle, Exercise, Athletic Performance Intervention / Treatment ----------------- * Other: Periodization of training Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Women exercising at least 3-4 times a week on a high level Regular menstrual cycle with 26-32 cycle days. Fully healthy and be able to follow the training program. Exclusion Criteria: Hormonal contraceptive users, Users of regular medication Chronic disease Past or present neurological disorder Recent musculoskeletal injury Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 35 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Follicle phase based training<br>Follicular phase-based training five times a week during the follicular phase (the first two weeks of the menstrual cycle) and thereafter once a week for the rest of the cycle. | Other: Periodization of training<br>* Participants in the three arms will exercise the same dose and number of sessions distributed in three different ways.<br>| | Experimental: Luteal phase based training<br>Luteal phase-based training five times a week during the luteal phase (from ovulation to next menstruation) and once a week in the follicular phase. | Other: Periodization of training<br>* Participants in the three arms will exercise the same dose and number of sessions distributed in three different ways.<br>| | Experimental: Regular training<br>Regular training three times a week throughout the menstrual cycle (control group). | Other: Periodization of training<br>* Participants in the three arms will exercise the same dose and number of sessions distributed in three different ways.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in aerobic performance | Cosmeds K5 Wearable Metabolic System will be used for breath-by-breath gas exchange measurements. Change in VO2peak from baseline to end of study will be evaluated. | Change from baseline aerobic performance at the end of Cycle 4 (each cycle is around 28 days) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in muscle strength | A standardized isokinetic device (Biodex®, Corp, Shirley, NY, USA) will be used for measurements of maximal muscle torque (Nm) in the leg extensor muscles at 90 and 120 gr/sec (11). Change in muscle strength from baseline to end of study will be compared between groups. | Change from baseline muscle strength at the end of Cycle 4 (each cycle is around 28 days) | | Change in one-leg sit-to-stand test | Assessment of functional muscle strength in the lower extremities. | Change from baseline test at the end of Cycle 4 (each cycle is around 28 days) | | Change in one-leg hop test for distance | Assessment of functional muscle strength in the lower extremities. | Change from baseline test at the end of Cycle 4 (each cycle is around 28 days) | | Change in body composition | Differences in body fat (%) will be determined by DXA (Lunar equipment). | Change from baseline body composition at the end of Cycle 4 (each cycle is around 28 days) | | Change in body composition | Differences in muscle mass (g), will be determined by DXA (Lunar equipment). | Change from baseline body composition at the end of Cycle 4 (each cycle is around 28 days) | | Premenstrual symptoms | Prospective ratings of premenstrual symptoms will be performed with the Cyclicity Diagnoser | Every day during the study period | | Change in metabolic serum markers | Blood samples for analysis of IGF-1. | Change from baseline metabolic serum markers at the end of Cycle 4 (each cycle is around 28 days) | | Change in mucle morphology | Muscle biopsy in mm vastus lateralis | Change from baseline muscle morphology at the end of Cycle 4 (each cycle is around 28 days) | | Change in muscle tissue steroid hormones | Muscle biopsy in mm vastus lateralis | Change from baseline muscle tissue steroid hormones at the end of Cycle 4 (each cycle is around 28 days) | | Change in muscle protein synthesis | Muscle biopsy in mm vastus lateralis | Change from baseline muscle protein synthesis at the end of Cycle 4 (each cycle is around 28 days) | | Dysmenorrhea | Questionnaire | Through study completion, an average of 4 month | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Menstrual Cycle, Exercise, Women's Health, Athletic Performance

NCT01832168

Randomized Clinical Trial Using Amniotic Membrane in Robotic Assisted Laparoscopic Prostatectomy

The purpose of this study is to determine whether the AmnioFix dehydrated human amniotic membrane is effective in protecting nerves in men receiving robotic assisted laparoscopic prostatectomies.

A Prospective Randomized Clinical Trial Using Amniotic Membrane in Robotic Assisted Laparoscopic Prostatectomy (RALP)- Effect on Nerve Protection.

Pudendal Nerve

* Procedure: Robotic Assisted Laparoscopic Prostatectomy * Other: Application of Absorbable Hemostat * Other: Application of dehydrated human amniotic membrane

Inclusion Criteria:~Ages 45-70~Clinically localized prostate cancer with Gleason score 6 or 7~SHIM Score greater than or equal to 16 in the absence of medication~Feasibility to perform unilateral or bilateral nerve sparing RALP~Exclusion Criteria:~Clinically locally advanced cancer and/or with Gleason score 8 or 9.~Difficulty performing nerve sparing RALP.~Prior surgery at the site.~Site exhibits clinical signs and symptoms of infection.~SHIM score at screening <16.~Current use of anticoagulant medication including Coumadin, Plavix, etc.~Has had salvage prostatectomy - patients who failed prior therapies including external radiation therapy, cryotherapy, etc.~Has prior radiation therapy treatment at the site.~Prior hormonal therapy such as Lupron or oral anti-androgens.~Non-mobile, i.e. not ambulatory or bed ridden.~The presence of comorbidities that can be confused with or can exacerbate the condition including:~diabetes~advanced atherosclerotic vascular disease~Patients with a history of more than two weeks treatment with immuno-suppressants (including systemic corticosteroids), cytotoxic chemotherapy within one month prior to initial screening, or who receive such medications during the screening period, or who are anticipated to require such medications during the course of the study.~Patients on any investigational drug(s) or therapeutic device(s) within 30 days preceding screening.~Unable to comply with penile rehabilitation.~Known history of having Acquired Immunodeficiency Syndrome (AIDS) or HIV.~Patients who are unable to understand the aims and objectives of the trial.~Presence of any condition(s) which seriously compromises the subject's ability to complete this study, or has a known history of poor adherence with medical treatment.~Currently taking medications which could affect graft incorporation (supervising physician's discretion).~Allergic to gentamicin and/or streptomycin.~Damage to neurovascular bundles during surgery.

45 Years

70 Years

Male

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The proportion of patients achieving return to baseline Sexual Health Inventory for Men (SHIM) score in the AmnioFix group versus the Control group. | | 4 weeks |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Time to return of erectile function. | | Up to 6 months | | Pain scores. | | 10 days, 4 weeks, 3 months, and 6 months |

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: Control<br>Robotic Assisted Laparoscopic Prostatectomy with application of absorbable hemostat. | Procedure: Robotic Assisted Laparoscopic Prostatectomy<br>* Robotic Assisted Laparoscopic Prostatectomy with nerve-sparing technique<br>Other: Application of Absorbable Hemostat<br>* Application of Surgicel® SNoW Absorbable Hemostat by Johnson and Johnson on the neurovascular bundle after removal of the cancerous prostate.<br>* Other names: Surgicel® SNoW;| | Experimental: AmnioFix<br>Robotic Assisted Laparoscopic Prostatectomy with application of dehydrated human amniotic membrane. | Procedure: Robotic Assisted Laparoscopic Prostatectomy<br>* Robotic Assisted Laparoscopic Prostatectomy with nerve-sparing technique<br>Other: Application of dehydrated human amniotic membrane<br>* Application of dehydrated human amniotic membrane (DHAM) on the neurovascular bundle after removal of the cancerous prostate.<br>* Other names: AmnioFix;|

Randomized Clinical Trial Using Amniotic Membrane in Robotic Assisted Laparoscopic Prostatectomy Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine whether the AmnioFix dehydrated human amniotic membrane is effective in protecting nerves in men receiving robotic assisted laparoscopic prostatectomies. Official Title ----------------- A Prospective Randomized Clinical Trial Using Amniotic Membrane in Robotic Assisted Laparoscopic Prostatectomy (RALP)- Effect on Nerve Protection. Conditions ----------------- Pudendal Nerve Intervention / Treatment ----------------- * Procedure: Robotic Assisted Laparoscopic Prostatectomy * Other: Application of Absorbable Hemostat * Other: Application of dehydrated human amniotic membrane Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Ages 45-70 Clinically localized prostate cancer with Gleason score 6 or 7 SHIM Score greater than or equal to 16 in the absence of medication Feasibility to perform unilateral or bilateral nerve sparing RALP Exclusion Criteria: Clinically locally advanced cancer and/or with Gleason score 8 or 9. Difficulty performing nerve sparing RALP. Prior surgery at the site. Site exhibits clinical signs and symptoms of infection. SHIM score at screening <16. Current use of anticoagulant medication including Coumadin, Plavix, etc. Has had salvage prostatectomy - patients who failed prior therapies including external radiation therapy, cryotherapy, etc. Has prior radiation therapy treatment at the site. Prior hormonal therapy such as Lupron or oral anti-androgens. Non-mobile, i.e. not ambulatory or bed ridden. The presence of comorbidities that can be confused with or can exacerbate the condition including: diabetes advanced atherosclerotic vascular disease Patients with a history of more than two weeks treatment with immuno-suppressants (including systemic corticosteroids), cytotoxic chemotherapy within one month prior to initial screening, or who receive such medications during the screening period, or who are anticipated to require such medications during the course of the study. Patients on any investigational drug(s) or therapeutic device(s) within 30 days preceding screening. Unable to comply with penile rehabilitation. Known history of having Acquired Immunodeficiency Syndrome (AIDS) or HIV. Patients who are unable to understand the aims and objectives of the trial. Presence of any condition(s) which seriously compromises the subject's ability to complete this study, or has a known history of poor adherence with medical treatment. Currently taking medications which could affect graft incorporation (supervising physician's discretion). Allergic to gentamicin and/or streptomycin. Damage to neurovascular bundles during surgery. Ages Eligible for Study ----------------- Minimum Age: 45 Years Maximum Age: 70 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: Control<br>Robotic Assisted Laparoscopic Prostatectomy with application of absorbable hemostat. | Procedure: Robotic Assisted Laparoscopic Prostatectomy<br>* Robotic Assisted Laparoscopic Prostatectomy with nerve-sparing technique<br>Other: Application of Absorbable Hemostat<br>* Application of Surgicel® SNoW Absorbable Hemostat by Johnson and Johnson on the neurovascular bundle after removal of the cancerous prostate.<br>* Other names: Surgicel® SNoW;| | Experimental: AmnioFix<br>Robotic Assisted Laparoscopic Prostatectomy with application of dehydrated human amniotic membrane. | Procedure: Robotic Assisted Laparoscopic Prostatectomy<br>* Robotic Assisted Laparoscopic Prostatectomy with nerve-sparing technique<br>Other: Application of dehydrated human amniotic membrane<br>* Application of dehydrated human amniotic membrane (DHAM) on the neurovascular bundle after removal of the cancerous prostate.<br>* Other names: AmnioFix;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The proportion of patients achieving return to baseline Sexual Health Inventory for Men (SHIM) score in the AmnioFix group versus the Control group. | | 4 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Time to return of erectile function. | | Up to 6 months | | Pain scores. | | 10 days, 4 weeks, 3 months, and 6 months |

NCT00305812

Lenalidomide and Melphalan in Treating Patients With Previously Untreated Multiple Myeloma

RATIONALE: Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with melphalan may kill more cancer cells.~PURPOSE: This randomized phase II trial is studying the side effects and best dose of lenalidomide when given together with melphalan and to see how well they work in treating patients with multiple myeloma.

OBJECTIVES:~Primary~Evaluate the tolerability of 2 different doses of lenalidomide when administered with melphalan in patients with previously untreated multiple myeloma who are not planning to undergo future autologous stem cell transplantation.~Secondary~Characterize the toxicity profile of lenalidomide in combination with melphalan.~Determine tumor response in these patients after 2 and 12 courses of induction therapy with lenalidomide and melphalan and after 6 months of maintenance therapy with dexamethasone.~Determine progression-free and overall survival of these patients.~Determine time to dose modification and time to dose discontinuation in these patients.~Tertiary~Examine wnt pathway inhibition in response to lenalidomide on pre- and post-treatment bone marrow and blood samples using enzyme-linked immunosorbent assay (ELISA), gene expression profiling, drosophila-based chemical genetics, and surface-enhanced laser desorption/ionization mass spectrometry (SELDI MS) proteomics.~OUTLINE: This is a multicenter, randomized, open-label, dose-finding study of lenalidomide.~Prior to randomization, 6 patients receive oral lenalidomide at a lower dose (same dose to be used in arm I) once daily on days 1-21 and oral melphalan once daily on days 1-4. Treatment repeats every 28 days for 3 courses. If no unacceptable toxicity occurs, the trial will proceed and randomization will occur.~Induction therapy: Patients are randomized to 1 of 2 dose levels of lenalidomide.~Arm I: Patients receive oral lenalidomide once daily on days 1-21 and oral melphalan once daily on days 1-4.~Arm II: Patients receive oral lenalidomide as in arm I, but at a lower dose, and melphalan as in arm I, but at a higher dose.~Treatment in both arms repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After 12 courses of induction therapy, patients in both arms without progressive disease proceed to maintenance therapy.~Maintenance therapy: Patients receive oral dexamethasone once daily on days 1-4. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed at 4 weeks and then every 2 months thereafter.~PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.

A Randomized Phase II Dose Finding Study of Revlimid™ and Melphalan in Patients With Previously Untreated Multiple Myeloma

Multiple Myeloma and Plasma Cell Neoplasm

* Drug: dexamethasone * Drug: lenalidomide * Drug: melphalan

DISEASE CHARACTERISTICS:~Histologically confirmed multiple myeloma by one of the following:~Biopsy of an osteolytic lesion or soft tissue tumor composed of plasma cells~Bone marrow aspirate and/or biopsy demonstrating ≥ 10% plasmacytosis~Bone marrow < 10% plasma cells but with ≥ 1 bony lesion AND meets the M-protein criteria~Ineligible for stem cell transplantation due to any of the following:~Advanced age~Comorbid illness~Patient preference~Previously untreated disease~Measurable (i.e., quantifiable) serum M-component of IgG, IgA, IgD, or IgE at initial diagnosis OR, if only light-chain disease is present (urine M-protein only), urinary excretion of light-chain protein (Bence Jones) ≥ 1.0 g/24 hours at initial diagnosis~No nonsecretory myeloma~PATIENT CHARACTERISTICS:~ECOG performance status 0-2~Life expectancy ≥ 12 months~Absolute neutrophil count ≥ 1,500/mm^3~Platelet count ≥ 150,000/mm^3~Creatinine ≤ 3 times upper limit of normal (ULN)~Bilirubin ≤ 1.5 times ULN~AST and/or ALT ≤ 1.5 times ULN~Alkaline phosphatase ≤ 1.5 times ULN~Not pregnant or nursing~Negative pregnancy test~Fertile patients must use 2 methods of effective contraception during and for 4 weeks after completion of study treatment~No other malignancies within the past 5 years, except adequately treated nonmelanoma skin cancer or curatively treated in situ cancer of the cervix~No hypersensitivity to thalidomide or its components, including the development of a desquamating rash~No other serious illness or medical condition that would preclude study participation~No history of significant neurologic or psychiatric disorder that would preclude informed consent~No known HIV positivity~No pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction, including any of the following:~Significant cardiac event (including symptomatic heart failure or angina) within 3 months prior to randomization~Any cardiac disease that increases risk for ventricular arrhythmia~History of ventricular arrhythmia that was symptomatic or required treatment, including any of the following:~Multifocal premature ventricular contractions~Bigeminy~Trigeminy~Ventricular tachycardia/fibrillation/flutter/arrhythmia NOS~PRIOR CONCURRENT THERAPY:~No prior chemotherapy or corticosteroids for the treatment of multiple myeloma~Prior corticosteroids for the treatment of hypercalcemia or spinal cord compression allowed provided maximum levels have not been reached (i.e.,< 120 mg for dexamethasone or < 792 mg for prednisone)~Prior radiotherapy to single sites for pain control or local plasmacytoma allowed~Prior or concurrent bisphosphonates allowed~At least 28 days since prior investigational anticancer agents or therapy~No concurrent corticosteroids above physiologic replacement doses~Concurrent radiotherapy to sites of active myeloma with pain or neurologic compromise allowed~No concurrent filgrastim (G-CSF) on day 1 of course 1~No other concurrent anticancer therapy~No other concurrent investigational therapy

18 Years

120 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of dose-limiting toxicity within first 3 courses of treatment | | |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Toxicity | | | | Disease response after 2 courses, 6 courses, 12 courses, and 6 months of maintenance therapy | | | | Time to progression | | | | Overall survival | | | | Duration of disease-free interval | | | | Time to dose modification | | | | Time to dose discontinuation | | |

stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

Dexamethasone, Lenalidomide, Melphalan, Anti-Inflammatory Agents, Antiemetics, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Gastrointestinal Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Antineoplastic Agents, Hormonal, Antineoplastic Agents, Immunologic Factors, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Growth Inhibitors, Antineoplastic Agents, Alkylating, Alkylating Agents, Molecular Mechanisms of Pharmacological Action, Myeloablative Agonists, Immunosuppressive Agents

| Intervention/Treatment | | --- | |Drug: dexamethasone|nan| |Drug: lenalidomide|nan| |Drug: melphalan|nan|

Lenalidomide and Melphalan in Treating Patients With Previously Untreated Multiple Myeloma Study Overview ================= Brief Summary ----------------- RATIONALE: Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with melphalan may kill more cancer cells. PURPOSE: This randomized phase II trial is studying the side effects and best dose of lenalidomide when given together with melphalan and to see how well they work in treating patients with multiple myeloma. Detailed Description ----------------- OBJECTIVES: Primary Evaluate the tolerability of 2 different doses of lenalidomide when administered with melphalan in patients with previously untreated multiple myeloma who are not planning to undergo future autologous stem cell transplantation. Secondary Characterize the toxicity profile of lenalidomide in combination with melphalan. Determine tumor response in these patients after 2 and 12 courses of induction therapy with lenalidomide and melphalan and after 6 months of maintenance therapy with dexamethasone. Determine progression-free and overall survival of these patients. Determine time to dose modification and time to dose discontinuation in these patients. Tertiary Examine wnt pathway inhibition in response to lenalidomide on pre- and post-treatment bone marrow and blood samples using enzyme-linked immunosorbent assay (ELISA), gene expression profiling, drosophila-based chemical genetics, and surface-enhanced laser desorption/ionization mass spectrometry (SELDI MS) proteomics. OUTLINE: This is a multicenter, randomized, open-label, dose-finding study of lenalidomide. Prior to randomization, 6 patients receive oral lenalidomide at a lower dose (same dose to be used in arm I) once daily on days 1-21 and oral melphalan once daily on days 1-4. Treatment repeats every 28 days for 3 courses. If no unacceptable toxicity occurs, the trial will proceed and randomization will occur. Induction therapy: Patients are randomized to 1 of 2 dose levels of lenalidomide. Arm I: Patients receive oral lenalidomide once daily on days 1-21 and oral melphalan once daily on days 1-4. Arm II: Patients receive oral lenalidomide as in arm I, but at a lower dose, and melphalan as in arm I, but at a higher dose. Treatment in both arms repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After 12 courses of induction therapy, patients in both arms without progressive disease proceed to maintenance therapy. Maintenance therapy: Patients receive oral dexamethasone once daily on days 1-4. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 4 weeks and then every 2 months thereafter. PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study. Official Title ----------------- A Randomized Phase II Dose Finding Study of Revlimid™ and Melphalan in Patients With Previously Untreated Multiple Myeloma Conditions ----------------- Multiple Myeloma and Plasma Cell Neoplasm Intervention / Treatment ----------------- * Drug: dexamethasone * Drug: lenalidomide * Drug: melphalan Participation Criteria ================= Eligibility Criteria ----------------- DISEASE CHARACTERISTICS: Histologically confirmed multiple myeloma by one of the following: Biopsy of an osteolytic lesion or soft tissue tumor composed of plasma cells Bone marrow aspirate and/or biopsy demonstrating ≥ 10% plasmacytosis Bone marrow < 10% plasma cells but with ≥ 1 bony lesion AND meets the M-protein criteria Ineligible for stem cell transplantation due to any of the following: Advanced age Comorbid illness Patient preference Previously untreated disease Measurable (i.e., quantifiable) serum M-component of IgG, IgA, IgD, or IgE at initial diagnosis OR, if only light-chain disease is present (urine M-protein only), urinary excretion of light-chain protein (Bence Jones) ≥ 1.0 g/24 hours at initial diagnosis No nonsecretory myeloma PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 12 months Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 150,000/mm^3 Creatinine ≤ 3 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN AST and/or ALT ≤ 1.5 times ULN Alkaline phosphatase ≤ 1.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 methods of effective contraception during and for 4 weeks after completion of study treatment No other malignancies within the past 5 years, except adequately treated nonmelanoma skin cancer or curatively treated in situ cancer of the cervix No hypersensitivity to thalidomide or its components, including the development of a desquamating rash No other serious illness or medical condition that would preclude study participation No history of significant neurologic or psychiatric disorder that would preclude informed consent No known HIV positivity No pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction, including any of the following: Significant cardiac event (including symptomatic heart failure or angina) within 3 months prior to randomization Any cardiac disease that increases risk for ventricular arrhythmia History of ventricular arrhythmia that was symptomatic or required treatment, including any of the following: Multifocal premature ventricular contractions Bigeminy Trigeminy Ventricular tachycardia/fibrillation/flutter/arrhythmia NOS PRIOR CONCURRENT THERAPY: No prior chemotherapy or corticosteroids for the treatment of multiple myeloma Prior corticosteroids for the treatment of hypercalcemia or spinal cord compression allowed provided maximum levels have not been reached (i.e.,< 120 mg for dexamethasone or < 792 mg for prednisone) Prior radiotherapy to single sites for pain control or local plasmacytoma allowed Prior or concurrent bisphosphonates allowed At least 28 days since prior investigational anticancer agents or therapy No concurrent corticosteroids above physiologic replacement doses Concurrent radiotherapy to sites of active myeloma with pain or neurologic compromise allowed No concurrent filgrastim (G-CSF) on day 1 of course 1 No other concurrent anticancer therapy No other concurrent investigational therapy Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 120 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Intervention/Treatment | | --- | |Drug: dexamethasone|nan| |Drug: lenalidomide|nan| |Drug: melphalan|nan| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of dose-limiting toxicity within first 3 courses of treatment | | | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Toxicity | | | | Disease response after 2 courses, 6 courses, 12 courses, and 6 months of maintenance therapy | | | | Time to progression | | | | Overall survival | | | | Duration of disease-free interval | | | | Time to dose modification | | | | Time to dose discontinuation | | | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

NCT01708447

Feasibility Study: Evaluate the Effectiveness of Using a Topical Anesthetic Prior to Ultherapy™ Treatment

This study will evaluate the efficacy of a lidocaine topical anesthetic (numbing cream) for reducing discomfort associated with Ultherapy™ treatment.

All subjects will receive a full face and neck Ultherapy™ treatment. Thirty (30) minutes prior to treatment, a topical anesthetic (numbing cream) will be applied to one side of the face and neck and a placebo cream with similar consistency and color will be applied to the other side of the face and neck, in a randomized fashion. The subject and investigator or sub-investigator performing Ultherapy™ treatment will be blinded to the side to which the topical anesthetic is applied. Pain scores will be collected following treatment of each section of the face and neck on both sides. Subjects will return for a 90-day post-treatment visit to assess improvement in skin laxity, and overall lifting and tightening of skin.

Feasibility Study: Evaluation of the Efficacy of a Liposome-encapsulated Lidocaine Topical Anesthetic for Reducing Discomfort Associated With Ultherapy™ Treatment

Skin Laxity

* Drug: L.M.X.4.® cream * Other: A placebo cream * Device: Ulthera System Treatment

Inclusion Criteria:~Male or female, aged 30 to 65 years.~Chosen an Ultherapy™ treatment as part of their treatment regimen.~Subject in good health.~Skin laxity on the face and neck.~Understands and accepts the obligation not to undergo any other procedures in the areas to be treated through the followup period.~Willingness and ability to comply with protocol requirements, including returning for follow-up visits and abstaining from exclusionary procedures for the duration of the study~Exclusion Criteria:~Known sensitivity to lidocaine or any other anesthetic of the amide type.~History of anaphylactic shock.~Presence of an active systemic or local skin disease that may affect wound healing.~Current therapy with class I antiarrhythmic drugs (e.g., tocainide, mexiletine).~Known or suspected hypersensitivity to LMX-4 active substance, or any of the amide-type local anaesthetics, or any of the excipients (protocol section 10.3).~Severe solar elastosis.~Excessive subcutaneous fat in the face and neck.~Body mass index of 30 or greater.~Excessive skin laxity on the face and neck.~Significant scarring in areas to be treated.~Significant open facial wounds or lesions.~Severe or cystic acne on the face.~Presence of a metal stent or implant in the facial area to be treated.

30 Years

65 Years

All

Accepts Healthy Volunteers

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Single Group Assignment Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Treatment-related pain | The validated 10-point pain NRS scale will be used to measure average pain scores reported by subject immediately after each facial region is treated. | During treatment |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Improvement in skin laxity. | Improvement in overall lifting and tightening of skin as determined by a masked, qualitative assessment of photographs. | 90 days post-treatment |

Lidocaine, Anesthetics, Anesthetics, Local, Central Nervous System Depressants, Physiological Effects of Drugs, Sensory System Agents, Peripheral Nervous System Agents, Anti-Arrhythmia Agents, Voltage-Gated Sodium Channel Blockers, Sodium Channel Blockers, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Topical anesthetic - L.M.X.4.® cream<br>Topical anesthetic cream, L.M.X.4.® cream, applied to one side of the face and neck prior to Ulthera System treatment. | Drug: L.M.X.4.® cream<br>* A lidocaine topical anesthetic cream<br>* Other names: A lidocaine topical anesthetic cream;Device: Ulthera System Treatment<br>* Focused ultrasound energy delivered below the surface of the skin<br>* Other names: Ultrasound treatment for skin tightening;| | Placebo Comparator: Placebo cream<br>A placebo cream with similar consistency and color will be applied to the other side of the face and neck prior to Ulthera System treatment. | Other: A placebo cream<br>* Placebo cream containing no anesthetic properties.<br>Device: Ulthera System Treatment<br>* Focused ultrasound energy delivered below the surface of the skin<br>* Other names: Ultrasound treatment for skin tightening;|

Feasibility Study: Evaluate the Effectiveness of Using a Topical Anesthetic Prior to Ultherapy™ Treatment Study Overview ================= Brief Summary ----------------- This study will evaluate the efficacy of a lidocaine topical anesthetic (numbing cream) for reducing discomfort associated with Ultherapy™ treatment. Detailed Description ----------------- All subjects will receive a full face and neck Ultherapy™ treatment. Thirty (30) minutes prior to treatment, a topical anesthetic (numbing cream) will be applied to one side of the face and neck and a placebo cream with similar consistency and color will be applied to the other side of the face and neck, in a randomized fashion. The subject and investigator or sub-investigator performing Ultherapy™ treatment will be blinded to the side to which the topical anesthetic is applied. Pain scores will be collected following treatment of each section of the face and neck on both sides. Subjects will return for a 90-day post-treatment visit to assess improvement in skin laxity, and overall lifting and tightening of skin. Official Title ----------------- Feasibility Study: Evaluation of the Efficacy of a Liposome-encapsulated Lidocaine Topical Anesthetic for Reducing Discomfort Associated With Ultherapy™ Treatment Conditions ----------------- Skin Laxity Intervention / Treatment ----------------- * Drug: L.M.X.4.® cream * Other: A placebo cream * Device: Ulthera System Treatment Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male or female, aged 30 to 65 years. Chosen an Ultherapy™ treatment as part of their treatment regimen. Subject in good health. Skin laxity on the face and neck. Understands and accepts the obligation not to undergo any other procedures in the areas to be treated through the followup period. Willingness and ability to comply with protocol requirements, including returning for follow-up visits and abstaining from exclusionary procedures for the duration of the study Exclusion Criteria: Known sensitivity to lidocaine or any other anesthetic of the amide type. History of anaphylactic shock. Presence of an active systemic or local skin disease that may affect wound healing. Current therapy with class I antiarrhythmic drugs (e.g., tocainide, mexiletine). Known or suspected hypersensitivity to LMX-4 active substance, or any of the amide-type local anaesthetics, or any of the excipients (protocol section 10.3). Severe solar elastosis. Excessive subcutaneous fat in the face and neck. Body mass index of 30 or greater. Excessive skin laxity on the face and neck. Significant scarring in areas to be treated. Significant open facial wounds or lesions. Severe or cystic acne on the face. Presence of a metal stent or implant in the facial area to be treated. Ages Eligible for Study ----------------- Minimum Age: 30 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Single Group Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Topical anesthetic - L.M.X.4.® cream<br>Topical anesthetic cream, L.M.X.4.® cream, applied to one side of the face and neck prior to Ulthera System treatment. | Drug: L.M.X.4.® cream<br>* A lidocaine topical anesthetic cream<br>* Other names: A lidocaine topical anesthetic cream;Device: Ulthera System Treatment<br>* Focused ultrasound energy delivered below the surface of the skin<br>* Other names: Ultrasound treatment for skin tightening;| | Placebo Comparator: Placebo cream<br>A placebo cream with similar consistency and color will be applied to the other side of the face and neck prior to Ulthera System treatment. | Other: A placebo cream<br>* Placebo cream containing no anesthetic properties.<br>Device: Ulthera System Treatment<br>* Focused ultrasound energy delivered below the surface of the skin<br>* Other names: Ultrasound treatment for skin tightening;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Treatment-related pain | The validated 10-point pain NRS scale will be used to measure average pain scores reported by subject immediately after each facial region is treated. | During treatment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Improvement in skin laxity. | Improvement in overall lifting and tightening of skin as determined by a masked, qualitative assessment of photographs. | 90 days post-treatment |

NCT02172235

Relative Bioavailability of Pioglitazone After Co-administration With Different Doses of BI 10773 in Healthy Volunteers

The objective was to investigate the effect of different doses of BI 10773 on the bioavailability of pioglitazone after multiple oral doses of both drugs

Relative Bioavailability of Pioglitazone After Co-administration With Different Doses of BI 10773 in Healthy Volunteers (an Open-label, Randomised, Crossover, Clinical Phase I Study)

Healthy

* Drug: Pioglitazone * Drug: Pioglitazone - low dose * Drug: BI 10773 - low dose * Drug: BI 10773 - medium dose * Drug: BI 10773 - high dose

Inclusion Criteria:~Healthy male subjects according to the following criteria:~medical history, physical examination, vital signs ((blood pressure (BP), pulse rate (PR), 12-lead electrocardiogram (ECG)), clinical laboratory tests~Age 18 to 55 years (incl.)~BMI 18.5 to 29.9 kg/m2 (incl.)~Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practise (GCP) and the local legislation~Exclusion Criteria:~Any finding of the medical examination including blood pressure (BP), pulse rate (PR) and electrocardiogram (ECG) deviating from normal and of clinical relevance~Any evidence of a clinically relevant concomitant disease~Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders~Surgery of the gastrointestinal tract (except appendectomy)~Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders~History of relevant orthostatic hypotension, fainting spells or blackouts.~Chronic or relevant acute infections~History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)~Intake of drugs with a long half-life (more than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial~Participation in another trial with an investigational drug within two months prior to administration or during the trial~Smoker (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day)~Inability to refrain from smoking on trial days~Alcohol abuse (more than 30 g/day)~Drug abuse~Blood donation (more than 100 mL within four weeks prior to administration or during the trial)~Excessive physical activities (within one week prior to administration or during the trial)~Alanine aminotransferase (ALT) outside the normal range or any other laboratory value outside the reference range that is of clinical relevance~Inability to comply with dietary regimen of trial site~Galactose or lactose intolerance, galactose or glucose malabsorption

18 Years

55 Years

Male

Accepts Healthy Volunteers

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) | | Before each dosing, up to 10 days | | Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) | | Before each dosing, up to 10 days |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | C24,N (concentration of the analyte in plasma at 24 h after administration of the Nth dose) | | Before each dosing, up to 10 days | | λz (terminal elimination rate constant of the analyte in plasma) | | Before each dosing, up to 10 days | | t½ (terminal half-life of the analyte in plasma) | | Before each dosing, up to 10 days | | tmax (time from last dosing to maximum measured concentration of the analyte in plasma) | | Before each dosing, up to 10 days | | MRTpo (mean residence time of the analyte in the body at steady state after oral administration) | | Before each dosing, up to 10 days | | CL/F (apparent clearance of the analyte in the plasma after extravascular administration) | | Before each dosing, up to 10 days | | Vz/F (apparent volume of distribution during the terminal phase λz following extravascular administration) | | Before each dosing, up to 10 days | | Aet1-t2 (amount of analyte eliminated in urine over the time interval t1 to t2 ) | | Day1 (-1-0, 0-4, 4-8, 8-12, and 12-24 h), Day 7 (143-144, 144-148, 148-152, 152-156, and 156-168 h) | | fet1-t2 (fraction of dose excreted unchanged in urine over the time interval t1 to t2) | | Day1 (-1-0, 0-4, 4-8, 8-12, and 12-24 h), Day 7 (143-144, 144-148, 148-152, 152-156, and 156-168 h) | | CLR (renal clearance of the analyte in plasma afer extravascular administration) | | Day1 (-1-0, 0-4, 4-8, 8-12, and 12-24 h), Day 7 (143-144, 144-148, 148-152, 152-156, and 156-168 h) | | Cmax (maximum concentration of the analyte in plasma) | | Before each dosing, up to 10 days | | AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable plasma concentration) | | Before each dosing, up to 10 days | | AUCτ,1 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable plasma concentration within the first dosing interval) | | Before each dosing, up to 10 days | | AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) | | Before each dosing, up to 10 days | | Metabolite to parent ratio | | Before each dosing, up to 10 days | | Number of patients with abnormal findings in physical examination | | up to 30 days after drug administration | | Number of patients with abnormal changes in laboratory parameters | | up to 30 days after drug administration | | Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG) | | up to 30 days after drug administration | | Number of patients with clinically significant changes in vital signs | | up to 30 days after drug administration | | Assessment of tolerability by investigator on a 4-point scale | | up to 10 days | | Number of patients with adverse events | | up to 51 days |

Pioglitazone, Empagliflozin, Hypoglycemic Agents, Physiological Effects of Drugs, Sodium-Glucose Transporter 2 Inhibitors, Molecular Mechanisms of Pharmacological Action

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Pioglitazone<br> | Drug: Pioglitazone<br> <br> | | Experimental: Pioglitazone + BI 10773 low<br> | Drug: Pioglitazone<br> <br> Drug: BI 10773 - low dose<br> <br> | | Experimental: Pioglitazone + BI 10773 medium<br> | Drug: Pioglitazone<br> <br> Drug: BI 10773 - medium dose<br> <br> | | Experimental: Pioglitazone + BI 10773 high<br> | Drug: Pioglitazone<br> <br> Drug: BI 10773 - high dose<br> <br> | | Experimental: Pioglitazone low + BI 10773 medium<br> | Drug: Pioglitazone - low dose<br> <br> Drug: BI 10773 - medium dose<br> <br> | | Experimental: Pioglitazone + BI 10773 1 hour after Pioglitazone<br> | Drug: Pioglitazone<br> <br> Drug: BI 10773 - medium dose<br> <br> |

Relative Bioavailability of Pioglitazone After Co-administration With Different Doses of BI 10773 in Healthy Volunteers Study Overview ================= Brief Summary ----------------- The objective was to investigate the effect of different doses of BI 10773 on the bioavailability of pioglitazone after multiple oral doses of both drugs Official Title ----------------- Relative Bioavailability of Pioglitazone After Co-administration With Different Doses of BI 10773 in Healthy Volunteers (an Open-label, Randomised, Crossover, Clinical Phase I Study) Conditions ----------------- Healthy Intervention / Treatment ----------------- * Drug: Pioglitazone * Drug: Pioglitazone - low dose * Drug: BI 10773 - low dose * Drug: BI 10773 - medium dose * Drug: BI 10773 - high dose Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Healthy male subjects according to the following criteria: medical history, physical examination, vital signs ((blood pressure (BP), pulse rate (PR), 12-lead electrocardiogram (ECG)), clinical laboratory tests Age 18 to 55 years (incl.) BMI 18.5 to 29.9 kg/m2 (incl.) Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practise (GCP) and the local legislation Exclusion Criteria: Any finding of the medical examination including blood pressure (BP), pulse rate (PR) and electrocardiogram (ECG) deviating from normal and of clinical relevance Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts. Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) Intake of drugs with a long half-life (more than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (more than 30 g/day) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within one week prior to administration or during the trial) Alanine aminotransferase (ALT) outside the normal range or any other laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of trial site Galactose or lactose intolerance, galactose or glucose malabsorption Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 55 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Pioglitazone<br> | Drug: Pioglitazone<br> <br> | | Experimental: Pioglitazone + BI 10773 low<br> | Drug: Pioglitazone<br> <br> Drug: BI 10773 - low dose<br> <br> | | Experimental: Pioglitazone + BI 10773 medium<br> | Drug: Pioglitazone<br> <br> Drug: BI 10773 - medium dose<br> <br> | | Experimental: Pioglitazone + BI 10773 high<br> | Drug: Pioglitazone<br> <br> Drug: BI 10773 - high dose<br> <br> | | Experimental: Pioglitazone low + BI 10773 medium<br> | Drug: Pioglitazone - low dose<br> <br> Drug: BI 10773 - medium dose<br> <br> | | Experimental: Pioglitazone + BI 10773 1 hour after Pioglitazone<br> | Drug: Pioglitazone<br> <br> Drug: BI 10773 - medium dose<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) | | Before each dosing, up to 10 days | | Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) | | Before each dosing, up to 10 days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | C24,N (concentration of the analyte in plasma at 24 h after administration of the Nth dose) | | Before each dosing, up to 10 days | | λz (terminal elimination rate constant of the analyte in plasma) | | Before each dosing, up to 10 days | | t½ (terminal half-life of the analyte in plasma) | | Before each dosing, up to 10 days | | tmax (time from last dosing to maximum measured concentration of the analyte in plasma) | | Before each dosing, up to 10 days | | MRTpo (mean residence time of the analyte in the body at steady state after oral administration) | | Before each dosing, up to 10 days | | CL/F (apparent clearance of the analyte in the plasma after extravascular administration) | | Before each dosing, up to 10 days | | Vz/F (apparent volume of distribution during the terminal phase λz following extravascular administration) | | Before each dosing, up to 10 days | | Aet1-t2 (amount of analyte eliminated in urine over the time interval t1 to t2 ) | | Day1 (-1-0, 0-4, 4-8, 8-12, and 12-24 h), Day 7 (143-144, 144-148, 148-152, 152-156, and 156-168 h) | | fet1-t2 (fraction of dose excreted unchanged in urine over the time interval t1 to t2) | | Day1 (-1-0, 0-4, 4-8, 8-12, and 12-24 h), Day 7 (143-144, 144-148, 148-152, 152-156, and 156-168 h) | | CLR (renal clearance of the analyte in plasma afer extravascular administration) | | Day1 (-1-0, 0-4, 4-8, 8-12, and 12-24 h), Day 7 (143-144, 144-148, 148-152, 152-156, and 156-168 h) | | Cmax (maximum concentration of the analyte in plasma) | | Before each dosing, up to 10 days | | AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable plasma concentration) | | Before each dosing, up to 10 days | | AUCτ,1 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable plasma concentration within the first dosing interval) | | Before each dosing, up to 10 days | | AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) | | Before each dosing, up to 10 days | | Metabolite to parent ratio | | Before each dosing, up to 10 days | | Number of patients with abnormal findings in physical examination | | up to 30 days after drug administration | | Number of patients with abnormal changes in laboratory parameters | | up to 30 days after drug administration | | Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG) | | up to 30 days after drug administration | | Number of patients with clinically significant changes in vital signs | | up to 30 days after drug administration | | Assessment of tolerability by investigator on a 4-point scale | | up to 10 days | | Number of patients with adverse events | | up to 51 days |

NCT01623791

Random Urine Protein-creatinin Ratio to Predict Magnitude of Proteinuria

The aim of this study was to evaluate diagnostic accuracy of the spot urinary proteinuria, random urine protein- creatinin ratio for prediction of significant proteinuria (≥ 300 mg/24h) and magnitude of proteinuria in patients with in mild preeclampsia and severe preeclampsia. The cross-sectional longitudinal study design used, 209 patients with pre-diagnosed preeclampsia in which in our inpatients clinic included this study. Random urine samples were taken before the 24 hour urine collection for spot urine analysis for evaluated proteinuria and protein/creatinin ratio. 24 hour urine analysis was performed in all patients as the gold standard of the urine total proteinuria.

Group 1 consisted of mild preeclampsia and gestational preeclamptic patients and group 2 consisted of severe preeclamptic patients. The predictive values of the spot urinary dipstick proteinuria and protein/creatinin ratio were determinant and the correlations of the diagnostic test of 24 hour total proteinuria were evaluated. The correlations of the severity of the disease and the tests of the proteinuria were evaluated.

Random Urine Protein-creatinine Ratio to Predict Magnitude of Proteinuria in Different Severity of Pre-eclamptic Patients

Pre-eclampsia

Inclusion Criteria:~16-50 years old, > 20 gestational week pregnant women pre-diagnosed preeclampsia.~Diagnosis and follow-up performed in inpatients clinic.~Exclusion Criteria:~The history of chronic hypertension~The history of systemic illness such as pre-gestational diabetes, systemic lupus erythematosis , malignancies, renal disease.~Pre-existing urinary tract infections~Premature rupture of membranes~Patients who have previously been enrolled in the study

16 Years

50 Years

Female

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Prediction of significant proteinuria | Significant proteiuria:(≥ 300 mg/24h) | 24 hour urine collection |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Predict to magnitude of total proteinuria | Total proteinuria/24 hour | 24 hour |

Pre-eclampsia, Proteinuria, Protein - creatinine ratio, Dipstick proteinuria, Severity of disease

Eclampsia, Proteinuria, Pre-Eclampsia, Hypertension, Pregnancy-Induced, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Urination Disorders, Urologic Diseases, Female Urogenital Diseases, Male Urogenital Diseases, Urological Manifestations

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Group 1<br>Group 1: mild pre-eclamptic group Mild and severe pre-eclampsia were defined American College of Obstetrics and Gynecology criteria (ACOG practice bulletin no. 33: diagnosis and management of preeclampsia and eclampsia. January 2002.) | | | Group 2<br>Group 2: severe pre-eclamptic group | |

Random Urine Protein-creatinin Ratio to Predict Magnitude of Proteinuria Study Overview ================= Brief Summary ----------------- The aim of this study was to evaluate diagnostic accuracy of the spot urinary proteinuria, random urine protein- creatinin ratio for prediction of significant proteinuria (≥ 300 mg/24h) and magnitude of proteinuria in patients with in mild preeclampsia and severe preeclampsia. The cross-sectional longitudinal study design used, 209 patients with pre-diagnosed preeclampsia in which in our inpatients clinic included this study. Random urine samples were taken before the 24 hour urine collection for spot urine analysis for evaluated proteinuria and protein/creatinin ratio. 24 hour urine analysis was performed in all patients as the gold standard of the urine total proteinuria. Detailed Description ----------------- Group 1 consisted of mild preeclampsia and gestational preeclamptic patients and group 2 consisted of severe preeclamptic patients. The predictive values of the spot urinary dipstick proteinuria and protein/creatinin ratio were determinant and the correlations of the diagnostic test of 24 hour total proteinuria were evaluated. The correlations of the severity of the disease and the tests of the proteinuria were evaluated. Official Title ----------------- Random Urine Protein-creatinine Ratio to Predict Magnitude of Proteinuria in Different Severity of Pre-eclamptic Patients Conditions ----------------- Pre-eclampsia Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 16-50 years old, > 20 gestational week pregnant women pre-diagnosed preeclampsia. Diagnosis and follow-up performed in inpatients clinic. Exclusion Criteria: The history of chronic hypertension The history of systemic illness such as pre-gestational diabetes, systemic lupus erythematosis , malignancies, renal disease. Pre-existing urinary tract infections Premature rupture of membranes Patients who have previously been enrolled in the study Ages Eligible for Study ----------------- Minimum Age: 16 Years Maximum Age: 50 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Group 1<br>Group 1: mild pre-eclamptic group Mild and severe pre-eclampsia were defined American College of Obstetrics and Gynecology criteria (ACOG practice bulletin no. 33: diagnosis and management of preeclampsia and eclampsia. January 2002.) | | | Group 2<br>Group 2: severe pre-eclamptic group | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Prediction of significant proteinuria | Significant proteiuria:(≥ 300 mg/24h) | 24 hour urine collection | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Predict to magnitude of total proteinuria | Total proteinuria/24 hour | 24 hour | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Pre-eclampsia, Proteinuria, Protein - creatinine ratio, Dipstick proteinuria, Severity of disease

NCT04112550

Clinical Effectiveness of Pre-operative Methadone in Single Level Lateral Transpsoas Interbody Fusions

Spinal operations including lumbar fusions for degenerative disorders are becoming more prevalent as the population ages. Inadequate or excessive postoperative analgesia can result in medical comorbidities and prolonged hospital length of stay and patient dissatisfaction.~Existing literature has highlighted the preoperative administration of methadone as a promising adjuvant for post operative pain control. Methadone has the benefit of being long-acting and has more stable serum concentration and a single preoperative dose may have significant benefits post operatively.~Here the investigators propose a prospective parallel-group, randomized, double-blinded study to assess post operative analgesic requirements after preoperative administration of either methadone 15 mg or Oxycodone 10/325. Primary outcome will be total IV and PO narcotic consumption in the post operative course. Secondary outcomes examined will include time to mobility, need for specialist pain management consultation, early readmission (within 2 weeks) for inadequate pain control, and complications associated with administration.

Lumbar spinal fusions are becoming increasingly popular and prevalent in the treatment of a variety of spinal pathologies, but predominantly for degenerative disease which is most prevalent in the obese and or older population. These operations can result in relatively high post operative surgical pain and necessitate significant post operative opioid consumption which can precipitate co-morbid medical conditions such as respiratory depression and failure, pneumonia, gastrointestinal ileus, deep venous thrombosis, and pulmonary embolism. Additionally, these medical comorbidities also represent an increased burden on healthcare expenditure with increased length of hospital stay, inpatient testing and treatment, and need for additional follow up.~The investigators objective is to study the effect of a long term opioid analgesic, methadone, in a uniform population undergoing a single level minimally invasive lumbar fusion. The preoperative single dose administration of methadone has already been shown to be effective in improving post operative pain control in open multi-level spinal fusion patient populations and has become the standard of care in most surgical centers across the country. The long half-life of methadone results in improved steady state pharmacokinetics relative to other traditional opioids and is thought to improve pain control while decreasing consumption. In addition to Mu opioid receptor agonism, Methadone is thought to also have adjunctive analgesic and anti-tolerance effects due to CNS excitatory glutamatergic NMDA receptor antagonism. There are also reports of synergistic effects from serotonin and norepinephrine reuptake inhibition.~The investigators predict that a single preoperative oral methadone administration can result in improved postoperative analgesia with requirement of less IV and PO traditional narcotics within the first 2 weeks post operatively and also will not increase co-morbid risks relative to traditional shorter acting opioid analgesics that are presently given preoperatively.

Clinical Effectiveness of Pre-operative Methadone in Single Level Lateral Transpsoas Interbody Fusions: A Randomized, Double-blinded, Controlled Trial

Degenerative Disc Disease, Spondylolisthesis, Lumbar Region

* Drug: Methadone Hydrochloride * Drug: Oxycodone-Acetaminophen

Inclusion Criteria:~Age: 18 - 70~Will undergo one level minimally invasive lumbar fusion surgery~Primary symptoms are back and/or leg pain~Exclusion Criteria:~Preoperative chronic renal insufficiency or failure (defined as a serum creatinine more than 2 mg/dl)~Significant liver disease (cirrhosis or hepatic failure)~American Society of Anesthesiologists (ASA) physical status IV or V~Pulmonary disease necessitating home oxygen therapy~Patients with acute bronchial asthma or hypercarbia~Patient who has or is suspected of having a paralytic ileus~Preoperative use of methadone or hydromorphone~Known hypersensitivity to methadone~Known hypersensitivity to oxycodone~Recent history of opioid or alcohol abuse~Inability to use a PCA device~Inability to speak English~Any patient judged by the anesthesia care team to potentially require prolonged postoperative intubation~Participation in another clinical trial~Inability of patient to provide study informed consent (including patients who are cognitively impaired)~Presence of drug interaction between methadone/oxycodone and patient's regular or PRN medications

18 Years

70 Years

All

Accepts Healthy Volunteers

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Post-operative in-hospital patient's narcotic requirement | The total Morphine Milligram Equivalent (MME) for each post-operative day | Post-operative day 0 to 4 | | Improvement in low back pain between the two cohorts as assessed by Oswestry Disbility Index (ODI) | Change in ODI (scale from 0 to 100) from pre-op to post-op (14 days post-op) | 14 days |

lateral lumbar interbody fusion, minimally invasive spinal surgery

Acetaminophen, Acetaminophen, hydrocodone drug combination, Oxycodone, Methadone, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Antipyretics, Analgesics, Opioid, Narcotics, Central Nervous System Depressants, Antitussive Agents, Respiratory System Agents, Anti-Inflammatory Agents, Non-Steroidal, Anti-Inflammatory Agents, Antirheumatic Agents

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Methadone<br>This cohort will receive oral methadone 15mg po tablet pre-operatively | Drug: Methadone Hydrochloride<br>* FDA approved medication to treat pain<br>| | Active Comparator: Oxycodone<br>This cohort will receive oxycodone/acetaminophen 10/325 po tablet pre-operatively | Drug: Oxycodone-Acetaminophen<br>* FDA approved medication to treat pain<br>|

Clinical Effectiveness of Pre-operative Methadone in Single Level Lateral Transpsoas Interbody Fusions Study Overview ================= Brief Summary ----------------- Spinal operations including lumbar fusions for degenerative disorders are becoming more prevalent as the population ages. Inadequate or excessive postoperative analgesia can result in medical comorbidities and prolonged hospital length of stay and patient dissatisfaction. Existing literature has highlighted the preoperative administration of methadone as a promising adjuvant for post operative pain control. Methadone has the benefit of being long-acting and has more stable serum concentration and a single preoperative dose may have significant benefits post operatively. Here the investigators propose a prospective parallel-group, randomized, double-blinded study to assess post operative analgesic requirements after preoperative administration of either methadone 15 mg or Oxycodone 10/325. Primary outcome will be total IV and PO narcotic consumption in the post operative course. Secondary outcomes examined will include time to mobility, need for specialist pain management consultation, early readmission (within 2 weeks) for inadequate pain control, and complications associated with administration. Detailed Description ----------------- Lumbar spinal fusions are becoming increasingly popular and prevalent in the treatment of a variety of spinal pathologies, but predominantly for degenerative disease which is most prevalent in the obese and or older population. These operations can result in relatively high post operative surgical pain and necessitate significant post operative opioid consumption which can precipitate co-morbid medical conditions such as respiratory depression and failure, pneumonia, gastrointestinal ileus, deep venous thrombosis, and pulmonary embolism. Additionally, these medical comorbidities also represent an increased burden on healthcare expenditure with increased length of hospital stay, inpatient testing and treatment, and need for additional follow up. The investigators objective is to study the effect of a long term opioid analgesic, methadone, in a uniform population undergoing a single level minimally invasive lumbar fusion. The preoperative single dose administration of methadone has already been shown to be effective in improving post operative pain control in open multi-level spinal fusion patient populations and has become the standard of care in most surgical centers across the country. The long half-life of methadone results in improved steady state pharmacokinetics relative to other traditional opioids and is thought to improve pain control while decreasing consumption. In addition to Mu opioid receptor agonism, Methadone is thought to also have adjunctive analgesic and anti-tolerance effects due to CNS excitatory glutamatergic NMDA receptor antagonism. There are also reports of synergistic effects from serotonin and norepinephrine reuptake inhibition. The investigators predict that a single preoperative oral methadone administration can result in improved postoperative analgesia with requirement of less IV and PO traditional narcotics within the first 2 weeks post operatively and also will not increase co-morbid risks relative to traditional shorter acting opioid analgesics that are presently given preoperatively. Official Title ----------------- Clinical Effectiveness of Pre-operative Methadone in Single Level Lateral Transpsoas Interbody Fusions: A Randomized, Double-blinded, Controlled Trial Conditions ----------------- Degenerative Disc Disease, Spondylolisthesis, Lumbar Region Intervention / Treatment ----------------- * Drug: Methadone Hydrochloride * Drug: Oxycodone-Acetaminophen Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age: 18 - 70 Will undergo one level minimally invasive lumbar fusion surgery Primary symptoms are back and/or leg pain Exclusion Criteria: Preoperative chronic renal insufficiency or failure (defined as a serum creatinine more than 2 mg/dl) Significant liver disease (cirrhosis or hepatic failure) American Society of Anesthesiologists (ASA) physical status IV or V Pulmonary disease necessitating home oxygen therapy Patients with acute bronchial asthma or hypercarbia Patient who has or is suspected of having a paralytic ileus Preoperative use of methadone or hydromorphone Known hypersensitivity to methadone Known hypersensitivity to oxycodone Recent history of opioid or alcohol abuse Inability to use a PCA device Inability to speak English Any patient judged by the anesthesia care team to potentially require prolonged postoperative intubation Participation in another clinical trial Inability of patient to provide study informed consent (including patients who are cognitively impaired) Presence of drug interaction between methadone/oxycodone and patient's regular or PRN medications Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 70 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Methadone<br>This cohort will receive oral methadone 15mg po tablet pre-operatively | Drug: Methadone Hydrochloride<br>* FDA approved medication to treat pain<br>| | Active Comparator: Oxycodone<br>This cohort will receive oxycodone/acetaminophen 10/325 po tablet pre-operatively | Drug: Oxycodone-Acetaminophen<br>* FDA approved medication to treat pain<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Post-operative in-hospital patient's narcotic requirement | The total Morphine Milligram Equivalent (MME) for each post-operative day | Post-operative day 0 to 4 | | Improvement in low back pain between the two cohorts as assessed by Oswestry Disbility Index (ODI) | Change in ODI (scale from 0 to 100) from pre-op to post-op (14 days post-op) | 14 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- lateral lumbar interbody fusion, minimally invasive spinal surgery

NCT02280551

The Australian Parental Supply of Alcohol Longitudinal Study (APSALS)

Parents can positively influence their children's alcohol use. One strategy they use is to provide their children with alcohol, believing it is the best way to teach their children how to drink responsibly. The impact of parental supply is not well understood and may be unintentionally harmful. This study will research the consequences of parental supply within the broader context of parent, child and peer relationships. It will help to determine how parental supply influences the different patterns of adolescent alcohol consumption over time, providing essential information to help parents prevent alcohol misuse in their children. Parents can play a pivotal role in prevention of alcohol misuse, but at present we don't know exactly how.

Title: The Australian Parental Supply of Alcohol Longitudinal Study (APSALS): Can parents teach their children to drink alcohol responsibly? Or, is one drop a drop too many?~Background: The Australian Parental Supply of Alcohol Longitudinal Study (APSALS) was established to investigate the short- and long-term associations between exposure to parental alcohol provision, early adolescent alcohol initiation, subsequent alcohol use, and alcohol-related harms, controlling for a wide range of parental, child, familial, peer, and contextual covariates. The cohort commenced with 1927 parent-child dyads comprised of Australian Grade 7 school students, and a parent/guardian. Baseline, one- and two-year follow-up data have been collected, and a three-year follow-up is underway. The data collected include child, familial, parental, and peer factors addressing demographics, alcohol use and supply, parenting practices, other substance use, adolescent behaviours, and peer influences. Baseline data show that only 5.8% of the Grade 7 adolescents had initiated alcohol consumption (of a whole serve of alcohol). Thus, the cohort is ideal for prospectively examining predictors of initiation and progression of alcohol use, which increases markedly through adolescence. Results to date have highlighted the importance of distinguishing between sipping and drinking of full serves of alcohol in the measurement of adolescent alcohol use as these represent distinct behaviours which occur in different environments.~Aims: The aims of this study are to determine if:~Parental supply is associated with the progression (acceleration/deceleration) in adolescent drinking over time;~The immediate and broader contextual factors mediate or moderate the relationship between parental supply and progression in adolescent drinking over time.~Design: A longitudinal study across three states in Australia (New South Wales, Tasmania, and Western Australia).~Recruitment: Catholic, Independent and Government school in NSW, Tasmania and Western Australia.~Data analysis: Logistic and binomial regression, and multi-level modelling will be used, and latent growth curve modelling (LGCM) within the framework of structural equations modelling (SEM). Moderating and mediating variables, both time variant (e.g., association with alcohol using peers) and time-invariant (e.g. gender) will be modelled. Outcome variables will be modelled using appropriate parametric distributions - Poisson distributions for count data outcomes and binomial distributions for categorical data outcomes. All analyses will be conducted in MPlus v5.2 or Stata. As recommended by Graham imputation of missing data will be done.~Sample size calculations: Due to the flexibility of the modelling approach taken (i.e., the number of parameters allowed to vary), there are a number of different scenarios that can be tested to determine an adequate sample size. The primary interest is in differences in drinking over time between groups who were supplied or not supplied alcohol. Thus, regression analysis will address drinking on a dummy-coded parental supply variable. It is hypothesised that parental supply of alcohol would alter the trajectory of harmful drinking by a regression coefficient of ±0.2. This regression coefficient is equivalent to a medium effect size difference between groups, a result which is not unexpected given past research. It was assumed that attrition would result in around 20% missing data on each subsequent measurement occasion. Based on simulation studies, and factoring in potential mediators and moderators, 600 children are required at a minimum. However, as small cell sizes for some associations may affect power, a final sample of ~1800 children and parents has been recruited.

The Australian Parental Supply of Alcohol Longitudinal Study (APSALS)

Alcohol Abuse

Inclusion Criteria:~Grade 7 High School enrolment~Parental signed informed consent provided~Exclusion Criteria:~none

11 Years

13 Years

All

Accepts Healthy Volunteers

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Frequency of alcohol consumption | Frequency of alcohol consumption within past 12 months, categorized as: none, 1 day/month, 2-3 days/month, 1 day/week, 2 days/week, 3 days/week, 4 days/week, 5 days/week, 6 days/week, every day. | 12 month | | Typical quantity of alcohol consumption | Quantity of alcohol consumption within past 12 months measured as number of standard drinks (an Australian standard drink contains 10g alcohol). | 12 month | | Frequency of binge drinking | Frequency of drinking more than 4 standard drinks in the past 12 months | 12 month | | Experience of alcohol related harms | 17 item scale of alcohol related harms, adapted from the School Health and Alcohol Harm Reduction Project. Scores range from 0 to 85, with higher scores indicating greater experience of harms. | 12 months | | Symptoms of alcohol abuse, dependence and alcohol use disorder | Symptoms of alcohol abuse, dependence, and alcohol use disorder measured via the Diagnostic Interview Schedule for Children 4th Edition. Items correspond to Diagnostic and Statistical Manual of Mental Disorders 4th Edition symptoms of alcohol abuse (4 symptoms), dependence (7 symptoms), and alcohol use disorder (11 symptoms). | 12 months |

adolescent, alcohol, parent, epidemiology

Alcoholism, Alcohol-Related Disorders, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Adolescents<br>1927 Grade 7 high school students | | | Parent<br>A parent of each of the 1927 Grade 7 high school students | |

The Australian Parental Supply of Alcohol Longitudinal Study (APSALS) Study Overview ================= Brief Summary ----------------- Parents can positively influence their children's alcohol use. One strategy they use is to provide their children with alcohol, believing it is the best way to teach their children how to drink responsibly. The impact of parental supply is not well understood and may be unintentionally harmful. This study will research the consequences of parental supply within the broader context of parent, child and peer relationships. It will help to determine how parental supply influences the different patterns of adolescent alcohol consumption over time, providing essential information to help parents prevent alcohol misuse in their children. Parents can play a pivotal role in prevention of alcohol misuse, but at present we don't know exactly how. Detailed Description ----------------- Title: The Australian Parental Supply of Alcohol Longitudinal Study (APSALS): Can parents teach their children to drink alcohol responsibly? Or, is one drop a drop too many? Background: The Australian Parental Supply of Alcohol Longitudinal Study (APSALS) was established to investigate the short- and long-term associations between exposure to parental alcohol provision, early adolescent alcohol initiation, subsequent alcohol use, and alcohol-related harms, controlling for a wide range of parental, child, familial, peer, and contextual covariates. The cohort commenced with 1927 parent-child dyads comprised of Australian Grade 7 school students, and a parent/guardian. Baseline, one- and two-year follow-up data have been collected, and a three-year follow-up is underway. The data collected include child, familial, parental, and peer factors addressing demographics, alcohol use and supply, parenting practices, other substance use, adolescent behaviours, and peer influences. Baseline data show that only 5.8% of the Grade 7 adolescents had initiated alcohol consumption (of a whole serve of alcohol). Thus, the cohort is ideal for prospectively examining predictors of initiation and progression of alcohol use, which increases markedly through adolescence. Results to date have highlighted the importance of distinguishing between sipping and drinking of full serves of alcohol in the measurement of adolescent alcohol use as these represent distinct behaviours which occur in different environments. Aims: The aims of this study are to determine if: Parental supply is associated with the progression (acceleration/deceleration) in adolescent drinking over time; The immediate and broader contextual factors mediate or moderate the relationship between parental supply and progression in adolescent drinking over time. Design: A longitudinal study across three states in Australia (New South Wales, Tasmania, and Western Australia). Recruitment: Catholic, Independent and Government school in NSW, Tasmania and Western Australia. Data analysis: Logistic and binomial regression, and multi-level modelling will be used, and latent growth curve modelling (LGCM) within the framework of structural equations modelling (SEM). Moderating and mediating variables, both time variant (e.g., association with alcohol using peers) and time-invariant (e.g. gender) will be modelled. Outcome variables will be modelled using appropriate parametric distributions - Poisson distributions for count data outcomes and binomial distributions for categorical data outcomes. All analyses will be conducted in MPlus v5.2 or Stata. As recommended by Graham imputation of missing data will be done. Sample size calculations: Due to the flexibility of the modelling approach taken (i.e., the number of parameters allowed to vary), there are a number of different scenarios that can be tested to determine an adequate sample size. The primary interest is in differences in drinking over time between groups who were supplied or not supplied alcohol. Thus, regression analysis will address drinking on a dummy-coded parental supply variable. It is hypothesised that parental supply of alcohol would alter the trajectory of harmful drinking by a regression coefficient of ±0.2. This regression coefficient is equivalent to a medium effect size difference between groups, a result which is not unexpected given past research. It was assumed that attrition would result in around 20% missing data on each subsequent measurement occasion. Based on simulation studies, and factoring in potential mediators and moderators, 600 children are required at a minimum. However, as small cell sizes for some associations may affect power, a final sample of 1800 children and parents has been recruited. Official Title ----------------- The Australian Parental Supply of Alcohol Longitudinal Study (APSALS) Conditions ----------------- Alcohol Abuse Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Grade 7 High School enrolment Parental signed informed consent provided Exclusion Criteria: none Ages Eligible for Study ----------------- Minimum Age: 11 Years Maximum Age: 13 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Adolescents<br>1927 Grade 7 high school students | | | Parent<br>A parent of each of the 1927 Grade 7 high school students | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Frequency of alcohol consumption | Frequency of alcohol consumption within past 12 months, categorized as: none, 1 day/month, 2-3 days/month, 1 day/week, 2 days/week, 3 days/week, 4 days/week, 5 days/week, 6 days/week, every day. | 12 month | | Typical quantity of alcohol consumption | Quantity of alcohol consumption within past 12 months measured as number of standard drinks (an Australian standard drink contains 10g alcohol). | 12 month | | Frequency of binge drinking | Frequency of drinking more than 4 standard drinks in the past 12 months | 12 month | | Experience of alcohol related harms | 17 item scale of alcohol related harms, adapted from the School Health and Alcohol Harm Reduction Project. Scores range from 0 to 85, with higher scores indicating greater experience of harms. | 12 months | | Symptoms of alcohol abuse, dependence and alcohol use disorder | Symptoms of alcohol abuse, dependence, and alcohol use disorder measured via the Diagnostic Interview Schedule for Children 4th Edition. Items correspond to Diagnostic and Statistical Manual of Mental Disorders 4th Edition symptoms of alcohol abuse (4 symptoms), dependence (7 symptoms), and alcohol use disorder (11 symptoms). | 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- adolescent, alcohol, parent, epidemiology

NCT04832399

Study of Tysabri in Early Relapsing Remitting Multiple Sclerosis Participants

The purpose of this study is to evaluate the impact of an early treatment with Natalizumab on the management of the progressive nature of Relapsing Remitting Multiple Sclerosis (RRMS).

Tysabri in Early Relapsing Remitting Multiple Sclerosis Patients - TYPIFI (Tysabri Patient Initiation After Failure of the Initial DMT)

Relapsing Remitting Multiple Sclerosis

* Drug: Natalizumab

Key Inclusion Criteria:~Documented diagnosis of Relapsing Remitting Multiple Sclerosis (McDonald 2010 Criteria).~EDSS ≤ 3.0.~Must fulfill Tysabri indication (relapse and MRI criteria).~Decision to start treatment with Natalizumab must precede enrollment.~Up to four natalizumab infusions.~Key Exclusion Criteria:~Any prior treatment with Natalizumab.~Prior imunossupressive treatment (Mitoxantrone, Azathioprine, Methotrexate, Cyclophosphamide, Mycophenolate, Cladribine, Rituximab).~Contraindications to treatment with Natalizumab.~History of Progressive Multifocal Leukoencephalopathy (PML) or other opportunistic infections, or an increased risk for such infections.~Immunocompromised at the time of enrollment. Known active malignancies.~Inability to comply with study requirements.~Note: Other protocol defined Inclusion/Exclusion criteria may apply.

18 Years

55 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall Disease-Free Status at Month 12 | | Month 12 | | Clinical Disease-Free Status at Month 12 in Comparison to the Previous Year | | Month 12 | | Annualized Relapse Rate at Month 12 in Comparison to the Previous Year | | Month 12 |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall Disease-Free Status at Months 24, 36 and 48 | | Months 24, 36 and 48 | | Clinical Disease-free Status Every 6 Months | | Every 6 months (Up to 48 months) | | Annualized Relapse Rate (ARR) | | Months 12, 24, 36 and 48 | | Change From Baseline in Sustained Expanded Disability Status Scale (EDSS) Score (24-week Sustained) | The EDSS is used to quantify disability due to symptoms of MS and to track changes in disability status over time. Scores range from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). | Months 12, 24, 36 and 48 | | MRI measures: T2, T1, T1 with Gadolinium (Gd) | | Months 12, 24, 36 and 48 | | Cognitive Impairment Using Symbol Digit Modalities Test (SDMT) | | Months 12, 24, 36 and 48 | | Change From Baseline in Ability to Work and Productivity as Assessed by Work Productivity and Activity Impairment (WPAI) Questionnaire | The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. WPAI outcomes are expressed as impairment percentages ranging from 0-100%, with higher numbers indicating greater impairment and less productivity. | Months 12, 24, 36 and 48 | | Quality of life (QoL) Assessed Using Fatigue Severity Scale | The FSS is a self-assessment questionnaire that provides a score as a measurement of the severity of fatigue. It consists of 9 questions scored from 1 to 7. A low value (e.g., 1); indicates strong disagreement with the statement, whereas a high value (e.g., 7); indicates strong agreement. A total score of 36 or more suggests presence of fatigue. | Months 12, 24, 36 and 48 | | QoL assessed using Multiple Sclerosis Functional Composite (MSFC) Test | MSFC has 2 component- timed 25-foot walk (T25FW) and 9-hole peg test (9HPT) [dominant and nondominant hands]. The MSFC Z-score is calculated by creating Z-scores for each component of the MSFC and averaging them to create an overall composite score. MSFC Z-score = (Z25-foot-walk + Z9HPT-2)/2, where Zj refers to Z-scores of component j. A Z-score represented the number of standard deviations participant's test result was higher (Z >0) or lower (Z <0) than the average test result (Z = 0) from the reference population. Higher scores indicate better outcomes. | Months 12, 24, 36 and 48 | | QoL Assessed Using Beck Depression Inventory, 2nd Edition (BDI-II) | BDI-II Scale is a 21-item self-reported questionnaire which measures the existence and severity of symptoms of depression. Each of the 21 items on BDI-II tool represents a depressive symptom. The symptoms are each scored on a 4-point Likert scale of 0 to 3 (0=symptom is absent; 3=symptom is severe). Scores for each symptom are added up to obtain the total scores for all 21 items. Total score ranges from 0-63; of which 0-8 is considered no depression, 0-13 is minimal depression, 14-19 is mild depression, 20-28 is moderate depression and 29-63 is severe depression. | Months 12, 24, 36 and 48 | | QoL Assessed Using Multiple Sclerosis Impact Scale (MSIS-29) | MSIS-29 is a brief self-administered instrument measuring physical (20 items) and psychological (9 items) impact of Multiple Sclerosis (MS). Each of the 29 items on MSIS-29 tool is a question that ask for participants views about the impact of MS on their day to day lives. Each item is scored on 1 to 5 (1=Not at all; 5=Extremely). | Months 12, 24, 36 and 48 |

Natalizumab, Immunologic Factors, Physiological Effects of Drugs

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Natalizumab<br>Natalizumab 300 mg is administered by intravenous infusion once every 4 weeks. | Drug: Natalizumab<br>* As described in the treatment arm.<br>* Other names: BG00002;|

Study of Tysabri in Early Relapsing Remitting Multiple Sclerosis Participants Study Overview ================= Brief Summary ----------------- The purpose of this study is to evaluate the impact of an early treatment with Natalizumab on the management of the progressive nature of Relapsing Remitting Multiple Sclerosis (RRMS). Official Title ----------------- Tysabri in Early Relapsing Remitting Multiple Sclerosis Patients - TYPIFI (Tysabri Patient Initiation After Failure of the Initial DMT) Conditions ----------------- Relapsing Remitting Multiple Sclerosis Intervention / Treatment ----------------- * Drug: Natalizumab Participation Criteria ================= Eligibility Criteria ----------------- Key Inclusion Criteria: Documented diagnosis of Relapsing Remitting Multiple Sclerosis (McDonald 2010 Criteria). EDSS ≤ 3.0. Must fulfill Tysabri indication (relapse and MRI criteria). Decision to start treatment with Natalizumab must precede enrollment. Up to four natalizumab infusions. Key Exclusion Criteria: Any prior treatment with Natalizumab. Prior imunossupressive treatment (Mitoxantrone, Azathioprine, Methotrexate, Cyclophosphamide, Mycophenolate, Cladribine, Rituximab). Contraindications to treatment with Natalizumab. History of Progressive Multifocal Leukoencephalopathy (PML) or other opportunistic infections, or an increased risk for such infections. Immunocompromised at the time of enrollment. Known active malignancies. Inability to comply with study requirements. Note: Other protocol defined Inclusion/Exclusion criteria may apply. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 55 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Natalizumab<br>Natalizumab 300 mg is administered by intravenous infusion once every 4 weeks. | Drug: Natalizumab<br>* As described in the treatment arm.<br>* Other names: BG00002;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall Disease-Free Status at Month 12 | | Month 12 | | Clinical Disease-Free Status at Month 12 in Comparison to the Previous Year | | Month 12 | | Annualized Relapse Rate at Month 12 in Comparison to the Previous Year | | Month 12 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall Disease-Free Status at Months 24, 36 and 48 | | Months 24, 36 and 48 | | Clinical Disease-free Status Every 6 Months | | Every 6 months (Up to 48 months) | | Annualized Relapse Rate (ARR) | | Months 12, 24, 36 and 48 | | Change From Baseline in Sustained Expanded Disability Status Scale (EDSS) Score (24-week Sustained) | The EDSS is used to quantify disability due to symptoms of MS and to track changes in disability status over time. Scores range from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). | Months 12, 24, 36 and 48 | | MRI measures: T2, T1, T1 with Gadolinium (Gd) | | Months 12, 24, 36 and 48 | | Cognitive Impairment Using Symbol Digit Modalities Test (SDMT) | | Months 12, 24, 36 and 48 | | Change From Baseline in Ability to Work and Productivity as Assessed by Work Productivity and Activity Impairment (WPAI) Questionnaire | The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. WPAI outcomes are expressed as impairment percentages ranging from 0-100%, with higher numbers indicating greater impairment and less productivity. | Months 12, 24, 36 and 48 | | Quality of life (QoL) Assessed Using Fatigue Severity Scale | The FSS is a self-assessment questionnaire that provides a score as a measurement of the severity of fatigue. It consists of 9 questions scored from 1 to 7. A low value (e.g., 1); indicates strong disagreement with the statement, whereas a high value (e.g., 7); indicates strong agreement. A total score of 36 or more suggests presence of fatigue. | Months 12, 24, 36 and 48 | | QoL assessed using Multiple Sclerosis Functional Composite (MSFC) Test | MSFC has 2 component- timed 25-foot walk (T25FW) and 9-hole peg test (9HPT) [dominant and nondominant hands]. The MSFC Z-score is calculated by creating Z-scores for each component of the MSFC and averaging them to create an overall composite score. MSFC Z-score = (Z25-foot-walk + Z9HPT-2)/2, where Zj refers to Z-scores of component j. A Z-score represented the number of standard deviations participant's test result was higher (Z >0) or lower (Z <0) than the average test result (Z = 0) from the reference population. Higher scores indicate better outcomes. | Months 12, 24, 36 and 48 | | QoL Assessed Using Beck Depression Inventory, 2nd Edition (BDI-II) | BDI-II Scale is a 21-item self-reported questionnaire which measures the existence and severity of symptoms of depression. Each of the 21 items on BDI-II tool represents a depressive symptom. The symptoms are each scored on a 4-point Likert scale of 0 to 3 (0=symptom is absent; 3=symptom is severe). Scores for each symptom are added up to obtain the total scores for all 21 items. Total score ranges from 0-63; of which 0-8 is considered no depression, 0-13 is minimal depression, 14-19 is mild depression, 20-28 is moderate depression and 29-63 is severe depression. | Months 12, 24, 36 and 48 | | QoL Assessed Using Multiple Sclerosis Impact Scale (MSIS-29) | MSIS-29 is a brief self-administered instrument measuring physical (20 items) and psychological (9 items) impact of Multiple Sclerosis (MS). Each of the 29 items on MSIS-29 tool is a question that ask for participants views about the impact of MS on their day to day lives. Each item is scored on 1 to 5 (1=Not at all; 5=Extremely). | Months 12, 24, 36 and 48 |

NCT02861781

Collection of Human Metabolic Tissues

This project aims at identifying new determinants of type 2 diabetes in severe obesity. To do so, a biological collection, including tissues of interest in the field of metabolism, will be collected during bariatric surgery in obese patients. Three different groups of metabolic status of patients, corresponding to different stages of evolution of the disease, will be constituted: type 2 diabetes, insulin resistance, insulin sensitivity.~The main objective is to compare, between these 3 groups of patients, several biological processes that may be involved in the pathophysiology of type 2 diabetes and disorders associated with obesity, including:~Abnormalities of the transcriptome, proteome, metabolome in all target tissues (plasma, serum, muscle, subcutaneous and visceral adipose tissue, omental artery, liver)~Identification of metabolic signatures, protein and miRNA in plasma~Immunoinflammatory response in adipose tissue~Polymorphisms SNP from whole blood~Histological analysis of tissue sections This main objective will be studied on samples taken at the time of surgery Secondary objectives will be to study the changes in metabolites, proteins and miRNA in plasma level 3 and 12 months after the completion of surgery, according to the initial metabolic state.

Study of New Determinants of Type 2 Diabetes in Severe Obesity

Obesity, Insulin Resistance, Diabetes Mellitus, Type 2

* Other: Collection of blood samples and tissues

Inclusion Criteria:~Written informed consent~Age 18 - 65 years inclusive at surgery~IMC > 35~Subject qualified for bariatric surgery (sleeve gastrectomy or gastric bypass)~Specific criteria :~Type 2 diabetes group (D) (90 patients) : type 2 diabetes according to ADA criteria~Insulin resistance non diabetes group (IR) (80 patients) : HOMA-IR criteria ≥ 3~Insulin Sensitivity non diabetes group (N) (100 patients) : N1.HOMA-IR criteria < 3~Non inclusion Criteria:~Vulnerability according to article L1121-6 of the Public Health Code~Protected adult or unability to give consent according to article L1121-8 of the Public Health Code~Unability to understand the design and aims of the study or to communicate with the investigator~Non affiliation to a social security system~Prior bariatric surgery (except lap-band procedure)~Serologic profile indicating hepatitis B, hepatitis C or HIV infection~Inflammatory, infectious or autoimmune disease (current or in the previous 3 month)~Malignancies within 5 years prior to inclusion or not considered as treated curatively~Concomitant use of steroids or NSAI or use in the 8 days before surgery~alcohol abuse/addiction~Anticipated poor compliance to study procedures~Other type of diabetes than type 2~Exclusion Criteria :~Cancelled bariatric surgery~Tissue collection not possible during the bariatric surgery

18 Years

65 Years

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | comparison of metabolites | | At baseline (day of surgery) | | comparison of proteins levels | in liver, muscle, adipose tissue and plasma according to metabolic state | At baseline (day of surgery) | | comparison of miRNA | in liver, muscle, adipose tissue and plasma according to metabolic state | At baseline (day of surgery) |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | changes in metabolites in plasma level | | 3 and 12 months after the completion of surgery | | changes in proteins in plasma level | | 3 and 12 months after the completion of surgery | | changes in miRNA in plasma level | | 3 and 12 months after the completion of surgery |

Bariatric surgery

Obesity, Diabetes Mellitus, Type 2, Insulin Resistance, Overweight, Overnutrition, Nutrition Disorders, Body Weight, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Hyperinsulinism

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Type 2 diabetes<br>Type 2 diabetes according to ADA criteria | Other: Collection of blood samples and tissues<br>* Collection of blood samples and tissues during bariatric surgery and blood samples during followup visits<br>| | Insulin resistance non diabetes<br>HOMA-IR criteria ≥ 3 | Other: Collection of blood samples and tissues<br>* Collection of blood samples and tissues during bariatric surgery and blood samples during followup visits<br>| | Insulin sensitivity non diabetes<br>HOMA-IR criteria < 3 | Other: Collection of blood samples and tissues<br>* Collection of blood samples and tissues during bariatric surgery and blood samples during followup visits<br>|

Collection of Human Metabolic Tissues Study Overview ================= Brief Summary ----------------- This project aims at identifying new determinants of type 2 diabetes in severe obesity. To do so, a biological collection, including tissues of interest in the field of metabolism, will be collected during bariatric surgery in obese patients. Three different groups of metabolic status of patients, corresponding to different stages of evolution of the disease, will be constituted: type 2 diabetes, insulin resistance, insulin sensitivity. The main objective is to compare, between these 3 groups of patients, several biological processes that may be involved in the pathophysiology of type 2 diabetes and disorders associated with obesity, including: Abnormalities of the transcriptome, proteome, metabolome in all target tissues (plasma, serum, muscle, subcutaneous and visceral adipose tissue, omental artery, liver) Identification of metabolic signatures, protein and miRNA in plasma Immunoinflammatory response in adipose tissue Polymorphisms SNP from whole blood Histological analysis of tissue sections This main objective will be studied on samples taken at the time of surgery Secondary objectives will be to study the changes in metabolites, proteins and miRNA in plasma level 3 and 12 months after the completion of surgery, according to the initial metabolic state. Official Title ----------------- Study of New Determinants of Type 2 Diabetes in Severe Obesity Conditions ----------------- Obesity, Insulin Resistance, Diabetes Mellitus, Type 2 Intervention / Treatment ----------------- * Other: Collection of blood samples and tissues Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Written informed consent Age 18 - 65 years inclusive at surgery IMC > 35 Subject qualified for bariatric surgery (sleeve gastrectomy or gastric bypass) Specific criteria : Type 2 diabetes group (D) (90 patients) : type 2 diabetes according to ADA criteria Insulin resistance non diabetes group (IR) (80 patients) : HOMA-IR criteria ≥ 3 Insulin Sensitivity non diabetes group (N) (100 patients) : N1.HOMA-IR criteria < 3 Non inclusion Criteria: Vulnerability according to article L1121-6 of the Public Health Code Protected adult or unability to give consent according to article L1121-8 of the Public Health Code Unability to understand the design and aims of the study or to communicate with the investigator Non affiliation to a social security system Prior bariatric surgery (except lap-band procedure) Serologic profile indicating hepatitis B, hepatitis C or HIV infection Inflammatory, infectious or autoimmune disease (current or in the previous 3 month) Malignancies within 5 years prior to inclusion or not considered as treated curatively Concomitant use of steroids or NSAI or use in the 8 days before surgery alcohol abuse/addiction Anticipated poor compliance to study procedures Other type of diabetes than type 2 Exclusion Criteria : Cancelled bariatric surgery Tissue collection not possible during the bariatric surgery Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Type 2 diabetes<br>Type 2 diabetes according to ADA criteria | Other: Collection of blood samples and tissues<br>* Collection of blood samples and tissues during bariatric surgery and blood samples during followup visits<br>| | Insulin resistance non diabetes<br>HOMA-IR criteria ≥ 3 | Other: Collection of blood samples and tissues<br>* Collection of blood samples and tissues during bariatric surgery and blood samples during followup visits<br>| | Insulin sensitivity non diabetes<br>HOMA-IR criteria < 3 | Other: Collection of blood samples and tissues<br>* Collection of blood samples and tissues during bariatric surgery and blood samples during followup visits<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | comparison of metabolites | | At baseline (day of surgery) | | comparison of proteins levels | in liver, muscle, adipose tissue and plasma according to metabolic state | At baseline (day of surgery) | | comparison of miRNA | in liver, muscle, adipose tissue and plasma according to metabolic state | At baseline (day of surgery) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | changes in metabolites in plasma level | | 3 and 12 months after the completion of surgery | | changes in proteins in plasma level | | 3 and 12 months after the completion of surgery | | changes in miRNA in plasma level | | 3 and 12 months after the completion of surgery | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Bariatric surgery

NCT01581229

Early Use of Noninvasive Positive Pressure Ventilation for Intro-pulmonary Acute Lung Injury

To assess the safety and efficacy of noninvasive positive pressure ventilation for patients with intro-pulmonary pulmonary acute lung injury and compare this with high-concentration oxygen therapy.

Acute Lung Injury

* Procedure: noninvasive positive pressure ventilation * Procedure: oxygen therapy

Inclusion Criteria:~acute onset;~a clinical presentation of respiratory distress;~arterial oxygen tension/inspired oxygen fraction (PaO2/FIO2) < 300 mmHg but > 200 mmHg while breathing oxygen delivered by a conventional Venturi device at a maximum concentration (50%);~presence of bilateral pulmonary infiltrates on posteroanterior chest radiograph;~no evidence of left heart failure as assessed by echocardiography and/or a pulmonary artery wedge pressure of <18 mm Hg.~the cause of ALI is consider to be intro-pulmonary.~Exclusion Criteria:~age <18 yrs;~Glasgow Coma Scale < 11;~airway or facial injury;~pneumothorax or pneumomediastinum;~unable to spontaneously clear secretions from the airways;~cardiogenic shock or severe hemodynamic instability (systolic blood pressure <90 mmHg associated with decreased urinary output (<20 mL.h-1) despite fluid repletion and use of vasoactive agents) of other causes;~severe ventricular arrhythmia or unstable myocardial ischemia;~severe organ dysfunction (Sequential Organ Failure Assessment score > 3);~end-stage patients who were expected to survive < 6 months;~severe abdominal distension;~refusal to receive NPPV;~the cause of ALI is consider to be extrapulmonary;~unable to cooperate with NPPV application;~active upper gastrointestinal bleeding.

18 Years

All

No

Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | numbers of patients who met the intubation criteria | | 1 year | | the numbers of patients who are actually intubated | | 1 year |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | inhospital mortalities | | 1 year | | intensive care unit mortalities | | 1 year |

ALI;noninvasive positive pressure ventilation

Lung Injury, Acute Lung Injury, Wounds and Injuries, Lung Diseases, Respiratory Tract Diseases, Thoracic Injuries

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: NPPV<br> | Procedure: noninvasive positive pressure ventilation<br>* Patients in the NPPV group are ventilated using the CPAP or bilevel positive airways pressure S/T mode.<br>| | Active Comparator: Control<br> | Procedure: oxygen therapy<br>* In the control group, Venturi masks are used to maintain SpO2 at 92% to 96% by adjusting the oxygen flow rates.<br>|

Early Use of Noninvasive Positive Pressure Ventilation for Intro-pulmonary Acute Lung Injury Study Overview ================= Brief Summary ----------------- To assess the safety and efficacy of noninvasive positive pressure ventilation for patients with intro-pulmonary pulmonary acute lung injury and compare this with high-concentration oxygen therapy. Conditions ----------------- Acute Lung Injury Intervention / Treatment ----------------- * Procedure: noninvasive positive pressure ventilation * Procedure: oxygen therapy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: acute onset; a clinical presentation of respiratory distress; arterial oxygen tension/inspired oxygen fraction (PaO2/FIO2) < 300 mmHg but > 200 mmHg while breathing oxygen delivered by a conventional Venturi device at a maximum concentration (50%); presence of bilateral pulmonary infiltrates on posteroanterior chest radiograph; no evidence of left heart failure as assessed by echocardiography and/or a pulmonary artery wedge pressure of <18 mm Hg. the cause of ALI is consider to be intro-pulmonary. Exclusion Criteria: age <18 yrs; Glasgow Coma Scale < 11; airway or facial injury; pneumothorax or pneumomediastinum; unable to spontaneously clear secretions from the airways; cardiogenic shock or severe hemodynamic instability (systolic blood pressure <90 mmHg associated with decreased urinary output (<20 mL.h-1) despite fluid repletion and use of vasoactive agents) of other causes; severe ventricular arrhythmia or unstable myocardial ischemia; severe organ dysfunction (Sequential Organ Failure Assessment score > 3); end-stage patients who were expected to survive < 6 months; severe abdominal distension; refusal to receive NPPV; the cause of ALI is consider to be extrapulmonary; unable to cooperate with NPPV application; active upper gastrointestinal bleeding. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: NPPV<br> | Procedure: noninvasive positive pressure ventilation<br>* Patients in the NPPV group are ventilated using the CPAP or bilevel positive airways pressure S/T mode.<br>| | Active Comparator: Control<br> | Procedure: oxygen therapy<br>* In the control group, Venturi masks are used to maintain SpO2 at 92% to 96% by adjusting the oxygen flow rates.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | numbers of patients who met the intubation criteria | | 1 year | | the numbers of patients who are actually intubated | | 1 year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | inhospital mortalities | | 1 year | | intensive care unit mortalities | | 1 year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- ALI;noninvasive positive pressure ventilation

NCT05290818

Total Versus Robotic Assisted Unicompartmental Knee Replacement

The purpose of this research is to compare the functional outcomes of patients with end stage medial compartment OA of the knee undergoing a conventional mTKA to those undergoing rUKA and to assess the associated cost economics of such technology.

Unicompartmental knee arthroplasty (UKA) is an accepted surgical alternative to total knee arthroplasty (TKA) for patients with isolated medial compartmental joint disease with the potential advantages of accelerated recovery, improved functional outcomes and retention of anatomical knee kinematics. However, some surgeons continue to favour TKA over UKA due to a lower revision rate. The higher revision rates associated with UKA are thought to be primarily due to component malpositioning and postoperative limb malalignment.~Robotic-arm assisted (r)UKA offers a greater level of precision of component positioning compared to manual UKA and more recently the survivorship of rUKA has been shown to be greater than manual UKA. Early functional outcomes following robotic UKA appear to be better than those observed after manual TKA. Therefore, the benefits of UKA could potentially be enjoyed by the patient without the increased risk of revision when compared to TKA for those with medical compartment disease.~The primary aim of this study is to compare the early knee specific functional outcome of rUKA with manually performed (m)TKA when performed for patients with medial compartment osteoarthritis of the knee.~A single centre randomised control trial will be carried out powered to the Oxford knee score.

Total Versus Robotic Assisted Unicompartmental Knee Replacement (TRAKER) for Medial Compartment Osteoarthritis: Randomised Controlled Trial

Osteo Arthritis Knee, Arthritis Knee, Arthropathy of Knee

* Device: MAKO™ Partial Knee Arthroplasty * Device: Triathlon (Stryker) Total Knee Arthroplasty

Inclusion Criteria:~Listed for elective primary TKA for end stage medial compartment osteoarthritis~Intact anterior cruciate ligament~Full thickness and good quality lateral cartilage~Correctable intra-articular varus deformity and intact medial collateral ligament~American Society of Anesthesiologists (ASA) grades 1 and 2~Male or female, age 50 - 75 at the time of listing for surgery~Suitable candidate for a cruciate retaining TKA (Triathlon prosthesis) and a UKA~Exclusion Criteria:~Varus deformity of > 20 degrees~Fixed flexion of >10 degrees~Patient is unable to comply with the study protocol (incl. refusal for CT scan) or functional assessments~Female participants who are pregnant, lactating or planning pregnancy during the course of the study~Requires patella resurfacing or lateral compartment has significant OA~Inability to understand the patient information for the study, provide written informed consent or answer study questionnaires for cognitive or language reasons~Inflammatory disorder e.g. rheumatoid arthritis~Symptomatic foot, hip or spine pathology~Prior surgery (other than arthroscopy) or septic arthritis of the knee~Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study,

50 Years

75 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Randomised control Trial (1:2 ratio: 53 in the rUKA arm and 106 in the mTKA) Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Oxford knee score | Knee specific functional outcome measure. It consists of twelve questions assessed on a Likert scale with values from 0 to 4, to give a summative score. This is measured on a scale from 0 (worst) to 48 (best). | Baseline to 6 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Oxford knee score and Activity and Participation Questionnaire | The Oxford knee score is a knee specific functional outcome measure. It consists of twelve questions assessed on a Likert scale with values from 0 to 4, to give a summative score. This is measured on a scale from 0 (worst) to 48 (best). The additional Activity and Participation Questionnaire is a higher functioning supplementary questionnaire consisting of a further eight questions scored 0 (worst) to 4 (best). | Baseline to 3, 6 and 12 months | | Forgotten Joint Score | Knee specific functional outcome. It uses a five-point Likert response format, consisting of 12 equally weighted questions with the raw score transformed to range from zero (worst) to 100 (best) points. | Baseline to 3, 6 and 12 months | | Patient satisfaction | Patient satisfaction will be assessed following surgery by asking four questions with a different focus:~i. Overall how satisfied are you with the results of your knee replacement surgery? ii. How satisfied are you with the results of your knee replacement surgery for improving your ability to do housework or yard work (such as cooking, cleaning, or gardening and raking leaves)? iii. How satisfied are you with the results of your knee replacement surgery for improving your ability to do recreational activities (such as taking walks, swimming, bicycling, playing golf, dancing, going out with friends)? iv. How satisfied are you with the results of your knee replacement surgery for relieving your pain? The response to each question will be recorded using a four point Likert scale: very satisfied, somewhat satisfied, somewhat dissatisfied, and very dissatisfied. | 3, 6 and 12 months | | EQ-5D-3L | Quality of life will be assessed using the EQ-5D-3L general health questionnaire which evaluates five domains (-5D), which include: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. This is a two page questionnaire that consists of five dimensions, with the responses recorded at three levels (3L) of severity (no problems; some problems or extreme problems). The utility index is on a scale of -0.594 to 1, where 1 represents perfect health and a negative value represents a state perceived as worse than death.~The second page consists of a standard vertical 20cm visual analogue scale (EQ-5D VAS) which is transformed to a scale of 0 (worst) to 100 (best) measuring current health-related quality of life. Each patient's health state, derived from the EQ-5D, will be measured before and after their surgery to determine the change in their health gain or loss after their knee replacement surgery. | Baseline to 3, 6 and 12 months | | Range of movement | A goniometer will be used to measure range of movement by a blinded researcher prior to surgery (baseline), at discharge (immediately post surgery prior to discharge home) and at review appoints. Three measurements will be recorded for extension and flexion of the knee and an average will be documented. | Baseline to 3, 6 and 12 months | | Cost effectiveness | Cost utility analysis will be undertaken to establish the incremental cost effectiveness ratio (ICER). Each patient's health state, derived from the EQ-5D, will be measured before and after their surgery to determine the change in their health gain or loss after their knee replacement surgery. The health state will then be multiplied by the time spent in that state to derive the QALYs gained or lost. The cost per QALY will then be calculated by dividing the cost of the procedure by the QALYs gained after total knee arthroplasty (intervention). A health service resource use questionnaire will be completed by the patient at the 3, 6 and 12 month research assessment. The questionnaire collects data on primary, secondary and community care and associated with the knee replacement over the previous months. Inpatient and surgical data will be collected on the case report forms (CRF's) and complications will be recorded at each visit. | Baseline to 3, 6 and 12 months, and projected for the patients lifetime | | Knee stability and power | Knee stability (stress testing) and power (power rig) will be measured. A stress will be applied to the knee and the joint space opening will be measured using an ultrasound probe which will be used as a marker of knee stability. The power of the knee joint will be assessed using a standardise power rig Specific assessment of the patient's power output will be evaluated by a Leg Extensor Power Rig (Nottingham, UK), well validated for use with this population group. | Baseline to 3, 6 and 12 months | | Patient expectation pre-operative and fulfilment | The Hospital of Special Surgery Expectation questionnaire is a validated measure of patient pre-operative expectations of surgery. The level of patient expectation is indicated on a 5 point Likert scale as 'very important', 'somewhat important', 'a little important', 'I do not expect this' or 'this does not apply to me'. After surgery patients will complete a similar expectation questionnaire, but are asked whether the same expectations had been fulfilled, which again is assessed on a 5 point Likert scale as: 'greatly', 'a lot', 'a little', 'I did not expect this' or 'this did not apply to me'. | Baseline to 3, 6 and 12 months |

Arthroplasty, Robotic, Knee, Total, Partial, Outcome, MAKO

Arthritis, Osteoarthritis, Osteoarthritis, Knee, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Manual Total Knee Arthroplasty<br>This group will receive a conventional manual Triathlon (Stryker) TKA with a cruciate retaining polyethylene insert. The surgeon will then make bone cuts using a manual jig and a hand held saw to prepare the bone surfaces for the implant. A measured resection technique will be employed with a three degree tibial slope. The surgeon will use a conventional jig alignment technique for intramedullary referencing for the femur and extra medullary referencing for the tibia. Once the implant is in position the knee is then balanced by the feel though a range of movement and soft tissue releases will be performed as required to balance the knee in flexion and extension. | Device: Triathlon (Stryker) Total Knee Arthroplasty<br>* Triathlon (Stryker) TKA with a cruciate retaining polyethylene insert.<br>* Other names: Total Knee Replacement;| | Experimental: Robotic Assisted Unicompartmental Knee Arthroplasty<br>This group will receive the cemented Restoris MCK (Mako, Stryker) with a highly crossed linked (X3) polyethylene insert through a less invasive to the knee joint. Instead of using a manual jig and a hand held burr will be used to prepare the bone surfaces for the implant, the MAKO robotic arm will be used by the surgeon to cut the bone at the required alignment. The information from the CT scan will be used to create a 3D model of the patient's bony anatomy and will used to plan the positioning of the implant. Once the trackers are in place registration of the knee joint surface is performed. The specified bone cuts are then performed using the robotic arm, aiming to gap balance the knee through a full range of movement. | Device: MAKO™ Partial Knee Arthroplasty<br>* The robotic-arm will be used to position a partial knee arthroplasty.<br>* Other names: Robotic-arm assisted partial knee arthroplasty;|

Total Versus Robotic Assisted Unicompartmental Knee Replacement Study Overview ================= Brief Summary ----------------- The purpose of this research is to compare the functional outcomes of patients with end stage medial compartment OA of the knee undergoing a conventional mTKA to those undergoing rUKA and to assess the associated cost economics of such technology. Detailed Description ----------------- Unicompartmental knee arthroplasty (UKA) is an accepted surgical alternative to total knee arthroplasty (TKA) for patients with isolated medial compartmental joint disease with the potential advantages of accelerated recovery, improved functional outcomes and retention of anatomical knee kinematics. However, some surgeons continue to favour TKA over UKA due to a lower revision rate. The higher revision rates associated with UKA are thought to be primarily due to component malpositioning and postoperative limb malalignment. Robotic-arm assisted (r)UKA offers a greater level of precision of component positioning compared to manual UKA and more recently the survivorship of rUKA has been shown to be greater than manual UKA. Early functional outcomes following robotic UKA appear to be better than those observed after manual TKA. Therefore, the benefits of UKA could potentially be enjoyed by the patient without the increased risk of revision when compared to TKA for those with medical compartment disease. The primary aim of this study is to compare the early knee specific functional outcome of rUKA with manually performed (m)TKA when performed for patients with medial compartment osteoarthritis of the knee. A single centre randomised control trial will be carried out powered to the Oxford knee score. Official Title ----------------- Total Versus Robotic Assisted Unicompartmental Knee Replacement (TRAKER) for Medial Compartment Osteoarthritis: Randomised Controlled Trial Conditions ----------------- Osteo Arthritis Knee, Arthritis Knee, Arthropathy of Knee Intervention / Treatment ----------------- * Device: MAKO™ Partial Knee Arthroplasty * Device: Triathlon (Stryker) Total Knee Arthroplasty Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Listed for elective primary TKA for end stage medial compartment osteoarthritis Intact anterior cruciate ligament Full thickness and good quality lateral cartilage Correctable intra-articular varus deformity and intact medial collateral ligament American Society of Anesthesiologists (ASA) grades 1 and 2 Male or female, age 50 - 75 at the time of listing for surgery Suitable candidate for a cruciate retaining TKA (Triathlon prosthesis) and a UKA Exclusion Criteria: Varus deformity of > 20 degrees Fixed flexion of >10 degrees Patient is unable to comply with the study protocol (incl. refusal for CT scan) or functional assessments Female participants who are pregnant, lactating or planning pregnancy during the course of the study Requires patella resurfacing or lateral compartment has significant OA Inability to understand the patient information for the study, provide written informed consent or answer study questionnaires for cognitive or language reasons Inflammatory disorder e.g. rheumatoid arthritis Symptomatic foot, hip or spine pathology Prior surgery (other than arthroscopy) or septic arthritis of the knee Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, Ages Eligible for Study ----------------- Minimum Age: 50 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Randomised control Trial (1:2 ratio: 53 in the rUKA arm and 106 in the mTKA) Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Manual Total Knee Arthroplasty<br>This group will receive a conventional manual Triathlon (Stryker) TKA with a cruciate retaining polyethylene insert. The surgeon will then make bone cuts using a manual jig and a hand held saw to prepare the bone surfaces for the implant. A measured resection technique will be employed with a three degree tibial slope. The surgeon will use a conventional jig alignment technique for intramedullary referencing for the femur and extra medullary referencing for the tibia. Once the implant is in position the knee is then balanced by the feel though a range of movement and soft tissue releases will be performed as required to balance the knee in flexion and extension. | Device: Triathlon (Stryker) Total Knee Arthroplasty<br>* Triathlon (Stryker) TKA with a cruciate retaining polyethylene insert.<br>* Other names: Total Knee Replacement;| | Experimental: Robotic Assisted Unicompartmental Knee Arthroplasty<br>This group will receive the cemented Restoris MCK (Mako, Stryker) with a highly crossed linked (X3) polyethylene insert through a less invasive to the knee joint. Instead of using a manual jig and a hand held burr will be used to prepare the bone surfaces for the implant, the MAKO robotic arm will be used by the surgeon to cut the bone at the required alignment. The information from the CT scan will be used to create a 3D model of the patient's bony anatomy and will used to plan the positioning of the implant. Once the trackers are in place registration of the knee joint surface is performed. The specified bone cuts are then performed using the robotic arm, aiming to gap balance the knee through a full range of movement. | Device: MAKO™ Partial Knee Arthroplasty<br>* The robotic-arm will be used to position a partial knee arthroplasty.<br>* Other names: Robotic-arm assisted partial knee arthroplasty;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Oxford knee score | Knee specific functional outcome measure. It consists of twelve questions assessed on a Likert scale with values from 0 to 4, to give a summative score. This is measured on a scale from 0 (worst) to 48 (best). | Baseline to 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Oxford knee score and Activity and Participation Questionnaire | The Oxford knee score is a knee specific functional outcome measure. It consists of twelve questions assessed on a Likert scale with values from 0 to 4, to give a summative score. This is measured on a scale from 0 (worst) to 48 (best). The additional Activity and Participation Questionnaire is a higher functioning supplementary questionnaire consisting of a further eight questions scored 0 (worst) to 4 (best). | Baseline to 3, 6 and 12 months | | Forgotten Joint Score | Knee specific functional outcome. It uses a five-point Likert response format, consisting of 12 equally weighted questions with the raw score transformed to range from zero (worst) to 100 (best) points. | Baseline to 3, 6 and 12 months | | Patient satisfaction | Patient satisfaction will be assessed following surgery by asking four questions with a different focus: i. Overall how satisfied are you with the results of your knee replacement surgery? ii. How satisfied are you with the results of your knee replacement surgery for improving your ability to do housework or yard work (such as cooking, cleaning, or gardening and raking leaves)? iii. How satisfied are you with the results of your knee replacement surgery for improving your ability to do recreational activities (such as taking walks, swimming, bicycling, playing golf, dancing, going out with friends)? iv. How satisfied are you with the results of your knee replacement surgery for relieving your pain? The response to each question will be recorded using a four point Likert scale: very satisfied, somewhat satisfied, somewhat dissatisfied, and very dissatisfied. | 3, 6 and 12 months | | EQ-5D-3L | Quality of life will be assessed using the EQ-5D-3L general health questionnaire which evaluates five domains (-5D), which include: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. This is a two page questionnaire that consists of five dimensions, with the responses recorded at three levels (3L) of severity (no problems; some problems or extreme problems). The utility index is on a scale of -0.594 to 1, where 1 represents perfect health and a negative value represents a state perceived as worse than death. The second page consists of a standard vertical 20cm visual analogue scale (EQ-5D VAS) which is transformed to a scale of 0 (worst) to 100 (best) measuring current health-related quality of life. Each patient's health state, derived from the EQ-5D, will be measured before and after their surgery to determine the change in their health gain or loss after their knee replacement surgery. | Baseline to 3, 6 and 12 months | | Range of movement | A goniometer will be used to measure range of movement by a blinded researcher prior to surgery (baseline), at discharge (immediately post surgery prior to discharge home) and at review appoints. Three measurements will be recorded for extension and flexion of the knee and an average will be documented. | Baseline to 3, 6 and 12 months | | Cost effectiveness | Cost utility analysis will be undertaken to establish the incremental cost effectiveness ratio (ICER). Each patient's health state, derived from the EQ-5D, will be measured before and after their surgery to determine the change in their health gain or loss after their knee replacement surgery. The health state will then be multiplied by the time spent in that state to derive the QALYs gained or lost. The cost per QALY will then be calculated by dividing the cost of the procedure by the QALYs gained after total knee arthroplasty (intervention). A health service resource use questionnaire will be completed by the patient at the 3, 6 and 12 month research assessment. The questionnaire collects data on primary, secondary and community care and associated with the knee replacement over the previous months. Inpatient and surgical data will be collected on the case report forms (CRF's) and complications will be recorded at each visit. | Baseline to 3, 6 and 12 months, and projected for the patients lifetime | | Knee stability and power | Knee stability (stress testing) and power (power rig) will be measured. A stress will be applied to the knee and the joint space opening will be measured using an ultrasound probe which will be used as a marker of knee stability. The power of the knee joint will be assessed using a standardise power rig Specific assessment of the patient's power output will be evaluated by a Leg Extensor Power Rig (Nottingham, UK), well validated for use with this population group. | Baseline to 3, 6 and 12 months | | Patient expectation pre-operative and fulfilment | The Hospital of Special Surgery Expectation questionnaire is a validated measure of patient pre-operative expectations of surgery. The level of patient expectation is indicated on a 5 point Likert scale as 'very important', 'somewhat important', 'a little important', 'I do not expect this' or 'this does not apply to me'. After surgery patients will complete a similar expectation questionnaire, but are asked whether the same expectations had been fulfilled, which again is assessed on a 5 point Likert scale as: 'greatly', 'a lot', 'a little', 'I did not expect this' or 'this did not apply to me'. | Baseline to 3, 6 and 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Arthroplasty, Robotic, Knee, Total, Partial, Outcome, MAKO

NCT03689647

Using the Arms to Drive the Legs During Walking

This study aims to understand and compare the metabolic and mechanical demands placed on the body while walking normally and walking with the use of an apparatus that drives leg swing through the use of the arms. This information will help the investigators identify how arm swing mechanics helps minimize energy demands and to use this knowledge to design walking rehabilitation interventions in the future.

Reducing Metabolic Cost of Walking by Exploiting Arm Swing to Drive Leg Swing

Metabolic Cost of Walking With Arm Swing Assistive Device

* Device: Arm Swing Driven Assistive Apparatus

Inclusion Criteria:~Apparently healthy and free from neurological disease and/or body related injury~Community-dwelling young men and women 18-36 yrs~Use and be contacted by telephone~Speak, read, understand, and complete a questionnaire in English~Body mass index < 30 kg/m2~Exclusion Criteria:~not of the specified age range or Body Mass Index~inadequate aerobic fitness training~answering no to question #3 on Screening Form (Is participant in good general health?)~answering yes to:~question #4 (any difficulty with mobility?)~question #5 (problems with balance/dizziness?)~question #6 (lingering symptoms/pain from injury?)~question #7 (chest pain/shortness of breath?)~question #8 (high blood pressure/hypertension?), or~questions #9, 10, 11 (first degree family history of heart attack?)~question #12 (smoke cigarettes?)~question #13 (diabetes?)~question #14 (high cholesterol?)~question #15 (Is participant pregnant?)

18 Years

36 Years

All

Accepts Healthy Volunteers

Primary Purpose: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Metabolic Cost | Change in Metabolic Cost | Change from walking without assistive apparatus to walking with assistive apparatus. Measures of metabolic cost are completed within a 3-hour time window during a single laboratory visit. |

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Single Group Experimental<br>Each participant will act as their own control with variables of interest measured while walking without the assistive device and while walking with the assistive device. | Device: Arm Swing Driven Assistive Apparatus<br>* The investigators are testing a simple, custom built apparatus to determine if it can facilitate the use of the arms to swing the legs during walking. More specifically, the investigators will measure how this assistive apparatus affects the metabolic cost and biomechanics of walking.<br>|

Using the Arms to Drive the Legs During Walking Study Overview ================= Brief Summary ----------------- This study aims to understand and compare the metabolic and mechanical demands placed on the body while walking normally and walking with the use of an apparatus that drives leg swing through the use of the arms. This information will help the investigators identify how arm swing mechanics helps minimize energy demands and to use this knowledge to design walking rehabilitation interventions in the future. Official Title ----------------- Reducing Metabolic Cost of Walking by Exploiting Arm Swing to Drive Leg Swing Conditions ----------------- Metabolic Cost of Walking With Arm Swing Assistive Device Intervention / Treatment ----------------- * Device: Arm Swing Driven Assistive Apparatus Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Apparently healthy and free from neurological disease and/or body related injury Community-dwelling young men and women 18-36 yrs Use and be contacted by telephone Speak, read, understand, and complete a questionnaire in English Body mass index < 30 kg/m2 Exclusion Criteria: not of the specified age range or Body Mass Index inadequate aerobic fitness training answering no to question #3 on Screening Form (Is participant in good general health?) answering yes to: question #4 (any difficulty with mobility?) question #5 (problems with balance/dizziness?) question #6 (lingering symptoms/pain from injury?) question #7 (chest pain/shortness of breath?) question #8 (high blood pressure/hypertension?), or questions #9, 10, 11 (first degree family history of heart attack?) question #12 (smoke cigarettes?) question #13 (diabetes?) question #14 (high cholesterol?) question #15 (Is participant pregnant?) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 36 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Single Group Experimental<br>Each participant will act as their own control with variables of interest measured while walking without the assistive device and while walking with the assistive device. | Device: Arm Swing Driven Assistive Apparatus<br>* The investigators are testing a simple, custom built apparatus to determine if it can facilitate the use of the arms to swing the legs during walking. More specifically, the investigators will measure how this assistive apparatus affects the metabolic cost and biomechanics of walking.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Metabolic Cost | Change in Metabolic Cost | Change from walking without assistive apparatus to walking with assistive apparatus. Measures of metabolic cost are completed within a 3-hour time window during a single laboratory visit. |

NCT00705562

Tolerance of Healthy Term Infants Fed Infant Formulas

The objective of the study is to assess comparative gastrointestinal tolerance of normal term infants to various milk-protein infant formulas.

Tolerance of Healthy Term Infants Fed Infant Formulas

Infant, Newborn

* Other: milk protein formulas, varying carbohydrate/protein sources

Inclusion Criteria:~Healthy, term infants; singleton birth; 37-42 weeks of age; >2490gms at birth; 0-8 days of age~Exclusion Criteria:~medications/foods/formulas affecting GI tolerance;adverse medical history with possible effect on tolerance or growth

8 Days

All

Accepts Healthy Volunteers

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Gastrointestinal tolerance | | 0-8 days of age until 28 days of age |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | GI and intake parameters | | 0-8 to 28 days of age |

Caseins, Chelating Agents, Sequestering Agents, Molecular Mechanisms of Pharmacological Action

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: 1<br>Experimental milk protein based infant formula with varying carbohydrate and protein source | Other: milk protein formulas, varying carbohydrate/protein sources<br>* ad lib for 0-8 days of age until 28 days of age<br>| | Experimental: 2<br>Experimental milk protein based infant formula with varying carbohydrate and protein source | Other: milk protein formulas, varying carbohydrate/protein sources<br>* ad lib for 0-8 days of age until 28 days of age<br>| | Experimental: 3<br>Experimental milk protein based infant formula with varying carbohydrate and protein source | Other: milk protein formulas, varying carbohydrate/protein sources<br>* ad lib for 0-8 days of age until 28 days of age<br>| | Experimental: 4<br>Experimental milk protein based infant formula with varying carbohydrate and protein source | Other: milk protein formulas, varying carbohydrate/protein sources<br>* ad lib for 0-8 days of age until 28 days of age<br>| | Experimental: 5<br>Experimental milk protein based infant formula with varying carbohydrate and protein source | Other: milk protein formulas, varying carbohydrate/protein sources<br>* ad lib for 0-8 days of age until 28 days of age<br>|

Tolerance of Healthy Term Infants Fed Infant Formulas Study Overview ================= Brief Summary ----------------- The objective of the study is to assess comparative gastrointestinal tolerance of normal term infants to various milk-protein infant formulas. Official Title ----------------- Tolerance of Healthy Term Infants Fed Infant Formulas Conditions ----------------- Infant, Newborn Intervention / Treatment ----------------- * Other: milk protein formulas, varying carbohydrate/protein sources Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Healthy, term infants; singleton birth; 37-42 weeks of age; >2490gms at birth; 0-8 days of age Exclusion Criteria: medications/foods/formulas affecting GI tolerance;adverse medical history with possible effect on tolerance or growth Ages Eligible for Study ----------------- Maximum Age: 8 Days Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: 1<br>Experimental milk protein based infant formula with varying carbohydrate and protein source | Other: milk protein formulas, varying carbohydrate/protein sources<br>* ad lib for 0-8 days of age until 28 days of age<br>| | Experimental: 2<br>Experimental milk protein based infant formula with varying carbohydrate and protein source | Other: milk protein formulas, varying carbohydrate/protein sources<br>* ad lib for 0-8 days of age until 28 days of age<br>| | Experimental: 3<br>Experimental milk protein based infant formula with varying carbohydrate and protein source | Other: milk protein formulas, varying carbohydrate/protein sources<br>* ad lib for 0-8 days of age until 28 days of age<br>| | Experimental: 4<br>Experimental milk protein based infant formula with varying carbohydrate and protein source | Other: milk protein formulas, varying carbohydrate/protein sources<br>* ad lib for 0-8 days of age until 28 days of age<br>| | Experimental: 5<br>Experimental milk protein based infant formula with varying carbohydrate and protein source | Other: milk protein formulas, varying carbohydrate/protein sources<br>* ad lib for 0-8 days of age until 28 days of age<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Gastrointestinal tolerance | | 0-8 days of age until 28 days of age | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | GI and intake parameters | | 0-8 to 28 days of age |

NCT04929509

P11-4 and Nanosilver Fluoride Varnish in Treatment of White Spot Carious Lesions

Background: Great efforts have been undertaken for dental caries prevention. Among the recent remineralizing materials, Nano silver fluoride varnish products which are based on nanotechnology have been proposed for repairing enamel . Regenerative medicine-based approaches for caries treatment focus on biomimetic remineralization of initial carious lesions as a minimal invasive therapy using Self-Assembling Peptide P11-4 (Curodont Repair) which enhances remineralization of white spot lesions. Purpose of the Study: The aim of this study is to compare clinically and microbiologically the therapeutic effect of Self Assembling Peptide P11-4 (Curodont Repair), nano silver fluoride varnish and 5% fluoride varnish (Duraflor) on remineralization of enamel White Spot Lesions in permanent teeth of adults.

The study will be a randomized controlled double-blinded study conducted on participants aged 10 to 24 years satisfying the inclusion criteria with visible active white spot lesions on buccal surfaces of permanent teeth. Sixty six patients will be randomly allocated into 3 groups of the three materials: study group 1: one application of Curodont Repair, study group 2: one application of Nano-silver fluoride varnish and Control group twice application of Fluoride Varnish (Duraflor).

Effectiveness of Self-assembling Peptide (P11-4) and Nano-silver Fluoride Varnish in Management of Enamel White Spot Lesions in Young People (Randomized Controlled Clinical Trial)

White Spot Lesion

* Other: self-assembling peptide * Other: nanosilver fluoride varnish * Other: sodium fluoride varnish

Inclusion Criteria:~1- An age range of 10-24 years ( age of young adolescents and youth as described by the WHO was selected (WHO, 2019). 2. The presence of at least one visible WSL in the buccal surface of permanent teeth with ICDAS II score of 1, or 2. 3. Completion of an informed consent to participate in the study~Exclusion Criteria:~1. Patients receiving the following medications: tetracyclines, any other medication known to stain teeth or any medication causing dry mouth and/or limiting salivary flow. 2. Patients receiving any antibiotic within 1 month prior to each saliva sample collection 3. Selected tooth with microcavities or dentinal involvement due to loss of enamel tissues. 4. Selected tooth with a restoration adjacent to the lesions to avoid false- positive readings. 5. Selected tooth with fluoride application &lt; 3 months prior to study treatment. 6. Selected tooth with discolouration, enamel hypoplasia or fluorosis. 7. Patients with multiple cavitations to avoid variability in microbiological analysis.

10 Years

24 Years

All

Accepts Healthy Volunteers

Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in the activity status of lesions scored using ICDAS-LAA | Change in the activity status of lesions scored using ICDAS-LAA from baseline to final follow up. | 12 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in mean DIAGNOdent readings. | Change in mean DIAGNOdent readings from baseline to each follow up period | 12 months | | Microbial count of mutans streptococci, lactobacilli. | Microbial count of mutans streptococci, lactobacilli.from baseline to each follow up period | 6 months |

Fluorides, Sodium Fluoride, Fluorides, Topical, Cariostatic Agents, Protective Agents, Physiological Effects of Drugs, Anti-Infective Agents, Local, Anti-Infective Agents, Listerine

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: self-assembling peptide (P11-4)<br>Curodont Repair; Credentis will be applied to the~white spot lesion at baseline. | Other: self-assembling peptide<br>* each Curodont Repair applicator unit contains both Curolox technology for guided enamel regeneration and water for activation of the device, each box contains 10 applicators<br>* Other names: Curodont repair;| | Active Comparator: nanosilver fluoride varnish<br>(Study group) Nano-silver fluoride varnish will be applied to the~white spot lesion at baseline. | Other: nanosilver fluoride varnish<br>* The synthesis of aqueous solution of silver nanoparticles will be carried out via the chemical reduction of silver nitrate (1 mL, 0.11 M) with sodium borohydride (0.3 mL, 0.8 M) and chitosan biopolymer (28.7 mL, 2.5 mg/mL) as a stabilizing agent. Sodium fluoride (10,147 ppm of fluorine) will be incorporated at the end of the experiment.<br>| | Placebo Comparator: sodium fluoride varnish<br>(Control group) Fluoride varnish (Duraflor) will be applied to the~white spot lesion at baseline and 6 months follow up. | Other: sodium fluoride varnish<br>* 5% sodium fluoride varnish; One ml of fluoride varnish contains 50 mg of sodium fluoride in an alcohol-based suspension of resins.<br>* Other names: duraflor;|

P11-4 and Nanosilver Fluoride Varnish in Treatment of White Spot Carious Lesions Study Overview ================= Brief Summary ----------------- Background: Great efforts have been undertaken for dental caries prevention. Among the recent remineralizing materials, Nano silver fluoride varnish products which are based on nanotechnology have been proposed for repairing enamel . Regenerative medicine-based approaches for caries treatment focus on biomimetic remineralization of initial carious lesions as a minimal invasive therapy using Self-Assembling Peptide P11-4 (Curodont Repair) which enhances remineralization of white spot lesions. Purpose of the Study: The aim of this study is to compare clinically and microbiologically the therapeutic effect of Self Assembling Peptide P11-4 (Curodont Repair), nano silver fluoride varnish and 5% fluoride varnish (Duraflor) on remineralization of enamel White Spot Lesions in permanent teeth of adults. Detailed Description ----------------- The study will be a randomized controlled double-blinded study conducted on participants aged 10 to 24 years satisfying the inclusion criteria with visible active white spot lesions on buccal surfaces of permanent teeth. Sixty six patients will be randomly allocated into 3 groups of the three materials: study group 1: one application of Curodont Repair, study group 2: one application of Nano-silver fluoride varnish and Control group twice application of Fluoride Varnish (Duraflor). Official Title ----------------- Effectiveness of Self-assembling Peptide (P11-4) and Nano-silver Fluoride Varnish in Management of Enamel White Spot Lesions in Young People (Randomized Controlled Clinical Trial) Conditions ----------------- White Spot Lesion Intervention / Treatment ----------------- * Other: self-assembling peptide * Other: nanosilver fluoride varnish * Other: sodium fluoride varnish Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 1- An age range of 10-24 years ( age of young adolescents and youth as described by the WHO was selected (WHO, 2019). 2. The presence of at least one visible WSL in the buccal surface of permanent teeth with ICDAS II score of 1, or 2. 3. Completion of an informed consent to participate in the study Exclusion Criteria: 1. Patients receiving the following medications: tetracyclines, any other medication known to stain teeth or any medication causing dry mouth and/or limiting salivary flow. 2. Patients receiving any antibiotic within 1 month prior to each saliva sample collection 3. Selected tooth with microcavities or dentinal involvement due to loss of enamel tissues. 4. Selected tooth with a restoration adjacent to the lesions to avoid false- positive readings. 5. Selected tooth with fluoride application &lt; 3 months prior to study treatment. 6. Selected tooth with discolouration, enamel hypoplasia or fluorosis. 7. Patients with multiple cavitations to avoid variability in microbiological analysis. Ages Eligible for Study ----------------- Minimum Age: 10 Years Maximum Age: 24 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: self-assembling peptide (P11-4)<br>Curodont Repair; Credentis will be applied to the white spot lesion at baseline. | Other: self-assembling peptide<br>* each Curodont Repair applicator unit contains both Curolox technology for guided enamel regeneration and water for activation of the device, each box contains 10 applicators<br>* Other names: Curodont repair;| | Active Comparator: nanosilver fluoride varnish<br>(Study group) Nano-silver fluoride varnish will be applied to the white spot lesion at baseline. | Other: nanosilver fluoride varnish<br>* The synthesis of aqueous solution of silver nanoparticles will be carried out via the chemical reduction of silver nitrate (1 mL, 0.11 M) with sodium borohydride (0.3 mL, 0.8 M) and chitosan biopolymer (28.7 mL, 2.5 mg/mL) as a stabilizing agent. Sodium fluoride (10,147 ppm of fluorine) will be incorporated at the end of the experiment.<br>| | Placebo Comparator: sodium fluoride varnish<br>(Control group) Fluoride varnish (Duraflor) will be applied to the white spot lesion at baseline and 6 months follow up. | Other: sodium fluoride varnish<br>* 5% sodium fluoride varnish; One ml of fluoride varnish contains 50 mg of sodium fluoride in an alcohol-based suspension of resins.<br>* Other names: duraflor;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in the activity status of lesions scored using ICDAS-LAA | Change in the activity status of lesions scored using ICDAS-LAA from baseline to final follow up. | 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in mean DIAGNOdent readings. | Change in mean DIAGNOdent readings from baseline to each follow up period | 12 months | | Microbial count of mutans streptococci, lactobacilli. | Microbial count of mutans streptococci, lactobacilli.from baseline to each follow up period | 6 months |

NCT02004860

Tacrolimus Ointment Interest (PROTOPIC ®) in the Maintenance Treatment of Severe Seborrheic Dermatitis

Seborrheic dermatitis is a chronic inflammatory dermatological disease, evolving by relapses, affecting mainly the face and scalp. It would be important to have a maintenance treatment for severe forms of seborrheic dermatitis witch is both effective and relatively well tolerated to reduce the frequency of relapses, prolong remissions obtained after attack treatment and reduce the use of topical steroids.

Phase 3 : Tacrolimus Ointment Interest (PROTOPIC ®) in the Maintenance Treatment of Severe Seborrheic Dermatitis on Adult Face

Severe Seborrheic Dermatitis

* Drug: Protopic (R) * Drug: Mycoster (R)

Inclusion Criteria:~in Phase 1: Attack Treatment (open)~over the age of eighteen patient,~Seborrheic dermatitis Severe,~participation with an informed consent,~Women of childbearing age in effective contraception for the duration of the study or postmenopausal women.~in Phase 2: Phase 2: Randomization (blind)~Patient achieved a complete or almost complete clinical remission after the initial treatment,~known immunodeficiency (HIV patient receiving chemotherapy) or immunosuppressive therapy or biotherapy,~patient taking regular systemic corticosteroids at a dose> 20 mg / day~erythematous lesions with topography other than the face and evocative scalp psoriasis (elbows, knees ...), by referring to the possibility that the facial lesions correspond to lesions sebopsoriasis,~woman pregnant, nursing or in childbearing potential without effective contraception,~man wishing to have a child during the study period,~Ultra Violet (UV) phototherapy or usual realization of UV sessions aesthetic purposes,~Seborrheic dermatitis symptomatic of an underlying disease known or revealing~history of cancer or lymphoma,~progressive cancer or lymphoma,~Seborrheic dermatitis exclusively affecting the scalp,~known allergy to one-component products study ,~malnourished patient or sick history of chronic pancreatitis by a suspect to deficiency dermatitis,~participation in a clinical trial on the Seborrheic dermatitis in the previous 90 days,~patient with lesions considered potentially malignant or pre-cancerous,~patient with abnormal skin barrier.~Exclusion Criteria:~in Phase 1: Attack Treatment (open)~1) Patient had already been treated with Protopic ® for Seborrheic Dermatitis,~Phase 2: Randomization (blind) 1) Patient with no complete or almost complete clinical remission after the initial treatment,

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | duration of the maintenance of complete or almost complete clinical remission | The primary endpoint will be the duration of the maintenance of complete or almost complete clinical remission obtained after the initial treatment. This period is defined as the time from randomization to the first occurrence of relapse noted by the dermatologist. | 18 months after inclusion (Visit (V) 4 last visit) |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Tolerance of 2 treatments | Tolerance of 2 treatments Mycoster (R) and Protocopic (R) | between 10 days and 18 months after inclusion (V3 (Day (D)10 to D180)), 30 days after inclusion (Visit D30), after 90 days after inclusion (D90) and after 120 days after inclusion (D120) and 180 days after inclusion (Visit V4) | | Number of Relapses | Number of Relapses requiring the resumption of topical corticosteroid treatment, | 180 days after inclusion (Visit V4) | | Cumulative amount of corticosteroids applied | Cumulative amount of corticosteroids applied by the patients during the study period to control their outbreaks | between 10 days and 18 months after inclusion (V3 (D10 to D180)), 30 days after inclusion (Visit D30), after 90 days after inclusion (D90) and after 120 days after inclusion (D120) and 180 days after inclusion (Visit V4) | | quality of life of patients | quality of life of patients | Inclusion (visit D0) and Last visit 180 days after inclusion (Visit D180) |

local immunosuppressive, Maintenance therapy

Ciclopirox, Tacrolimus, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs, Calcineurin Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antifungal Agents, Anti-Infective Agents

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Protopic Arm<br>Protopic® 0.1% ointment - 2 applications per week for 6 months | Drug: Protopic (R)<br>* Protopic® 0.1% ointment - 2 applications per week for 6 months<br>* Other names: Tacrolimus;| | Active Comparator: Mycoster Arm<br>2 applications per week for 6 months | Drug: Mycoster (R)<br>* Mycoster 1% - 2 applications per week for 6 months<br>* Other names: Ciclopirox olamine;|

Tacrolimus Ointment Interest (PROTOPIC ®) in the Maintenance Treatment of Severe Seborrheic Dermatitis Study Overview ================= Brief Summary ----------------- Seborrheic dermatitis is a chronic inflammatory dermatological disease, evolving by relapses, affecting mainly the face and scalp. It would be important to have a maintenance treatment for severe forms of seborrheic dermatitis witch is both effective and relatively well tolerated to reduce the frequency of relapses, prolong remissions obtained after attack treatment and reduce the use of topical steroids. Official Title ----------------- Phase 3 : Tacrolimus Ointment Interest (PROTOPIC ®) in the Maintenance Treatment of Severe Seborrheic Dermatitis on Adult Face Conditions ----------------- Severe Seborrheic Dermatitis Intervention / Treatment ----------------- * Drug: Protopic (R) * Drug: Mycoster (R) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: in Phase 1: Attack Treatment (open) over the age of eighteen patient, Seborrheic dermatitis Severe, participation with an informed consent, Women of childbearing age in effective contraception for the duration of the study or postmenopausal women. in Phase 2: Phase 2: Randomization (blind) Patient achieved a complete or almost complete clinical remission after the initial treatment, known immunodeficiency (HIV patient receiving chemotherapy) or immunosuppressive therapy or biotherapy, patient taking regular systemic corticosteroids at a dose> 20 mg / day erythematous lesions with topography other than the face and evocative scalp psoriasis (elbows, knees ...), by referring to the possibility that the facial lesions correspond to lesions sebopsoriasis, woman pregnant, nursing or in childbearing potential without effective contraception, man wishing to have a child during the study period, Ultra Violet (UV) phototherapy or usual realization of UV sessions aesthetic purposes, Seborrheic dermatitis symptomatic of an underlying disease known or revealing history of cancer or lymphoma, progressive cancer or lymphoma, Seborrheic dermatitis exclusively affecting the scalp, known allergy to one-component products study , malnourished patient or sick history of chronic pancreatitis by a suspect to deficiency dermatitis, participation in a clinical trial on the Seborrheic dermatitis in the previous 90 days, patient with lesions considered potentially malignant or pre-cancerous, patient with abnormal skin barrier. Exclusion Criteria: in Phase 1: Attack Treatment (open) 1) Patient had already been treated with Protopic ® for Seborrheic Dermatitis, Phase 2: Randomization (blind) 1) Patient with no complete or almost complete clinical remission after the initial treatment, Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Protopic Arm<br>Protopic® 0.1% ointment - 2 applications per week for 6 months | Drug: Protopic (R)<br>* Protopic® 0.1% ointment - 2 applications per week for 6 months<br>* Other names: Tacrolimus;| | Active Comparator: Mycoster Arm<br>2 applications per week for 6 months | Drug: Mycoster (R)<br>* Mycoster 1% - 2 applications per week for 6 months<br>* Other names: Ciclopirox olamine;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | duration of the maintenance of complete or almost complete clinical remission | The primary endpoint will be the duration of the maintenance of complete or almost complete clinical remission obtained after the initial treatment. This period is defined as the time from randomization to the first occurrence of relapse noted by the dermatologist. | 18 months after inclusion (Visit (V) 4 last visit) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Tolerance of 2 treatments | Tolerance of 2 treatments Mycoster (R) and Protocopic (R) | between 10 days and 18 months after inclusion (V3 (Day (D)10 to D180)), 30 days after inclusion (Visit D30), after 90 days after inclusion (D90) and after 120 days after inclusion (D120) and 180 days after inclusion (Visit V4) | | Number of Relapses | Number of Relapses requiring the resumption of topical corticosteroid treatment, | 180 days after inclusion (Visit V4) | | Cumulative amount of corticosteroids applied | Cumulative amount of corticosteroids applied by the patients during the study period to control their outbreaks | between 10 days and 18 months after inclusion (V3 (D10 to D180)), 30 days after inclusion (Visit D30), after 90 days after inclusion (D90) and after 120 days after inclusion (D120) and 180 days after inclusion (Visit V4) | | quality of life of patients | quality of life of patients | Inclusion (visit D0) and Last visit 180 days after inclusion (Visit D180) | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- local immunosuppressive, Maintenance therapy

NCT01900093

Evaluation of the Response to Acthar Gel Therapy in Patients Who Failed Intravenous Methylprednisolone (IVMP) for MS Relapses

Although ACTHAR gel is approved for the treatment of acute relapses, it is currently not widely used. Thus, we propose to conduct a small open-label proof-of-concept trial to evaluate the response to ACTHAR gel therapy in patients who have failed to make a satisfactory recovery after treatment with high dose IVMP. Documentation of the clinical course as well as any adverse events related to IVMP use will be made. The investigators propose to study the potential benefit of a 14-day course (the dose historically used since the landmark clinical trial of Rose et al1) of subcutaneous ACTHAR gel in 10 patients who have demonstrated inadequate improvement after a course of IVMP, 1000 mg daily, for 5 treatments (over a maximum of 8 days). These would be patients for whom PLEX would be considered as a treatment possibility. The primary outcome measure will be improvement in the targeted neurological deficit, as measured on the appropriate functional system score (FSS) of the EDSS.

This is an open-label, small, proof-of-concept study examining the safety, tolerability, and extent of recovery of a two-week course of subcutaneous Acthar Gel therapy in patients with MS relapse who have failed to make a satisfactory recovery after treatment with high dose methylprednisolone. Eligible patients will be given 80 units of Acthar for 14 days. Patients will be evaluated at baseline, at 1 week of Acthar treatment, at completion of Acthar treatment, and 1 week after completion of treatment. For those who do not undergo plasmapheresis an additional evaluation will be conducted 2 weeks after completion of treatment. Monitoring will include blood pressure determination and blood sugar determination.

An Open-Label Prospective Proof-Of-Concept Trial to Evaluate the Response to Acthar Gel Therapy in Patients With Multiple Sclerosis (MS) Relapses Who Have Failed To Make an Adequate Recovery After Treatment With High-Dose Intravenous Methylprednisolone

Multiple Sclerosis

* Drug: Acthar Gel

Inclusion Criteria:~Ages 18-65~EDSS of 2.0 - 7.5 (inclusive)~Sustained a significant MS exacerbation affecting vision, brainstem, motor, or cerebellar function AND were initially treated with a 5 day course of IVMP within 10 days of the onset of symptoms.~Failed to make adequate improvement and must initiate Acthar Gel therapy within two weeks (+/- 72 hours) after the first day of 5 treatments with 1000 mg IVMP, as judged by their treating neurologist.~Must be able to comply with the requirements of the protocol as determined by the investigator.~Ability to understand the purpose and risks of the study and provide signed and date informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.~Exclusion Criteria:~Patients whose relapse consists of pure sensory or bowel/bladder symptoms~History of ACTHAR gel use or other forms of ACTH with failure to improve or with occurrence of significant adverse experiences.~Diagnosis of scleroderma, systemic fungal infections, ocular herpes simplex, congestive heart failure, and/or uncontrolled hypertension, and/or any clinically relevant medical disease that would put the patient at risk by participating in the study~Persistent significant or severe infection~Recent history of drug or alcohol abuse~Concomitant use or prior use in the preceding 6 months of any investigational drug.~Pregnant or nursing~Recent surgery (up to the investigator's discretion what constitutes recent)~History of, or the presence of, a peptic ulcer~Known sensitivity to proteins of porcine origin~Received a live or live attenuated vaccine in the last 30 days before baseline

18 Years

65 Years

All

No

Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Improvement in Functional System Score appropriate to the Targeted Neurological Deficit | Primary outcome measure will be the percentage of patients improving by at least 1 step on the FSS appropriate to their neurological deficit (targeted neurological deficit [TND]} at 1 week following completion of treatment | at one week |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Improvement in Expanded Disability Status Scale | Secondary outcome measures will be improvement in TND at completion of ACTHAR Gel therapy, improvement by at least 1 step on EDSS at completion of treatment and at 1 week following completion of treatment. | baseline and at 1 week |

Hormones, Adrenocorticotropic Hormone, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Acthar Gel<br>80 units of subcutaneous Acthar Gel therapy daily | Drug: Acthar Gel<br>* 80 units of subcutaneous Acthar Gel therapy daily<br>* Other names: Repository corticotrophin injection;|

Evaluation of the Response to Acthar Gel Therapy in Patients Who Failed Intravenous Methylprednisolone (IVMP) for MS Relapses Study Overview ================= Brief Summary ----------------- Although ACTHAR gel is approved for the treatment of acute relapses, it is currently not widely used. Thus, we propose to conduct a small open-label proof-of-concept trial to evaluate the response to ACTHAR gel therapy in patients who have failed to make a satisfactory recovery after treatment with high dose IVMP. Documentation of the clinical course as well as any adverse events related to IVMP use will be made. The investigators propose to study the potential benefit of a 14-day course (the dose historically used since the landmark clinical trial of Rose et al1) of subcutaneous ACTHAR gel in 10 patients who have demonstrated inadequate improvement after a course of IVMP, 1000 mg daily, for 5 treatments (over a maximum of 8 days). These would be patients for whom PLEX would be considered as a treatment possibility. The primary outcome measure will be improvement in the targeted neurological deficit, as measured on the appropriate functional system score (FSS) of the EDSS. Detailed Description ----------------- This is an open-label, small, proof-of-concept study examining the safety, tolerability, and extent of recovery of a two-week course of subcutaneous Acthar Gel therapy in patients with MS relapse who have failed to make a satisfactory recovery after treatment with high dose methylprednisolone. Eligible patients will be given 80 units of Acthar for 14 days. Patients will be evaluated at baseline, at 1 week of Acthar treatment, at completion of Acthar treatment, and 1 week after completion of treatment. For those who do not undergo plasmapheresis an additional evaluation will be conducted 2 weeks after completion of treatment. Monitoring will include blood pressure determination and blood sugar determination. Official Title ----------------- An Open-Label Prospective Proof-Of-Concept Trial to Evaluate the Response to Acthar Gel Therapy in Patients With Multiple Sclerosis (MS) Relapses Who Have Failed To Make an Adequate Recovery After Treatment With High-Dose Intravenous Methylprednisolone Conditions ----------------- Multiple Sclerosis Intervention / Treatment ----------------- * Drug: Acthar Gel Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Ages 18-65 EDSS of 2.0 - 7.5 (inclusive) Sustained a significant MS exacerbation affecting vision, brainstem, motor, or cerebellar function AND were initially treated with a 5 day course of IVMP within 10 days of the onset of symptoms. Failed to make adequate improvement and must initiate Acthar Gel therapy within two weeks (+/- 72 hours) after the first day of 5 treatments with 1000 mg IVMP, as judged by their treating neurologist. Must be able to comply with the requirements of the protocol as determined by the investigator. Ability to understand the purpose and risks of the study and provide signed and date informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. Exclusion Criteria: Patients whose relapse consists of pure sensory or bowel/bladder symptoms History of ACTHAR gel use or other forms of ACTH with failure to improve or with occurrence of significant adverse experiences. Diagnosis of scleroderma, systemic fungal infections, ocular herpes simplex, congestive heart failure, and/or uncontrolled hypertension, and/or any clinically relevant medical disease that would put the patient at risk by participating in the study Persistent significant or severe infection Recent history of drug or alcohol abuse Concomitant use or prior use in the preceding 6 months of any investigational drug. Pregnant or nursing Recent surgery (up to the investigator's discretion what constitutes recent) History of, or the presence of, a peptic ulcer Known sensitivity to proteins of porcine origin Received a live or live attenuated vaccine in the last 30 days before baseline Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Acthar Gel<br>80 units of subcutaneous Acthar Gel therapy daily | Drug: Acthar Gel<br>* 80 units of subcutaneous Acthar Gel therapy daily<br>* Other names: Repository corticotrophin injection;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Improvement in Functional System Score appropriate to the Targeted Neurological Deficit | Primary outcome measure will be the percentage of patients improving by at least 1 step on the FSS appropriate to their neurological deficit (targeted neurological deficit [TND]} at 1 week following completion of treatment | at one week | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Improvement in Expanded Disability Status Scale | Secondary outcome measures will be improvement in TND at completion of ACTHAR Gel therapy, improvement by at least 1 step on EDSS at completion of treatment and at 1 week following completion of treatment. | baseline and at 1 week |

NCT02779699

A Study of AL2846 on Tolerance and Pharmacokinetics

A study of AL2846,a C-met/Hepatocyte growth factor tyrosine kinase inhibitor,in patients with advanced cancer.

To study the pharmacokinetic characteristics of AL2846 in the human body; To recommend a reasonable dose and indication for subsequent research.

Phase I Study of Tolerance and Pharmacokinetics of AL2846 in Patients With Advanced Cancer

Advanced Cancer

* Drug: AL2846

Inclusion Criteria:~Histological documentation of Advanced solid tumors（especially Hepatocellular Carcinoma and Lung Cancer ）,at least one measurable lesion (by RECIST1.1)~Lack of the standard treatment or treatment failure~18-65 years,ECOG PS:0-1,Life expectancy of more than 3 months~30 Days or more from the last cytotoxic therapy~Main organs function is normal~Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped~Patients should participate in the study voluntarily and sign informed consent~Exclusion Criteria:~Patients suffering from other malignancies currently or ever, except for cured cervical carcinoma in situ, non-melanoma skin cancers~Patients with factors that could affect oral medication (such as dysphagia，chronic diarrhea, intestinal obstruction etc.)~Patients participated in other anticancer drug clinical trials within 4 weeks or Patients participating in other clinical trials now~Blood pressure unable to be controlled ideally by one drug(systolic pressure≥140 mmHg，diastolic pressure≥90 mmHg); Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including male QTc≥450ms,female QTc≥470ms) and patients with Grade 1 or higher congestive heart failure (NYHA Classification)~Urine protein ≥ ++，and 24-hour urinary protein excretion>1.0 g confirmed~Patients with non-healing wounds or fractures~Patients with drug abuse history and unable to get rid of or Patients with mental disorders~History of immunodeficiency~Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment

18 Years

65 Years

All

No

Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The type of dose-limiting toxicity(ies) (DLT[s]) of AL2846 | Subjects within 28 days after treatment appear the following toxicity reaction relate to the drug ：II °or above of kidney damage，III °or above of non-hematological toxicity,IV°hematological toxicity ,Neutropenia associated with fever. | For 4 weeks for DLTs | | Pharmacokinetics of AL2846 (in plasma) | In the study of single-dose, full PK profiles will be obtained at H0/H0.5/H1/H2/H4/H8/H11/H24/H34/H48/H58/H72/H96/H120/H168 (H means Hour). In the study of multiple-dose, full PK profiles will be obtained at D0/D1/D4/D7/D10/D13/D15/D18/D21/D24/D28 (D means Day). | up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | | The maximum tolerated dose (MTD) of AL2846 | The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment | 48 weeks |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Objective Response Rate (ORR) | Percentage of participants with OR based assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). | each 56 days up to intolerance the toxicity or PD (up to 24 months) |

Neoplasms

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: AL2846<br>AL2846 QD po and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent | Drug: AL2846<br>* AL2846 p.o. qd<br>|

A Study of AL2846 on Tolerance and Pharmacokinetics Study Overview ================= Brief Summary ----------------- A study of AL2846,a C-met/Hepatocyte growth factor tyrosine kinase inhibitor,in patients with advanced cancer. Detailed Description ----------------- To study the pharmacokinetic characteristics of AL2846 in the human body; To recommend a reasonable dose and indication for subsequent research. Official Title ----------------- Phase I Study of Tolerance and Pharmacokinetics of AL2846 in Patients With Advanced Cancer Conditions ----------------- Advanced Cancer Intervention / Treatment ----------------- * Drug: AL2846 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Histological documentation of Advanced solid tumors（especially Hepatocellular Carcinoma and Lung Cancer ）,at least one measurable lesion (by RECIST1.1) Lack of the standard treatment or treatment failure 18-65 years,ECOG PS:0-1,Life expectancy of more than 3 months 30 Days or more from the last cytotoxic therapy Main organs function is normal Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped Patients should participate in the study voluntarily and sign informed consent Exclusion Criteria: Patients suffering from other malignancies currently or ever, except for cured cervical carcinoma in situ, non-melanoma skin cancers Patients with factors that could affect oral medication (such as dysphagia，chronic diarrhea, intestinal obstruction etc.) Patients participated in other anticancer drug clinical trials within 4 weeks or Patients participating in other clinical trials now Blood pressure unable to be controlled ideally by one drug(systolic pressure≥140 mmHg，diastolic pressure≥90 mmHg); Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including male QTc≥450ms,female QTc≥470ms) and patients with Grade 1 or higher congestive heart failure (NYHA Classification) Urine protein ≥ ++，and 24-hour urinary protein excretion>1.0 g confirmed Patients with non-healing wounds or fractures Patients with drug abuse history and unable to get rid of or Patients with mental disorders History of immunodeficiency Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: AL2846<br>AL2846 QD po and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent | Drug: AL2846<br>* AL2846 p.o. qd<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The type of dose-limiting toxicity(ies) (DLT[s]) of AL2846 | Subjects within 28 days after treatment appear the following toxicity reaction relate to the drug ：II °or above of kidney damage，III °or above of non-hematological toxicity,IV°hematological toxicity ,Neutropenia associated with fever. | For 4 weeks for DLTs | | Pharmacokinetics of AL2846 (in plasma) | In the study of single-dose, full PK profiles will be obtained at H0/H0.5/H1/H2/H4/H8/H11/H24/H34/H48/H58/H72/H96/H120/H168 (H means Hour). In the study of multiple-dose, full PK profiles will be obtained at D0/D1/D4/D7/D10/D13/D15/D18/D21/D24/D28 (D means Day). | up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | | The maximum tolerated dose (MTD) of AL2846 | The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment | 48 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Objective Response Rate (ORR) | Percentage of participants with OR based assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). | each 56 days up to intolerance the toxicity or PD (up to 24 months) |

NCT03487159

Using the Non Invasive Technology Magnetic Resonance Elastography for the Diagnosis of Liver Fibrosis Stage

This study evaluates the ability of Magnetic Resonance Elastography non invasive technology to identify the liver fibrosis stage in patients with chronic liver diseases compared to Shear Wave Elastography and/or Liver Biopsy.

Recent advances in magnetic resonance imaging (MRI) of the liver have led to improvements in diagnosis of chronic liver diseases. Detection and staging of liver fibrosis has become important; however, until about the last decade, it depended on an invasive liver biopsy. Liver biopsy is limited by high cost, low patient acceptance, interobserver variability during microscopic evaluation, sampling error, poor reproducibility, and, importantly, an invasive nature with a complication rate of 3% and a mortality rate of 0.03%. With the emergence of elastography techniques, the need for liver biopsy has rapidly diminished for diagnosis of clinically significant liver fibrosis. Magnetic Resonance Elastography has gained increasing popularity in recent years, in large part due to its higher technical success and ability to overcome some of the weaknesses of ultrasound-based methods for assessing liver fibrosis.

Using the Non Invasive Technology Magnetic Resonance Elastography for the Diagnosis of Liver Fibrosis Stage

Liver Diseases

* Device: MRE (Magnetic Resonance Elastography)

Inclusion Criteria:~Patients with chronic liver diseases~Exclusion Criteria:~Patients who don't have chronic liver diseases

18 Years

100 Years

All

No

Primary Purpose: Diagnostic Allocation: Non-Randomized Intervention Model: Parallel Assignment Interventional Model Description: The study model includes 2 study arms:~Patients with chronic liver diseases who will undergo a routine liver biopsy, Shear Wave elastography and the MRE in order to evaluate the liver fibrosis stage.~Patients with chronic liver diseases who will undergo a routine Shear Wave elastography and the MRE in order to evaluate the liver fibrosis stage.~Demographic and clinical information will be collected from the patient's medical files. Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Liver Biopsy Result for liver fibrosis grade | Liver Fibrosis score measured by Metavir scale .The Metavir score grades the degree of fibrosis on a 5-point scale from 0 to 4. The activity, which is the amount of inflammation (specifically, the intensity of necro-inflammatory lesions), is graded on a 4-point scale from A0 to A3.~Fibrosis score:~F0 = no fibrosis F1 = portal fibrosis without septa F2 = portal fibrosis with few septa F3 = numerous septa without cirrhosis F4 = cirrhosis~Activity score:~A0 = no activity A1 = mild activity A2 = moderate activity A3 = severe activity Liver biopsy will be perfomed only according to physician recommendation. | Patient will undergo Liver biopsy once during 1 year of the study. | | Magnetic Resonance Elastography (MRE) Result for liver fibrosis grade | Liver Fibrosis score determined by liver stiffness in 4 fibrosis grades: >1=any fibrosis, >2=significant fibrosis, >3=advanced fibrosis, 4=cirrhosis | Patient will undergo Magnetic Resonance Elastography (MRE) once during 1 year of the study. | | Shear Wave Elastography Result for liver fibrosis grade | Liver Fibrosis score determined by liver stiffness in in 5 fibrosis grades: 0=no fibrosis, >1=any fibrosis, >2=significant fibrosis, >3=advanced fibrosis, 4=cirrhosis | Patient will undergo Shear Wave Elastography once during 1 year of the study. |

Liver Diseases, Liver Cirrhosis, Fibrosis, Pathologic Processes, Digestive System Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: Liver biopsy ,Elastography and MRE<br>Performance of routine Liver biopsy,Shear Wave Elastography and investigational MRE (Magnetic Resonance Elastography) in order to evaluate liver fibrosis stage. | Device: MRE (Magnetic Resonance Elastography)<br>* The device is using to evaluate liver fibrosis stage<br>| | Other: Elastography and MRE<br>Performance of routine Shear Wave Elastography and investigational MRE (Magnetic Resonance Elastography) in order to evaluate liver fibrosis stage. | Device: MRE (Magnetic Resonance Elastography)<br>* The device is using to evaluate liver fibrosis stage<br>|

Using the Non Invasive Technology Magnetic Resonance Elastography for the Diagnosis of Liver Fibrosis Stage Study Overview ================= Brief Summary ----------------- This study evaluates the ability of Magnetic Resonance Elastography non invasive technology to identify the liver fibrosis stage in patients with chronic liver diseases compared to Shear Wave Elastography and/or Liver Biopsy. Detailed Description ----------------- Recent advances in magnetic resonance imaging (MRI) of the liver have led to improvements in diagnosis of chronic liver diseases. Detection and staging of liver fibrosis has become important; however, until about the last decade, it depended on an invasive liver biopsy. Liver biopsy is limited by high cost, low patient acceptance, interobserver variability during microscopic evaluation, sampling error, poor reproducibility, and, importantly, an invasive nature with a complication rate of 3% and a mortality rate of 0.03%. With the emergence of elastography techniques, the need for liver biopsy has rapidly diminished for diagnosis of clinically significant liver fibrosis. Magnetic Resonance Elastography has gained increasing popularity in recent years, in large part due to its higher technical success and ability to overcome some of the weaknesses of ultrasound-based methods for assessing liver fibrosis. Official Title ----------------- Using the Non Invasive Technology Magnetic Resonance Elastography for the Diagnosis of Liver Fibrosis Stage Conditions ----------------- Liver Diseases Intervention / Treatment ----------------- * Device: MRE (Magnetic Resonance Elastography) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients with chronic liver diseases Exclusion Criteria: Patients who don't have chronic liver diseases Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 100 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Diagnostic Allocation: Non-Randomized Intervention Model: Parallel Assignment Interventional Model Description: The study model includes 2 study arms: Patients with chronic liver diseases who will undergo a routine liver biopsy, Shear Wave elastography and the MRE in order to evaluate the liver fibrosis stage. Patients with chronic liver diseases who will undergo a routine Shear Wave elastography and the MRE in order to evaluate the liver fibrosis stage. Demographic and clinical information will be collected from the patient's medical files. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: Liver biopsy ,Elastography and MRE<br>Performance of routine Liver biopsy,Shear Wave Elastography and investigational MRE (Magnetic Resonance Elastography) in order to evaluate liver fibrosis stage. | Device: MRE (Magnetic Resonance Elastography)<br>* The device is using to evaluate liver fibrosis stage<br>| | Other: Elastography and MRE<br>Performance of routine Shear Wave Elastography and investigational MRE (Magnetic Resonance Elastography) in order to evaluate liver fibrosis stage. | Device: MRE (Magnetic Resonance Elastography)<br>* The device is using to evaluate liver fibrosis stage<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Liver Biopsy Result for liver fibrosis grade | Liver Fibrosis score measured by Metavir scale .The Metavir score grades the degree of fibrosis on a 5-point scale from 0 to 4. The activity, which is the amount of inflammation (specifically, the intensity of necro-inflammatory lesions), is graded on a 4-point scale from A0 to A3. Fibrosis score: F0 = no fibrosis F1 = portal fibrosis without septa F2 = portal fibrosis with few septa F3 = numerous septa without cirrhosis F4 = cirrhosis Activity score: A0 = no activity A1 = mild activity A2 = moderate activity A3 = severe activity Liver biopsy will be perfomed only according to physician recommendation. | Patient will undergo Liver biopsy once during 1 year of the study. | | Magnetic Resonance Elastography (MRE) Result for liver fibrosis grade | Liver Fibrosis score determined by liver stiffness in 4 fibrosis grades: >1=any fibrosis, >2=significant fibrosis, >3=advanced fibrosis, 4=cirrhosis | Patient will undergo Magnetic Resonance Elastography (MRE) once during 1 year of the study. | | Shear Wave Elastography Result for liver fibrosis grade | Liver Fibrosis score determined by liver stiffness in in 5 fibrosis grades: 0=no fibrosis, >1=any fibrosis, >2=significant fibrosis, >3=advanced fibrosis, 4=cirrhosis | Patient will undergo Shear Wave Elastography once during 1 year of the study. |

NCT00094068

The Effect of Sildenafil Citrate (Viagra® (Registered Trademark)) on Brain Blood Flow in Multiple Sclerosis Patients

This study will determine whether sildenafil citrate, commonly known as Viagra, can cause increased blood flow to the brain in a wide range of multiple sclerosis (MS) patients, including women. Although people with MS can have reduced blood flow in the brain as part of the disease process, it has been observed that men with MS may have increased blood flow to the brain while taking sildenafil citrate. This study will measure brain blood flow or blood volume in men and women with MS before and after taking Viagra and compare the results to those in healthy volunteers in an effort to better understand the disease.~Healthy volunteers 18 years of age and older and patients with MS between 18 and 55 years of age may be eligible for this study. Volunteers are screened with a medical history and physical examination, and patients with MS are evaluated with a complete neurological examination and screening for heart disease, including history of chest pain, heart attack, and use of nitrates.~Participants undergo magnetic resonance imaging (MRI) before and after taking Viagra. During the scanning, subjects lie still on a table that can slide in and out of the cylindrical metal scanner. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45 and 90 minutes. First, a scan is obtained of the carotid arteries (major arteries in the neck supplying blood to the brain) to determine if the arteries are narrowed, and then baseline MRI scans and measures of brain blood flow are obtained. The subject then comes out of the scanner and takes a Viagra pill. After 1 hour, the subject returns to the scanner and more scans are obtained to determine changes in brain blood flow and blood volume following Viagra.~A catheter (thin plastic tube) is placed in the subject's arm before he or she enters the magnet for the second time for injection of a contrast agent called gadolinium DTPA, which allows brain structures to be distinguished more clearly.

Advances in MR perfusion imaging have provided clinical researchers with the opportunity to quantify regional cerebral blood flow (CBF). It has been shown that cerebral perfusion in patients with multiple sclerosis (MS) is reduced, particularly in the grey matter. However, preliminary data in a small number of male secondary progressive (SP) MS patients with erectile dysfunction suggests that sildenafil citrate (Viagra® (Registered Trademark)) helps to increase grey matter perfusion. The purpose of this study is to extend these findings to male MS patients without erectile dysfunction and female MS patients by comparing CBF measures of MS patients of both sexes, to age and gender-matched healthy controls. CBF will be measured before and one hour after taking sildenafil citrate.

A Pilot Study to Detect the Effect of Sildenafil Citrate on Cerebral Blood Perfusion in Multiple Sclerosis Patients by Perfusion MRI

Multiple Sclerosis

INCLUSION CRITERIA:~Any healthy normal volunteer above the age of 18 who is capable of giving informed consent recruited or self referred through the NIH Volunteer office will be eligible for this study.~All healthy normal volunteers will be included as long as there is no recorded or documented signs or symptoms of CNS disease, contraindications to a MRI and have a normal age appropriate MRI of the brain.~Patients seen in the Neuroimmunology MS clinic with a confirmed diagnosis of Multiple Sclerosis based upon previous history of two clinical neurological attacks separated in time and in spatial location or combination of Clinical and MRI findings of a single enhancing lesion in the brain or spine along with multiple T2 hyperintensities in the juxtacortical, periventricular or infratentorial white matter according to the McDonald criteria will be included in this study.~Relapsing-remitting or secondary progressive MS who have had more than one relapse within 18 months preceding study enrollment will be recruited from the MS 7th floor clinic in the NINDS at the NIH. MS patients will have EDSS score between 1.0 - 6.5, inclusive. MS patients seen and treated in the NINDS MS clinic are representative of the general MS population that is Female: male ratio of approximately 3:2, Caucasian and African American, between ages of 18-55 years old.~Give written informed consent prior to any testing under this protocol, including screening/pre-treatment tests and evaluations that are not considered part of the patient's routine care.~EXCLUSION CRITERIA:~Healthy Controls and MS patients will be excluded if they have contraindications to MR scanning, such as the following:~aneurysm clip~implanted neural stimulator~implanted cardiac pacemaker or autodefibrillator~cochlear implant~ocular foreign body (e.g., metal shavings)~insulin pump~Healthy controls and MS patients will be excluded from this study if they have the following:~History of heart attack~History of treatment with nitrates for heart condition~History of carotid artery stenosis or evidence of greater than 50% carotid stenosis on screening MR angiogram~History of known vascular disease~History of stroke~History of migraine~Subjects who have a history of a reaction to MR contrast agents specifically gadopentetate dimeglumine will be excluded from participating in the contrast agent administration part of this protocol.~Healthy controls will be excluded if have history of alcohol or drug abuse.~Healthy controls will be excluded if Concurrent, clinically significant (as determined by the investigator) gastrointestinal, immunologic, pulmonary, neurologic, renal, and/or other major disease.~Healthy controls will be excluded if they have a previous known abnormality on Brain MRI examination.~Pregnant and lactating women will be excluded from the study.~Since certain drugs may interfere with the ability of the vessels in your brain to respond to Viagra, subjects taking steroids or sildenafil (within 24 hours) will be excluded from this study.~MS patients will also be excluded from study entry if any of the following exclusion criteria exist at the time of enrollment:~Pregnant and lactating women who are MS patients will be excluded from the study.~Diagnosis of primary progressive MS, defined as gradual progression of disability from the onset without relapses.~Concurrent, clinically significant (as determined by the investigator) immunologic, pulmonary, gastrointestinal, neurologic, renal, and/or other major disease in MS patients.~Treatment History in MS patients~If prior treatment with steroids was received, the subject must have been off treatment for the required period prior to enrollment (see below).~Agent: Corticosteroids~Time Required off Agent Prior to Enrollment: 8 weeks~Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's returning for follow-up visits to the NINDS, Neuroimmunology Clinic will be sufficient reason to exclude a subject.

All

Accepts Healthy Volunteers

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- |

Lesion, Gray Matter, White Matter, Cerebral Blood Flow, Cerebral Blood Volume, MRI, Multiple Sclerosis, Perfusion, Imaging, Sildenafil, MS, Healthy Volunteer, HV

Multiple Sclerosis, Sclerosis, Pathologic Processes, Demyelinating Autoimmune Diseases, CNS, Autoimmune Diseases of the Nervous System, Nervous System Diseases, Demyelinating Diseases, Autoimmune Diseases, Immune System Diseases

The Effect of Sildenafil Citrate (Viagra® (Registered Trademark)) on Brain Blood Flow in Multiple Sclerosis Patients Study Overview ================= Brief Summary ----------------- This study will determine whether sildenafil citrate, commonly known as Viagra, can cause increased blood flow to the brain in a wide range of multiple sclerosis (MS) patients, including women. Although people with MS can have reduced blood flow in the brain as part of the disease process, it has been observed that men with MS may have increased blood flow to the brain while taking sildenafil citrate. This study will measure brain blood flow or blood volume in men and women with MS before and after taking Viagra and compare the results to those in healthy volunteers in an effort to better understand the disease. Healthy volunteers 18 years of age and older and patients with MS between 18 and 55 years of age may be eligible for this study. Volunteers are screened with a medical history and physical examination, and patients with MS are evaluated with a complete neurological examination and screening for heart disease, including history of chest pain, heart attack, and use of nitrates. Participants undergo magnetic resonance imaging (MRI) before and after taking Viagra. During the scanning, subjects lie still on a table that can slide in and out of the cylindrical metal scanner. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45 and 90 minutes. First, a scan is obtained of the carotid arteries (major arteries in the neck supplying blood to the brain) to determine if the arteries are narrowed, and then baseline MRI scans and measures of brain blood flow are obtained. The subject then comes out of the scanner and takes a Viagra pill. After 1 hour, the subject returns to the scanner and more scans are obtained to determine changes in brain blood flow and blood volume following Viagra. A catheter (thin plastic tube) is placed in the subject's arm before he or she enters the magnet for the second time for injection of a contrast agent called gadolinium DTPA, which allows brain structures to be distinguished more clearly. Detailed Description ----------------- Advances in MR perfusion imaging have provided clinical researchers with the opportunity to quantify regional cerebral blood flow (CBF). It has been shown that cerebral perfusion in patients with multiple sclerosis (MS) is reduced, particularly in the grey matter. However, preliminary data in a small number of male secondary progressive (SP) MS patients with erectile dysfunction suggests that sildenafil citrate (Viagra® (Registered Trademark)) helps to increase grey matter perfusion. The purpose of this study is to extend these findings to male MS patients without erectile dysfunction and female MS patients by comparing CBF measures of MS patients of both sexes, to age and gender-matched healthy controls. CBF will be measured before and one hour after taking sildenafil citrate. Official Title ----------------- A Pilot Study to Detect the Effect of Sildenafil Citrate on Cerebral Blood Perfusion in Multiple Sclerosis Patients by Perfusion MRI Conditions ----------------- Multiple Sclerosis Participation Criteria ================= Eligibility Criteria ----------------- INCLUSION CRITERIA: Any healthy normal volunteer above the age of 18 who is capable of giving informed consent recruited or self referred through the NIH Volunteer office will be eligible for this study. All healthy normal volunteers will be included as long as there is no recorded or documented signs or symptoms of CNS disease, contraindications to a MRI and have a normal age appropriate MRI of the brain. Patients seen in the Neuroimmunology MS clinic with a confirmed diagnosis of Multiple Sclerosis based upon previous history of two clinical neurological attacks separated in time and in spatial location or combination of Clinical and MRI findings of a single enhancing lesion in the brain or spine along with multiple T2 hyperintensities in the juxtacortical, periventricular or infratentorial white matter according to the McDonald criteria will be included in this study. Relapsing-remitting or secondary progressive MS who have had more than one relapse within 18 months preceding study enrollment will be recruited from the MS 7th floor clinic in the NINDS at the NIH. MS patients will have EDSS score between 1.0 - 6.5, inclusive. MS patients seen and treated in the NINDS MS clinic are representative of the general MS population that is Female: male ratio of approximately 3:2, Caucasian and African American, between ages of 18-55 years old. Give written informed consent prior to any testing under this protocol, including screening/pre-treatment tests and evaluations that are not considered part of the patient's routine care. EXCLUSION CRITERIA: Healthy Controls and MS patients will be excluded if they have contraindications to MR scanning, such as the following: aneurysm clip implanted neural stimulator implanted cardiac pacemaker or autodefibrillator cochlear implant ocular foreign body (e.g., metal shavings) insulin pump Healthy controls and MS patients will be excluded from this study if they have the following: History of heart attack History of treatment with nitrates for heart condition History of carotid artery stenosis or evidence of greater than 50% carotid stenosis on screening MR angiogram History of known vascular disease History of stroke History of migraine Subjects who have a history of a reaction to MR contrast agents specifically gadopentetate dimeglumine will be excluded from participating in the contrast agent administration part of this protocol. Healthy controls will be excluded if have history of alcohol or drug abuse. Healthy controls will be excluded if Concurrent, clinically significant (as determined by the investigator) gastrointestinal, immunologic, pulmonary, neurologic, renal, and/or other major disease. Healthy controls will be excluded if they have a previous known abnormality on Brain MRI examination. Pregnant and lactating women will be excluded from the study. Since certain drugs may interfere with the ability of the vessels in your brain to respond to Viagra, subjects taking steroids or sildenafil (within 24 hours) will be excluded from this study. MS patients will also be excluded from study entry if any of the following exclusion criteria exist at the time of enrollment: Pregnant and lactating women who are MS patients will be excluded from the study. Diagnosis of primary progressive MS, defined as gradual progression of disability from the onset without relapses. Concurrent, clinically significant (as determined by the investigator) immunologic, pulmonary, gastrointestinal, neurologic, renal, and/or other major disease in MS patients. Treatment History in MS patients If prior treatment with steroids was received, the subject must have been off treatment for the required period prior to enrollment (see below). Agent: Corticosteroids Time Required off Agent Prior to Enrollment: 8 weeks Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's returning for follow-up visits to the NINDS, Neuroimmunology Clinic will be sufficient reason to exclude a subject. Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Lesion, Gray Matter, White Matter, Cerebral Blood Flow, Cerebral Blood Volume, MRI, Multiple Sclerosis, Perfusion, Imaging, Sildenafil, MS, Healthy Volunteer, HV

NCT05344885

A Pilot Trial Examining Digital Parent Training Programs

The purpose of this pilot study is to preliminary examine the impact of a design mechanism aimed at increasing engagement in an unguided digital parent training program for child's behavior problems. Parents will be enrolled into one of two digital parent training intervention arms, dedifferentiated by their level of correspondence with the related deign mechanism.

The purpose of this pilot study is to preliminary examine the impact of a design mechanism aimed at increasing engagement in an unguided digital parent training program for child's behavior problems. The design mechanism manipulated in this pilot relates to the extent to which program design promotes a positive behavior change. To achieve these goal two unguided digital parent training interventions, differentiated by their level of design (DPT-Standard vs. DPT-Enhanced), will be tested. This pilot aims to recruit 40-60 parents who report behavior problems in their children who will randomly receive one of the two interventions for 10 weeks.~The impact of DPT-E on user engagement and reported child behavior problems will be assessed based on comparison with DPT-Standard. Parental behaviors and sense of competence will be collected to assess the impact of intervention design on these mechanisms of change. In addition, the role of parents' motivation, and their ability to invest effort in making changes during the intervention will be assessed, to examine whether these variables moderate the impact of intervention's design on the aforementioned relationships. The investigators also aim to explore whether the relationship between usage and clinical outcomes is stronger in those using DPT-E compared with DPT-Standard.

Examining the Impact of Intervention Design in Digital Parent Training for Child's Disruptive Behaviors: A Pilot Randomized Trial

Child Behavior Problem, Parenting, Engagement, Patient

* Behavioral: DPT-Standard * Behavioral: DPT-Enhanced

Inclusion Criteria:~Parents report they have a child between the ages of 3 and 7, who:~Has externalized behavior problems based on A) Parents report at least 1 of the two first criteria of behavior problems to be above 4 (the middle point) & the average of all items ≥ 4, on a screening scale that consists of 9 items (on a Likert scale between 1 and 7) that is based on DSM-V symptoms for ODD.~B) Parents report ECBI Problems to be above 14 OR Intensity to be above 130.~Parents have access to computer at home with an Internet connection and a smartphone with a mobile data plan.~Parents can read and understand Hebrew.~Exclusion Criteria:~Parents report that the relevant child has been diagnosed with developmental delay, intellectual disability and/or autism spectrum disorder.~Parent and/or child are already receiving therapeutic intervention (for the child) in other setting.~The relevant child is treated with psychiatric medication.

3 Years

7 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline Eyberg Child Behavior Inventory (ECBI) at 10 weeks | The ECBI specifies 36 behaviors commonly reported by parents of children with behavior problems. For each behavior the parent specifies how often this problem occurs on a 1-7 Likert scale (1=never; 7=always; higher scores mean worse outcome), and whether this behavior is currently a problem (0=no; 1=yes; higher scores mean worse outcome). | 10 weeks |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | change from Baseline Behavior and Feelings Survey Externalizing Problems at 10 weeks | The Behavior and Feelings Survey (BFS) parent report of Externalizing Problems in children and adolescents is based on summing 6 items that measure children's behavior problems on a 0-4 scale (0=not a problem; 4=a very big problem). | 10 weeks | | change from Baseline Parenting Scale (PS) at 10 weeks | Two sub-scales of the Parenting Scale, Over-reactivity (11 items) and Laxness (10 items) will be used in this study. The parent is requested to mark his typical response on a 7-point Likert scale (1-7), when 7 indicates the ineffective spectrum (higher scores mean worse outcome), and 1 indicates the effective spectrum. | 10 weeks | | change from Baseline Alabama Parenting Questionnaire (APQ) positive parenting practices at 10 weeks | 3 items, 1 sub-scale: measuring positive parenting practices. Parents will be asked to mark the frequency they use each parental practice on a 5-point scale ranging from 1 (never) to 5 (always; higher scores mean better outcome). | 10 weeks | | change from Baseline Me as a Parent (MAAP) self-efficacy at 10 weeks | 4 items, 1 sub-scale measures general parental self-efficacy. Responses range on a 5-point Likert scale from 1 = strongly disagree to 5 = strongly agree (higher scores mean better outcome). | 10 weeks | | change from Baseline Parenting Tasks Checklist (PTC) self-efficacy at 10 weeks | 12 items, 2 sub-scales: behavioral self-efficacy (6 items), setting self-efficacy (6 items). Parents are asked to rate each item on a scale ranges from 0 to 100 (0=Certain I can't do it, 100=Certain I can do it; higher scores mean better outcome). | 10 weeks | | Program Usage Time | Time on the platform (measured in minutes) | through program completion, an average of 10 weeks | | Program Logins | Number of user logins to the platform | through program completion, an average of 10 weeks | | Number of Modules completed | The number of program Modules that were completed while using the program | through program completion, an average of 10 weeks |

Problem Behavior, Behavioral Symptoms

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: DPT-standard<br>A standard digital parent training intervention | Behavioral: DPT-Standard<br>* The parent training intervention includes 7 modules, recommended to be completed within 7- to 10-weeks period. Module's content includes videos and texts guiding the parent through the training process; interactive features, such as multiple-choice questions with direct feedback. Additional features embedded within the platform include downloadable materials, and a Q&A section that contains frequently asked questions.<br>| | Experimental: DPT-Enhanced<br>Enhanced digital parent training intervention | Behavioral: DPT-Enhanced<br>* DPT-Enhanced will include all the ingredients of DPT-Standard, but with additional features. The program itself is based on pre-defined decision rules that are either event or time based based on evidence based practice in promoting effective parental engagement. Each component includes a short learning phase, followed by a 1-2 week focusing phase. The focusing phase is designed to encourage and help parents to practice and acquire learned skills in their day-to-day lives, by making these skills more salient in their mind.<br>|

A Pilot Trial Examining Digital Parent Training Programs Study Overview ================= Brief Summary ----------------- The purpose of this pilot study is to preliminary examine the impact of a design mechanism aimed at increasing engagement in an unguided digital parent training program for child's behavior problems. Parents will be enrolled into one of two digital parent training intervention arms, dedifferentiated by their level of correspondence with the related deign mechanism. Detailed Description ----------------- The purpose of this pilot study is to preliminary examine the impact of a design mechanism aimed at increasing engagement in an unguided digital parent training program for child's behavior problems. The design mechanism manipulated in this pilot relates to the extent to which program design promotes a positive behavior change. To achieve these goal two unguided digital parent training interventions, differentiated by their level of design (DPT-Standard vs. DPT-Enhanced), will be tested. This pilot aims to recruit 40-60 parents who report behavior problems in their children who will randomly receive one of the two interventions for 10 weeks. The impact of DPT-E on user engagement and reported child behavior problems will be assessed based on comparison with DPT-Standard. Parental behaviors and sense of competence will be collected to assess the impact of intervention design on these mechanisms of change. In addition, the role of parents' motivation, and their ability to invest effort in making changes during the intervention will be assessed, to examine whether these variables moderate the impact of intervention's design on the aforementioned relationships. The investigators also aim to explore whether the relationship between usage and clinical outcomes is stronger in those using DPT-E compared with DPT-Standard. Official Title ----------------- Examining the Impact of Intervention Design in Digital Parent Training for Child's Disruptive Behaviors: A Pilot Randomized Trial Conditions ----------------- Child Behavior Problem, Parenting, Engagement, Patient Intervention / Treatment ----------------- * Behavioral: DPT-Standard * Behavioral: DPT-Enhanced Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Parents report they have a child between the ages of 3 and 7, who: Has externalized behavior problems based on A) Parents report at least 1 of the two first criteria of behavior problems to be above 4 (the middle point) & the average of all items ≥ 4, on a screening scale that consists of 9 items (on a Likert scale between 1 and 7) that is based on DSM-V symptoms for ODD. B) Parents report ECBI Problems to be above 14 OR Intensity to be above 130. Parents have access to computer at home with an Internet connection and a smartphone with a mobile data plan. Parents can read and understand Hebrew. Exclusion Criteria: Parents report that the relevant child has been diagnosed with developmental delay, intellectual disability and/or autism spectrum disorder. Parent and/or child are already receiving therapeutic intervention (for the child) in other setting. The relevant child is treated with psychiatric medication. Ages Eligible for Study ----------------- Minimum Age: 3 Years Maximum Age: 7 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: DPT-standard<br>A standard digital parent training intervention | Behavioral: DPT-Standard<br>* The parent training intervention includes 7 modules, recommended to be completed within 7- to 10-weeks period. Module's content includes videos and texts guiding the parent through the training process; interactive features, such as multiple-choice questions with direct feedback. Additional features embedded within the platform include downloadable materials, and a Q&A section that contains frequently asked questions.<br>| | Experimental: DPT-Enhanced<br>Enhanced digital parent training intervention | Behavioral: DPT-Enhanced<br>* DPT-Enhanced will include all the ingredients of DPT-Standard, but with additional features. The program itself is based on pre-defined decision rules that are either event or time based based on evidence based practice in promoting effective parental engagement. Each component includes a short learning phase, followed by a 1-2 week focusing phase. The focusing phase is designed to encourage and help parents to practice and acquire learned skills in their day-to-day lives, by making these skills more salient in their mind.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline Eyberg Child Behavior Inventory (ECBI) at 10 weeks | The ECBI specifies 36 behaviors commonly reported by parents of children with behavior problems. For each behavior the parent specifies how often this problem occurs on a 1-7 Likert scale (1=never; 7=always; higher scores mean worse outcome), and whether this behavior is currently a problem (0=no; 1=yes; higher scores mean worse outcome). | 10 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | change from Baseline Behavior and Feelings Survey Externalizing Problems at 10 weeks | The Behavior and Feelings Survey (BFS) parent report of Externalizing Problems in children and adolescents is based on summing 6 items that measure children's behavior problems on a 0-4 scale (0=not a problem; 4=a very big problem). | 10 weeks | | change from Baseline Parenting Scale (PS) at 10 weeks | Two sub-scales of the Parenting Scale, Over-reactivity (11 items) and Laxness (10 items) will be used in this study. The parent is requested to mark his typical response on a 7-point Likert scale (1-7), when 7 indicates the ineffective spectrum (higher scores mean worse outcome), and 1 indicates the effective spectrum. | 10 weeks | | change from Baseline Alabama Parenting Questionnaire (APQ) positive parenting practices at 10 weeks | 3 items, 1 sub-scale: measuring positive parenting practices. Parents will be asked to mark the frequency they use each parental practice on a 5-point scale ranging from 1 (never) to 5 (always; higher scores mean better outcome). | 10 weeks | | change from Baseline Me as a Parent (MAAP) self-efficacy at 10 weeks | 4 items, 1 sub-scale measures general parental self-efficacy. Responses range on a 5-point Likert scale from 1 = strongly disagree to 5 = strongly agree (higher scores mean better outcome). | 10 weeks | | change from Baseline Parenting Tasks Checklist (PTC) self-efficacy at 10 weeks | 12 items, 2 sub-scales: behavioral self-efficacy (6 items), setting self-efficacy (6 items). Parents are asked to rate each item on a scale ranges from 0 to 100 (0=Certain I can't do it, 100=Certain I can do it; higher scores mean better outcome). | 10 weeks | | Program Usage Time | Time on the platform (measured in minutes) | through program completion, an average of 10 weeks | | Program Logins | Number of user logins to the platform | through program completion, an average of 10 weeks | | Number of Modules completed | The number of program Modules that were completed while using the program | through program completion, an average of 10 weeks |

NCT00524199

Effects of Mesna on Homocysteine in Kidney Failure

The purpose of this research study is to examine the effect of a drug called mesna on the removal of homocysteine from blood during dialysis. Homocysteine is an amino acid (protein building block) found in the blood of all people, however it is considerably elevated in dialysis patients. People with increased levels of homocysteine in their blood are at increased risk of developing plaque buildup in their arteries and other related problems such as heart attack and stroke. This study will determine if mesna can improve the rate of homocysteine removal from blood during dialysis.

Homocysteine is a thiol amino acid derived from dietary methionine. Elevated plasma total homocysteine (tHcy), termed hyperhomocysteinemia, is a graded, independent risk factor for the development of atherosclerosis. Elevated plasma tHcy can be normalized by supplementation with folic acid and vitamins B6 and B12 in most patients with normal renal function and this treatment has been shown to halt the progression of atherosclerotic plaque.~Over 90% of patients with end-stage renal disease (ESRD) requiring hemodialysis have elevated plasma tHcy. The leading causes of morbidity and mortality in these patients are cardiovascular-related pathologies such as myocardial infarction and stroke. Vitamin supplementation consistently fails to normalize elevated plasma tHcy in patients with ESRD, thus leaving them at increased risk. Plasma tHcy is 70 - 80% covalently protein bound limiting the effectiveness of dialysis as a tHcy lowering treatment.~Mesna (sodium 2-mercaptoethanesulfonic acid) is a thiol-containing drug currently indicated to prevent hemorrhagic cystitis associated with ifosfamide chemotherapy. Mesna has incidentally been shown to deplete plasma thiols in cancer patients undergoing ifosfamide chemotherapy. Mesna acts to exchange with thiols bound to plasma proteins enhancing their renal excretion. In vitro studies in our laboratory have shown that mesna rapidly (within 5 minutes) exchanges with protein bound homocysteine yielding a significantly larger dialyzable fraction of the thiol amino acid.~A pilot study recently completed by our group demonstrated a significant decrease in tHcy in eight hemodialysis patients receiving 12 mg/kg mesna three times a week pre-dialysis for one week. Although this therapy did cause a significant decline in tHcy, mesna failed to reduce tHcy to normal levels. The cumulative effects of mesna administration over a longer treatment period should be evaluated.

The Effects of 12 mg/kg Intravenous Mesna on Plasma Total Homocysteine Concentration in Patients With End-stage Renal Disease Requiring Hemodialysis

End Stage Renal Disease

* Drug: Mesna * Other: Saline

Inclusion Criteria:~Patients with end-stage renal disease who have received hemodialysis thrice weekly for at least 90 days~Serum albumin > 30 g/L.~Exclusion Criteria:~Patients who refuse to sign a letter of informed consent~Women who are or are trying to become pregnant or are breast-feeding.

18 Years

80 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: Quadruple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Difference in plasma total homocysteine between placebo and mesna treatments | | Four weeks |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Excretion of mesna during hemodialysis | | duration of dialytic session |

homocysteine, hemodialysis, mesna

Mesna, Protective Agents, Physiological Effects of Drugs

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: Placebo<br>Saline IV infusion over five minutes at the beginning of dialysis. | Other: Saline<br>* Saline IV infusion over five minutes at the beginning of dialysis thrice weekly.<br>| | Active Comparator: Mesna<br>12 mg/kg mesna IV infusion over five minutes at the beginning of dialysis. | Drug: Mesna<br>* 12 mg/kg IV infusion over five minutes at the beginning of dialysis thrice weekly.<br>* Other names: Uromitexan;|

Effects of Mesna on Homocysteine in Kidney Failure Study Overview ================= Brief Summary ----------------- The purpose of this research study is to examine the effect of a drug called mesna on the removal of homocysteine from blood during dialysis. Homocysteine is an amino acid (protein building block) found in the blood of all people, however it is considerably elevated in dialysis patients. People with increased levels of homocysteine in their blood are at increased risk of developing plaque buildup in their arteries and other related problems such as heart attack and stroke. This study will determine if mesna can improve the rate of homocysteine removal from blood during dialysis. Detailed Description ----------------- Homocysteine is a thiol amino acid derived from dietary methionine. Elevated plasma total homocysteine (tHcy), termed hyperhomocysteinemia, is a graded, independent risk factor for the development of atherosclerosis. Elevated plasma tHcy can be normalized by supplementation with folic acid and vitamins B6 and B12 in most patients with normal renal function and this treatment has been shown to halt the progression of atherosclerotic plaque. Over 90% of patients with end-stage renal disease (ESRD) requiring hemodialysis have elevated plasma tHcy. The leading causes of morbidity and mortality in these patients are cardiovascular-related pathologies such as myocardial infarction and stroke. Vitamin supplementation consistently fails to normalize elevated plasma tHcy in patients with ESRD, thus leaving them at increased risk. Plasma tHcy is 70 - 80% covalently protein bound limiting the effectiveness of dialysis as a tHcy lowering treatment. Mesna (sodium 2-mercaptoethanesulfonic acid) is a thiol-containing drug currently indicated to prevent hemorrhagic cystitis associated with ifosfamide chemotherapy. Mesna has incidentally been shown to deplete plasma thiols in cancer patients undergoing ifosfamide chemotherapy. Mesna acts to exchange with thiols bound to plasma proteins enhancing their renal excretion. In vitro studies in our laboratory have shown that mesna rapidly (within 5 minutes) exchanges with protein bound homocysteine yielding a significantly larger dialyzable fraction of the thiol amino acid. A pilot study recently completed by our group demonstrated a significant decrease in tHcy in eight hemodialysis patients receiving 12 mg/kg mesna three times a week pre-dialysis for one week. Although this therapy did cause a significant decline in tHcy, mesna failed to reduce tHcy to normal levels. The cumulative effects of mesna administration over a longer treatment period should be evaluated. Official Title ----------------- The Effects of 12 mg/kg Intravenous Mesna on Plasma Total Homocysteine Concentration in Patients With End-stage Renal Disease Requiring Hemodialysis Conditions ----------------- End Stage Renal Disease Intervention / Treatment ----------------- * Drug: Mesna * Other: Saline Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients with end-stage renal disease who have received hemodialysis thrice weekly for at least 90 days Serum albumin > 30 g/L. Exclusion Criteria: Patients who refuse to sign a letter of informed consent Women who are or are trying to become pregnant or are breast-feeding. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: Placebo<br>Saline IV infusion over five minutes at the beginning of dialysis. | Other: Saline<br>* Saline IV infusion over five minutes at the beginning of dialysis thrice weekly.<br>| | Active Comparator: Mesna<br>12 mg/kg mesna IV infusion over five minutes at the beginning of dialysis. | Drug: Mesna<br>* 12 mg/kg IV infusion over five minutes at the beginning of dialysis thrice weekly.<br>* Other names: Uromitexan;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Difference in plasma total homocysteine between placebo and mesna treatments | | Four weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Excretion of mesna during hemodialysis | | duration of dialytic session | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- homocysteine, hemodialysis, mesna

NCT01304628

Cross-Over Study of Subcutaneous Study Drug for the Treatment of Patients With Mild to Moderate Asthma

The objective of this study is to evaluate if single subcutaneous (SC) doses of PL-3994, administered to patients with asthma can achieve a clinically meaningful increase in pulmonary function (Forced Expiratory Volume in one second: FEV1) while maintaining an acceptable safety profile. The study will characterize the bronchodilator effect, dose and safety of PL-3994 in a population of moderately severe, stable asthmatics following overnight withdrawal of beta-2 agonists.

A Phase 2a, Double-Blinded, Multi-Center, Escalating Dose Group, Placebo Controlled, Cross-Over Study to Evaluate the Safety, Efficacy and Tolerability of Subcutaneously Administered PL-3994 for the Treatment of Patients With Mild to Moderate Asthma

Asthma

* Drug: PL-3994

Inclusion Criteria:~Subject has provided written informed consent~The subject is male or female >18 to 65 years of age~Patient has a clinical history of asthma as defined by the National Asthma Education and Prevention Program.~Documented bronchodilator response to albuterol as defined by the American Thoracic Society (> 200 mL and > 12% increase in FEV1 after bronchodilator inhalation)~FEV1 post-bronchodilator of between 55% and 80% predicted.~Currently taking 200-1000 mcg (fluticasone equivalent) of inhaled corticosteroids~All inclusion criteria met within the past 12 months.~If the subject or subject's partner is of child-bearing potential, a medically acceptable form of contraception will be used for three months prior to the screening visit (females only), for the duration of the study and for one month following the last dose of the study drug. Medically acceptable contraceptives include: (1) surgical sterilization, (2) FDA-approved female hormonal contraceptives, (3) an intrauterine device (IUD), (4) condoms with spermicide, or (5) diaphragm with spermicide.~If the subject had a vasectomy greater than 6 months prior to the screen visit, this will also be acceptable.~Exclusion Criteria:~Current diagnosis, as per subject or investigator or screening assessment, of:~unstable or uncontrolled disease in any organ system (including cardiovascular) on present therapy~psychiatric disease requiring daily medication, including controlled or uncontrolled schizophrenia or any other uncontrolled psychiatric condition~significant neurological disease~current or history of any cancer (except non-melanomatous skin cancer) diagnosed less than 5 years prior to screening~acute or chronic disease requiring frequent changes in medications or changes in dosages of chronic therapy~history of alcohol abuse within the past 5 years~positive result for the alcohol and/or drug tests at screening or check-in~positive for HIV, or Hep B&C at screening~blood donation within 30 days of screening or plasma donation within 7 days of screening~weight > 100 kg or < 50 kg~clinically significant electrocardiogram (ECG) at screening~any clinically significant (per the investigator) lab abnormalities~any fever or other clinically significant physical exam abnormalities~History of COPD or any other lung disease~Greater than 10 packs per year smoking history and any cigarette smoking within the past 12 months~Patients unable to withhold bronchodilator treatment for 12 hours prior to dosing~Patients with hypoxia at screen or Check -in Visit 2, Day 1 or Visit 3, Day 7 (oxygen saturation measured by pulse oximetry [SpO2] < 90%)~Tachycardia (heart rate > 100 beats/min) at screening~Currently being treated for Hypertension or taking any other medications that affect blood pressure significantly.~Currently taking any medications that inhibit PDE activity or which affect the cyclic guanisine mono-phosphate (cGMP) pathway (e.g. theophylline). These medications will be prohibited during the study and for at least 5 half- lives prior to Check-in Visit 2, Day 1 or Visit 3, Day 7 so that cGMP measurements will not be affected.~Hypotension (systolic blood pressure < 110 mmHg) at Screening or Check-in Visit 2, Day 1 or Visit 3, Day 7~Chronic kidney disease defined as estimated glomerular filtration rate (eGFR) <50 mL/m2.~Diagnosis of heart failure or history of hospitalization for congestive heart failure.~History of coronary artery disease defined as prior myocardial infarction, prior revascularization procedure, or >50% coronary artery obstruction by angiography.~Prior history of stroke or transient ischemic attack.~Female patients of childbearing potential who are nursing or have a positive pregnancy test at Screening or Check -in Visit 2, Day 1 or Visit 3, Day 7~Any major disability or disease with expected survival less than 6 months~Administration of any investigational drug or implantation of investigational device, or participation in another trial, within 30 days of screening.~Inability to perform acceptable, quality serial spirometry

18 Years

65 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Forced Expiratory Volume in one second (FEV1) | Serial spirometry measures, including FEV1, assessed at specified time periods over 12 hours post dose. | Throughout 12 hours post dosing |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Forced Vital Capacity (FVC) | Serial spirometry measures, including FVC, assessed at specified time periods over 12 hours post dose. | Throughout 12 hours post dosing |

asthma

Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive, Lung Diseases, Respiratory Hypersensitivity, Hypersensitivity, Immediate, Hypersensitivity, Immune System Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: PL-3994 (4 escalating doses)<br> | Drug: PL-3994<br>* subcutaneous PL-3994, single dose, 4 escalating dose groups<br>| | Placebo Comparator: Placebo<br> | Drug: PL-3994<br>* subcutaneous PL-3994, single dose, 4 escalating dose groups<br>|

Cross-Over Study of Subcutaneous Study Drug for the Treatment of Patients With Mild to Moderate Asthma Study Overview ================= Brief Summary ----------------- The objective of this study is to evaluate if single subcutaneous (SC) doses of PL-3994, administered to patients with asthma can achieve a clinically meaningful increase in pulmonary function (Forced Expiratory Volume in one second: FEV1) while maintaining an acceptable safety profile. The study will characterize the bronchodilator effect, dose and safety of PL-3994 in a population of moderately severe, stable asthmatics following overnight withdrawal of beta-2 agonists. Official Title ----------------- A Phase 2a, Double-Blinded, Multi-Center, Escalating Dose Group, Placebo Controlled, Cross-Over Study to Evaluate the Safety, Efficacy and Tolerability of Subcutaneously Administered PL-3994 for the Treatment of Patients With Mild to Moderate Asthma Conditions ----------------- Asthma Intervention / Treatment ----------------- * Drug: PL-3994 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Subject has provided written informed consent The subject is male or female >18 to 65 years of age Patient has a clinical history of asthma as defined by the National Asthma Education and Prevention Program. Documented bronchodilator response to albuterol as defined by the American Thoracic Society (> 200 mL and > 12% increase in FEV1 after bronchodilator inhalation) FEV1 post-bronchodilator of between 55% and 80% predicted. Currently taking 200-1000 mcg (fluticasone equivalent) of inhaled corticosteroids All inclusion criteria met within the past 12 months. If the subject or subject's partner is of child-bearing potential, a medically acceptable form of contraception will be used for three months prior to the screening visit (females only), for the duration of the study and for one month following the last dose of the study drug. Medically acceptable contraceptives include: (1) surgical sterilization, (2) FDA-approved female hormonal contraceptives, (3) an intrauterine device (IUD), (4) condoms with spermicide, or (5) diaphragm with spermicide. If the subject had a vasectomy greater than 6 months prior to the screen visit, this will also be acceptable. Exclusion Criteria: Current diagnosis, as per subject or investigator or screening assessment, of: unstable or uncontrolled disease in any organ system (including cardiovascular) on present therapy psychiatric disease requiring daily medication, including controlled or uncontrolled schizophrenia or any other uncontrolled psychiatric condition significant neurological disease current or history of any cancer (except non-melanomatous skin cancer) diagnosed less than 5 years prior to screening acute or chronic disease requiring frequent changes in medications or changes in dosages of chronic therapy history of alcohol abuse within the past 5 years positive result for the alcohol and/or drug tests at screening or check-in positive for HIV, or Hep B&C at screening blood donation within 30 days of screening or plasma donation within 7 days of screening weight > 100 kg or < 50 kg clinically significant electrocardiogram (ECG) at screening any clinically significant (per the investigator) lab abnormalities any fever or other clinically significant physical exam abnormalities History of COPD or any other lung disease Greater than 10 packs per year smoking history and any cigarette smoking within the past 12 months Patients unable to withhold bronchodilator treatment for 12 hours prior to dosing Patients with hypoxia at screen or Check -in Visit 2, Day 1 or Visit 3, Day 7 (oxygen saturation measured by pulse oximetry [SpO2] < 90%) Tachycardia (heart rate > 100 beats/min) at screening Currently being treated for Hypertension or taking any other medications that affect blood pressure significantly. Currently taking any medications that inhibit PDE activity or which affect the cyclic guanisine mono-phosphate (cGMP) pathway (e.g. theophylline). These medications will be prohibited during the study and for at least 5 half- lives prior to Check-in Visit 2, Day 1 or Visit 3, Day 7 so that cGMP measurements will not be affected. Hypotension (systolic blood pressure < 110 mmHg) at Screening or Check-in Visit 2, Day 1 or Visit 3, Day 7 Chronic kidney disease defined as estimated glomerular filtration rate (eGFR) <50 mL/m2. Diagnosis of heart failure or history of hospitalization for congestive heart failure. History of coronary artery disease defined as prior myocardial infarction, prior revascularization procedure, or >50% coronary artery obstruction by angiography. Prior history of stroke or transient ischemic attack. Female patients of childbearing potential who are nursing or have a positive pregnancy test at Screening or Check -in Visit 2, Day 1 or Visit 3, Day 7 Any major disability or disease with expected survival less than 6 months Administration of any investigational drug or implantation of investigational device, or participation in another trial, within 30 days of screening. Inability to perform acceptable, quality serial spirometry Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: PL-3994 (4 escalating doses)<br> | Drug: PL-3994<br>* subcutaneous PL-3994, single dose, 4 escalating dose groups<br>| | Placebo Comparator: Placebo<br> | Drug: PL-3994<br>* subcutaneous PL-3994, single dose, 4 escalating dose groups<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Forced Expiratory Volume in one second (FEV1) | Serial spirometry measures, including FEV1, assessed at specified time periods over 12 hours post dose. | Throughout 12 hours post dosing | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Forced Vital Capacity (FVC) | Serial spirometry measures, including FVC, assessed at specified time periods over 12 hours post dose. | Throughout 12 hours post dosing | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- asthma

NCT00469573

Safety and Efficacy of Optive in Contact Lens Wearers With Dry Eyes

The purpose of this study is to determine if Optive®eye drops are safe for people who wear contact lenses and have dry eyes. The second goal of the study is to determine if using Optive®eye drops can improve my dry eye scores on a standard dry eye test (called the OSDI).

Safety and Efficacy of Optive in Contact Lens Wearers With Dry Eyes

Dry Eye

* Drug: 1. Optive

Inclusion Criteria:~Men and women 18 and over~Self-reported use of daily-wear soft contact lenses that have been a proper fit for at least one month prior to the screening visit.~Complaint of dry eyes~OSDI score > 23~Exclusion Criteria:~Use of RGP or PMMA contact lenses~Poorly fitting contact lenses~Concurrent ocular conditions or pathology that could affect contact lens fit or patient's ability to complete study~Concurrent use of topical medications other than study medications~Use of systemic medications with ocular drying sequelae:~Antihistamines~Decongestants~Antispasmotics Antidepressants Change in contact lens care solutions within the prior 30 days

18 Years

All

Accepts Healthy Volunteers

Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Safety | | 8 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Efficacy | | 8 months |

Dry Eye Syndromes, Keratoconjunctivitis Sicca, Lacrimal Apparatus Diseases, Eye Diseases, Keratoconjunctivitis, Conjunctivitis, Conjunctival Diseases, Keratitis, Corneal Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: 1.<br> | Drug: 1. Optive<br>* Optive 15ml- (in the eye) Instill one drop twice daily in each eye<br>|

Safety and Efficacy of Optive in Contact Lens Wearers With Dry Eyes Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine if Optive®eye drops are safe for people who wear contact lenses and have dry eyes. The second goal of the study is to determine if using Optive®eye drops can improve my dry eye scores on a standard dry eye test (called the OSDI). Official Title ----------------- Safety and Efficacy of Optive in Contact Lens Wearers With Dry Eyes Conditions ----------------- Dry Eye Intervention / Treatment ----------------- * Drug: 1. Optive Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Men and women 18 and over Self-reported use of daily-wear soft contact lenses that have been a proper fit for at least one month prior to the screening visit. Complaint of dry eyes OSDI score > 23 Exclusion Criteria: Use of RGP or PMMA contact lenses Poorly fitting contact lenses Concurrent ocular conditions or pathology that could affect contact lens fit or patient's ability to complete study Concurrent use of topical medications other than study medications Use of systemic medications with ocular drying sequelae: Antihistamines Decongestants Antispasmotics Antidepressants Change in contact lens care solutions within the prior 30 days Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: 1.<br> | Drug: 1. Optive<br>* Optive 15ml- (in the eye) Instill one drop twice daily in each eye<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Safety | | 8 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Efficacy | | 8 months |

NCT03374800

Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial

Patients who are critically ill in the in the Intensive Care Unit (ICU), especially those who need a breathing machine, can develop ulcers in the stomach that bleed. To prevent bleeding, many such patients around the world receive a drug called pantoprazole that decreases acid production. However, today, compared to decades ago, critically ill patients rarely develop gastrointestinal bleeding. This decrease is likely due to modern medicine, better resuscitation and earlier feeding. There may also be harms associated with pantoprazole and other drugs that reduce acid levels in the stomach including lung infections (pneumonia) and bowel infections (clostridium difficile). Studies in this area are old and of modest quality. Therefore, it is difficult to know whether pantoprazole does decrease stomach bleeding these days, or whether the possible harms of lung and bowel infections are actually more common and more serious problems. The goal of this international study is to determine if, in critically ill patients using breathing machines, the use of pantoprazole is effective in preventing bleeding from stomach ulcers or whether it causes more problems such as lung infection (pneumonia) and bowel infection (Clostridium difficile), or whether pantoprazole has no effect at all. Whether the harms are worth the benefits, and whether the benefits are worth the costs, will be determined by an economic analysis to inform patients, families, clinicians, and healthcare systems globally.

Background: For 40 years, pharmacologic prevention of stress ulcer-related gastrointestinal (GI) bleeding with acid suppression has been the standard of care for mechanically ventilated ICU patients. Worldwide, proton pump inhibitors (PPIs) are more commonly used than histamine-2-receptor antagonists. Observational studies and the latest network meta-analysis suggest that PPIs increase the risk of ventilator-associated pneumonia (VAP) and Clostridioides difficile infection (CDI). However, a recent large randomized trial showed that pantoprazole had no impact on the primary outcome of 90-day mortality. The secondary outcome (a composite of pneumonia, gastrointestinal bleeding, CDI and acute myocardial ischemia) was not different between the groups. Although pantoprazole was associated with a significantly lower rate of GI bleeding, some bleeding events required no blood transfusion, endoscopy or other diagnostic or therapeutic interventions, calling into question whether these bleeds were truly patient-important. Further, patients with high illness severity on pantoprazole had a significant, unexplainable higher risk of death than those receiving placebo.~REVISE Pilot Trial: We completed the 91-patient REVISE Pilot Trial in Canada, Australia and Saudi Arabia, demonstrating a high consent rate (77.8%); recruitment rate (2.6 patients/month/center); and protocol adherence (96.8%), thereby successfully establishing the feasibility of a larger REVISE Trial.~Objectives of the REVISE Trial: To determine, among mechanically ventilated patients, the effect of pantoprazole versus placebo on the primary efficacy outcome of clinically important upper GI bleeding, and the primary safety outcome of 90-day mortality. Secondary outcomes are VAP, CDI, acute kidney injury, hospital mortality and patient-important GI bleeding. Tertiary outcomes are transfused packed red blood cells, serum creatinine, duration of mechanical ventilation, duration of ICU stay and duration of hospital stay.~Methods: We will include 4,800 ICU patients >18 years old who have an anticipated duration of mechanical ventilation of ≥48 hours. Exclusion criteria are acute or recent GI bleeding, dual antiplatelet therapy, combined antiplatelet and anticoagulant therapy, hopeless prognosis or intent to withdraw advanced life support, and previous enrolment in this or a confounding trial. Patients will be randomized in a fixed 1:1 allocation, stratified by center and pre-ICU acid suppression ('start or no start' strata, and 'continue or discontinue' strata). Research Coordinators will obtain informed consent using a deferred or a priori consent model. Study Pharmacists will obtain concealed allocation from the REVISE website; all research team and clinical team members, patients and families will be blinded. Patients will receive pantoprazole 40 mg or identical placebo intravenously daily while in ICU up to 90 days or until: 1) successful discontinuation of mechanical ventilation for >48 hours; 2) development of clinically important GI bleeding, or 3) death in ICU. Analyses will be by intention-to-treat and per protocol.~Collaborations: REVISE will be conducted in collaboration with the Canadian Critical Care Trials Group, the Australian and New Zealand Critical Care Trials Group, other consortia and interested investigators, under the auspices of the International Forum for Acute Care Trialists.~Ethical Imperative: Many factors converge to underscore the ethical imperative for REVISE. Critical care has evolved, research standards have improved, epidemiology may have changed, the risk:benefit and cost:benefit ratios of prophylaxis may have shifted. Thus, stress ulcer prophylaxis may need to be REVISED.~Relevance: Most mechanically ventilated patients around the world receive daily stress ulcer prophylaxis, although variation exists such that some centers do not use any. Many RCTs of stress ulcer prophylaxis were conducted 10-30 years ago, several are at moderate or high risk of bias, and cointerventions may not reflect current critical care. A recent large trial raised concerns about death associated with pantoprazole in the most severely ill patient subgroup. Although GI bleeding events were less frequent, they may not have been patient-important, and there were no other benefits observed. Consensus in the scientific and clinical community is that equipoise remains regarding whether routine use of pantoprazole should continue for stress ulcer prophylaxis during critical illness. The question is especially important for patients who are receiving acid suppression pre-ICU, those who are receiving enteral nutrition, and those at high risk of death. Today, infectious complications of PPIs have emerged as potentially more common and serious than upper GI bleeding. The number needed to prophylax to prevent 1 GI bleed and the cost per GI bleed averted may be very high; furthermore, the number needed to harm to cause 1 episode of VAP or CDI may be low. Recent practice guidelines are conflicting. Remaining doubts about the effectiveness and safety of PPIs urge re-examination of universal prophylaxis for possible de-adoption. Aligned with the 'Choosing Wisely' Campaign, REVISE and the companion economic evaluation (E-REVISE) will be incorporated into guidelines to inform global practice.

Re-EValuating the Inhibition of Stress Erosions: Prophylaxis Against Gastrointestinal Bleeding in the Critically Ill (The REVISE) Trial

Gastrointestinal Hemorrhage (Clinically Important, Upper)

* Drug: Placebo (0.9% saline) * Drug: Pantoprazole

Inclusion Criteria:~Age 18 years or more.~Receiving invasive mechanical ventilation in an ICU and in the opinion of the treating ICU physician mechanical ventilation will not be discontinued before the end of the day after tomorrow.~Exclusion Criteria:~The treating clinician considers either Pantoprazole or placebo are indicated or contraindicated for this patient.~Pantoprazole contraindicated for patient due to local product information;~Australia/New Zealand;~being treated with HIV protease inhibitors atazanavir or nelfinavir~being treated with high dose methotrexate (i.e., greater than 300 mg as part of a chemotherapy regimen).~documented cirrhosis or severe liver disease (for example as indicated by an INR greater than 5.0 due to underlying liver disease).~Canada;~being treated with rilpivirine or atazanavir~patients who are hypersensitive to pantoprazole, substituted benzimidazoles, or to any ingredient in the formulation~Patients in whom a PPI or histamine 2 receptor antagonist (H2RA) is indicated due to active bleeding or increased bleeding risk, defined as patients with acute GI bleeding, severe oesophagitis or peptic ulcer disease within the previous 8 weeks, Zollinger Ellison syndrome, Barrett's oesophagus or any previous admission to hospital because of upper GI bleeding (patients receiving PPIs for mild dyspepsia or mild gastroesophageal reflux disease or an uncertain indication are not excluded).~Received invasive mechanical ventilation during this ICU admission for 72 hours or more.~Patients who have received more than 24 hours treatment (i.e., more than one daily dose equivalent) with a PPI or H2RA during this ICU admission.~Being treated with or need for dual anti-platelet therapy.~Admitted for palliative care or the ICU physician is not committed to continuing life-sustaining therapies at the time of enrolment.~Known or suspected pregnancy.~Physician, patient, or substitute decision maker (SDM) declines.~Previously enrolled in the REVISE trial~Enrolled in another trial for which co-enrolment is not approved.

18 Years

All

No

Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: A prospective, international, multicentre, parallel group, concealed, blinded, randomized trial in critically ill mechanically ventilated adults Masking: Quadruple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Rate of clinically important gastro-intestinal bleeding | Clinically important GI bleeding requires the presence of overt GI bleeding which is defined as one of the following;~Hematemesis~Overt nasogastric bleeding~Melena~Hematochezia~PLUS (in the absence of another cause), at least one of the following in the 24 hours following overt GI bleeding:~Haemodynamic change defined as a spontaneous decrease in invasively monitored mean arterial pressure or non-invasive systolic or diastolic blood pressure of 20 mmHg or more or an orthostatic increase in pulse rate of 20 beats/minute and a decrease in systolic blood pressure of 10 mmHg, with or without vasopressor initiation, or increase~Vasopressor initiation~A decrease in haemoglobin of ≥ 20 g/l in a 24-hour period or less,~Transfusion of ≥2 units of packed red blood cells within 24 hours of bleeding to maintain stable haemoglobin or haemodynamics, or~Need for therapeutic intervention (e.g. angiography, surgery or endoscopic treatment of bleeding). | 90 days (In ICU or resulting in ICU readmission, censored at 90 days after randomization) | | Primary Safety Outcome: 90 Day Mortality | Mortality status at day 90 post randomization | 90 days post randomization |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Rate of ventilator associated pneumonia (VAP) in ICU | Diagnostic criteria for VAP include: previous mechanical ventilation for at least 48 hours, a new, progressive or persistent radiographic infiltrate on chest X-ray (without other obvious cause) plus at least 2 of the following 4 features:~fever or hypothermia (temperature >38 °C or <36 °C)~relative leukopenia or leukocytosis (WBC<4.0 or >12 x 10^9/L)~purulent sputum~gas exchange deterioration | 90 Days (while in ICU,censored at 90 days after randomization) | | Rate of clostridium difficile associated infection | We will use clinical features (diarrhea, ileus, toxic megacolon) and either microbiological evidence of toxin producing Clostridium difficile or Pseudomembranous colitis on colonoscopy. | 90 days (during the index hospital admission, censored at 90 days) | | New initiation of treatment with renal replacement therapy in ICU | Rate of New initiation of treatment with renal replacement therapy in ICU | 90 Days (In the ICU, censored at 90 days) | | Rate of all-cause-in-hospital mortality | hospital mortality | While in hospital, censored at 90 days after randomization | | Rate of patient important GI bleeding in ICU or resulting in ICU readmission, censored at 90 days after randomization | Patient important GI bleeding in ICU or resulting in ICU readmission, censored at 90 days after randomization | Censored at 90 days after randomization |

Pantoprazole, Anti-Ulcer Agents, Gastrointestinal Agents, Proton Pump Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: Placebo (0.9% saline)<br>Withholding Stress ulcer prophylaxis (intravenous 0.9% saline as placebo) | Drug: Placebo (0.9% saline)<br>* normal saline<br>* Other names: normal saline; NaCl 0.9%;| | Active Comparator: Stress Ulcer Prophylaxis (Pantoprazole)<br>pantoprazole 40mg powder for injection reconstituted with 0.9% saline | Drug: Pantoprazole<br>* 40 mg powder for injection reconstituted with 0.9% saline<br>* Other names: Protonix;|

Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial Study Overview ================= Brief Summary ----------------- Patients who are critically ill in the in the Intensive Care Unit (ICU), especially those who need a breathing machine, can develop ulcers in the stomach that bleed. To prevent bleeding, many such patients around the world receive a drug called pantoprazole that decreases acid production. However, today, compared to decades ago, critically ill patients rarely develop gastrointestinal bleeding. This decrease is likely due to modern medicine, better resuscitation and earlier feeding. There may also be harms associated with pantoprazole and other drugs that reduce acid levels in the stomach including lung infections (pneumonia) and bowel infections (clostridium difficile). Studies in this area are old and of modest quality. Therefore, it is difficult to know whether pantoprazole does decrease stomach bleeding these days, or whether the possible harms of lung and bowel infections are actually more common and more serious problems. The goal of this international study is to determine if, in critically ill patients using breathing machines, the use of pantoprazole is effective in preventing bleeding from stomach ulcers or whether it causes more problems such as lung infection (pneumonia) and bowel infection (Clostridium difficile), or whether pantoprazole has no effect at all. Whether the harms are worth the benefits, and whether the benefits are worth the costs, will be determined by an economic analysis to inform patients, families, clinicians, and healthcare systems globally. Detailed Description ----------------- Background: For 40 years, pharmacologic prevention of stress ulcer-related gastrointestinal (GI) bleeding with acid suppression has been the standard of care for mechanically ventilated ICU patients. Worldwide, proton pump inhibitors (PPIs) are more commonly used than histamine-2-receptor antagonists. Observational studies and the latest network meta-analysis suggest that PPIs increase the risk of ventilator-associated pneumonia (VAP) and Clostridioides difficile infection (CDI). However, a recent large randomized trial showed that pantoprazole had no impact on the primary outcome of 90-day mortality. The secondary outcome (a composite of pneumonia, gastrointestinal bleeding, CDI and acute myocardial ischemia) was not different between the groups. Although pantoprazole was associated with a significantly lower rate of GI bleeding, some bleeding events required no blood transfusion, endoscopy or other diagnostic or therapeutic interventions, calling into question whether these bleeds were truly patient-important. Further, patients with high illness severity on pantoprazole had a significant, unexplainable higher risk of death than those receiving placebo. REVISE Pilot Trial: We completed the 91-patient REVISE Pilot Trial in Canada, Australia and Saudi Arabia, demonstrating a high consent rate (77.8%); recruitment rate (2.6 patients/month/center); and protocol adherence (96.8%), thereby successfully establishing the feasibility of a larger REVISE Trial. Objectives of the REVISE Trial: To determine, among mechanically ventilated patients, the effect of pantoprazole versus placebo on the primary efficacy outcome of clinically important upper GI bleeding, and the primary safety outcome of 90-day mortality. Secondary outcomes are VAP, CDI, acute kidney injury, hospital mortality and patient-important GI bleeding. Tertiary outcomes are transfused packed red blood cells, serum creatinine, duration of mechanical ventilation, duration of ICU stay and duration of hospital stay. Methods: We will include 4,800 ICU patients >18 years old who have an anticipated duration of mechanical ventilation of ≥48 hours. Exclusion criteria are acute or recent GI bleeding, dual antiplatelet therapy, combined antiplatelet and anticoagulant therapy, hopeless prognosis or intent to withdraw advanced life support, and previous enrolment in this or a confounding trial. Patients will be randomized in a fixed 1:1 allocation, stratified by center and pre-ICU acid suppression ('start or no start' strata, and 'continue or discontinue' strata). Research Coordinators will obtain informed consent using a deferred or a priori consent model. Study Pharmacists will obtain concealed allocation from the REVISE website; all research team and clinical team members, patients and families will be blinded. Patients will receive pantoprazole 40 mg or identical placebo intravenously daily while in ICU up to 90 days or until: 1) successful discontinuation of mechanical ventilation for >48 hours; 2) development of clinically important GI bleeding, or 3) death in ICU. Analyses will be by intention-to-treat and per protocol. Collaborations: REVISE will be conducted in collaboration with the Canadian Critical Care Trials Group, the Australian and New Zealand Critical Care Trials Group, other consortia and interested investigators, under the auspices of the International Forum for Acute Care Trialists. Ethical Imperative: Many factors converge to underscore the ethical imperative for REVISE. Critical care has evolved, research standards have improved, epidemiology may have changed, the risk:benefit and cost:benefit ratios of prophylaxis may have shifted. Thus, stress ulcer prophylaxis may need to be REVISED. Relevance: Most mechanically ventilated patients around the world receive daily stress ulcer prophylaxis, although variation exists such that some centers do not use any. Many RCTs of stress ulcer prophylaxis were conducted 10-30 years ago, several are at moderate or high risk of bias, and cointerventions may not reflect current critical care. A recent large trial raised concerns about death associated with pantoprazole in the most severely ill patient subgroup. Although GI bleeding events were less frequent, they may not have been patient-important, and there were no other benefits observed. Consensus in the scientific and clinical community is that equipoise remains regarding whether routine use of pantoprazole should continue for stress ulcer prophylaxis during critical illness. The question is especially important for patients who are receiving acid suppression pre-ICU, those who are receiving enteral nutrition, and those at high risk of death. Today, infectious complications of PPIs have emerged as potentially more common and serious than upper GI bleeding. The number needed to prophylax to prevent 1 GI bleed and the cost per GI bleed averted may be very high; furthermore, the number needed to harm to cause 1 episode of VAP or CDI may be low. Recent practice guidelines are conflicting. Remaining doubts about the effectiveness and safety of PPIs urge re-examination of universal prophylaxis for possible de-adoption. Aligned with the 'Choosing Wisely' Campaign, REVISE and the companion economic evaluation (E-REVISE) will be incorporated into guidelines to inform global practice. Official Title ----------------- Re-EValuating the Inhibition of Stress Erosions: Prophylaxis Against Gastrointestinal Bleeding in the Critically Ill (The REVISE) Trial Conditions ----------------- Gastrointestinal Hemorrhage (Clinically Important, Upper) Intervention / Treatment ----------------- * Drug: Placebo (0.9% saline) * Drug: Pantoprazole Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 18 years or more. Receiving invasive mechanical ventilation in an ICU and in the opinion of the treating ICU physician mechanical ventilation will not be discontinued before the end of the day after tomorrow. Exclusion Criteria: The treating clinician considers either Pantoprazole or placebo are indicated or contraindicated for this patient. Pantoprazole contraindicated for patient due to local product information; Australia/New Zealand; being treated with HIV protease inhibitors atazanavir or nelfinavir being treated with high dose methotrexate (i.e., greater than 300 mg as part of a chemotherapy regimen). documented cirrhosis or severe liver disease (for example as indicated by an INR greater than 5.0 due to underlying liver disease). Canada; being treated with rilpivirine or atazanavir patients who are hypersensitive to pantoprazole, substituted benzimidazoles, or to any ingredient in the formulation Patients in whom a PPI or histamine 2 receptor antagonist (H2RA) is indicated due to active bleeding or increased bleeding risk, defined as patients with acute GI bleeding, severe oesophagitis or peptic ulcer disease within the previous 8 weeks, Zollinger Ellison syndrome, Barrett's oesophagus or any previous admission to hospital because of upper GI bleeding (patients receiving PPIs for mild dyspepsia or mild gastroesophageal reflux disease or an uncertain indication are not excluded). Received invasive mechanical ventilation during this ICU admission for 72 hours or more. Patients who have received more than 24 hours treatment (i.e., more than one daily dose equivalent) with a PPI or H2RA during this ICU admission. Being treated with or need for dual anti-platelet therapy. Admitted for palliative care or the ICU physician is not committed to continuing life-sustaining therapies at the time of enrolment. Known or suspected pregnancy. Physician, patient, or substitute decision maker (SDM) declines. Previously enrolled in the REVISE trial Enrolled in another trial for which co-enrolment is not approved. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: A prospective, international, multicentre, parallel group, concealed, blinded, randomized trial in critically ill mechanically ventilated adults Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: Placebo (0.9% saline)<br>Withholding Stress ulcer prophylaxis (intravenous 0.9% saline as placebo) | Drug: Placebo (0.9% saline)<br>* normal saline<br>* Other names: normal saline; NaCl 0.9%;| | Active Comparator: Stress Ulcer Prophylaxis (Pantoprazole)<br>pantoprazole 40mg powder for injection reconstituted with 0.9% saline | Drug: Pantoprazole<br>* 40 mg powder for injection reconstituted with 0.9% saline<br>* Other names: Protonix;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Rate of clinically important gastro-intestinal bleeding | Clinically important GI bleeding requires the presence of overt GI bleeding which is defined as one of the following; Hematemesis Overt nasogastric bleeding Melena Hematochezia PLUS (in the absence of another cause), at least one of the following in the 24 hours following overt GI bleeding: Haemodynamic change defined as a spontaneous decrease in invasively monitored mean arterial pressure or non-invasive systolic or diastolic blood pressure of 20 mmHg or more or an orthostatic increase in pulse rate of 20 beats/minute and a decrease in systolic blood pressure of 10 mmHg, with or without vasopressor initiation, or increase Vasopressor initiation A decrease in haemoglobin of ≥ 20 g/l in a 24-hour period or less, Transfusion of ≥2 units of packed red blood cells within 24 hours of bleeding to maintain stable haemoglobin or haemodynamics, or Need for therapeutic intervention (e.g. angiography, surgery or endoscopic treatment of bleeding). | 90 days (In ICU or resulting in ICU readmission, censored at 90 days after randomization) | | Primary Safety Outcome: 90 Day Mortality | Mortality status at day 90 post randomization | 90 days post randomization | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Rate of ventilator associated pneumonia (VAP) in ICU | Diagnostic criteria for VAP include: previous mechanical ventilation for at least 48 hours, a new, progressive or persistent radiographic infiltrate on chest X-ray (without other obvious cause) plus at least 2 of the following 4 features: fever or hypothermia (temperature >38 °C or <36 °C) relative leukopenia or leukocytosis (WBC<4.0 or >12 x 10^9/L) purulent sputum gas exchange deterioration | 90 Days (while in ICU,censored at 90 days after randomization) | | Rate of clostridium difficile associated infection | We will use clinical features (diarrhea, ileus, toxic megacolon) and either microbiological evidence of toxin producing Clostridium difficile or Pseudomembranous colitis on colonoscopy. | 90 days (during the index hospital admission, censored at 90 days) | | New initiation of treatment with renal replacement therapy in ICU | Rate of New initiation of treatment with renal replacement therapy in ICU | 90 Days (In the ICU, censored at 90 days) | | Rate of all-cause-in-hospital mortality | hospital mortality | While in hospital, censored at 90 days after randomization | | Rate of patient important GI bleeding in ICU or resulting in ICU readmission, censored at 90 days after randomization | Patient important GI bleeding in ICU or resulting in ICU readmission, censored at 90 days after randomization | Censored at 90 days after randomization |

NCT00120471

Safety and Blood Levels of Tenofovir Disoproxil Fumarate in HIV Infected Pregnant Women and Their Babies

To prevent mother-to-child transmission (MTCT) of HIV in resource-limited countries, a simple yet effective treatment plan is needed. Tenofovir disoproxil fumarate (TDF) is an anti-HIV drug approved for use in the United States for the treatment of HIV infected adults. The purpose of this study is to determine the safety, tolerability, and blood levels of TDF in HIV infected pregnant women and their babies. The study will be conducted at sites in Malawi and Brazil.

Rates of MTCT of HIV have dramatically decreased in resource-rich countries since the introduction of antiretroviral (ARV) prophylaxis; increased prenatal care, HIV testing, and counseling; elective cesarean delivery; and avoidance of breastfeeding. In resource-limited countries, however, MTCT of HIV continues to be a widespread problem. In these parts of the world, ARV prophylaxis is too expensive and too difficult to adequately administer; mothers often do not receive proper prenatal care; cesarean delivery may pose risks to the mother and and her infant; and due to the lack of safe, affordable, and socially acceptable alternatives, HIV infected mothers breastfeed their infants. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of TDF in HIV infected pregnant women and their infants.~Participants in this study will be enrolled through 12 months after delivery. During the last trimester of pregnancy, HIV infected women will be screened for eligibility. Women will be enrolled into the study upon presentation at the study site for delivery. Standard of care with ARVs for prevention of MTCT will be offered to all women and their infants both inside and outside of the study; however, such ARVs will not be provided by this study.~There will be four cohorts in this study:~Cohort 1 women will receive a single dose of TDF (SD TDF) during active labor. Cohort 1 women will be hospitalized at the delivery facility through Day 3 postpartum.~Cohort 2 women will not receive any TDF. Cohort 2 women will be hospitalized at the delivery facility through Day 7 postpartum. Their infants will receive TDF at birth and on Days 3 and 5 after birth.~Cohort 3 will not begin enrolling women until data safety evaluations of Cohorts 1 and 2 are completed. Cohort 3 women will be hospitalized at the delivery facility through Day 7 postpartum. Women in Cohort 3 will receive SD TDF during active labor, and their infants will receive TDF at birth and on Days 3 and 5 after birth.~Cohort 4, which was added to the study based on a review of data from the other cohorts, will be similar to Cohort 3, except that infants will receive daily TDF for the 7 days after birth. Researchers believe this higher and more frequent dosing of TDF in infants will help them meet the target TDF concentration specified in the protocol.~There will be seven study visits for women at study entry (Day 0), Day 2, between Days 5 and 7, at Weeks 6 and 12, and at Months 6 and 12 postpartum. Medical history, a short physical exam, and blood collection will occur at all visits. In Cohorts 1, 3, and 4, blood collection for PK studies will occur prior to receiving TDF and seven times post-dose.~There will be eight study visits for infants, which will occur within 24 hours of birth; on Day 3; between Days 5 and 7; at Weeks 6 and 12; and at Months 6, 9, and 12. Medical history, a physical exam, and blood collection will occur at all visits. Infants will have x-rays to assess bone health at Day 3 and Month 3, except in Cohort 4, which will not include x-rays of infants. Infants of Cohort 1 will have blood collection for PK studies at birth and four times after birth. Infants of Cohorts 2 and 3 will undergo blood collections for PK studies at birth, Day 3, and Day 5. Blood collection at these visits will occur before receiving TDF and 2 and 10 hours after receiving TDF. At birth, an additional collection will occur 18 to 24 hours after receiving TDF, and on Day 5, two additional collections will occur--at 18 to 24 hours and at 36 to 48 hours after receiving TDF. Infants of Cohort 4 will have blood collection for PK studies at birth and after their fourth and seventh doses of TDF.

A Phase I Open Label Trial of the Safety and Pharmacokinetics of Tenofovir Disoproxil Fumarate in HIV-1 Infected Pregnant Women and Their Infants

HIV Infections

* Drug: Tenofovir disoproxil fumarate * Drug: Tenofovir disoproxil fumarate * Drug: Tenofovir disoproxil fumarate

Inclusion Criteria for HIV Infected Pregnant Women:~HIV-1 infected~Intend to deliver at the study site~Willing to be contacted or visited at home~Willing to be admitted to and remain in the delivery facility through Day 3 postpartum (Cohort 1) or Day 7 postpartum (Cohorts 2 and 3)~Exclusion Criteria for HIV Infected Pregnant Women:~Prior treatment with TDF~Active opportunistic infection~Serious bacterial infection~Chronic malabsorption or diarrhea during the current pregnancy~Clinically significant disease or condition that, in the opinion of the study clinician, would interfere with the study~Known multiple gestation (twins, etc.) prior to study entry~Participation in any other therapeutic or vaccine trial during the current pregnancy~Use of certain medications~Any other condition or situation that, in the opinion of the investigator, would interfere with the study~For Cohort 4, use of atazanavir or lopinavir/ritonavir (Kaletra) within 2 weeks of anticipated delivery~Exclusion Criteria for Infants Born to HIV Infected Pregnant Women:~Birth weight of less than 2 kg (4.4 lbs)~Severe congenital malformation or other medical condition that may affect survival and, in the opinion of the clinician, participation in this study~Grade 2 or higher serum creatinine level or any other Grade 3 or higher toxicity~Part of a multiple birth (twins, etc.)

18 Years

All

No

Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Frequency of adverse events with a severity of Grade 3 or higher attributable to receipt of TDF | | Throughout study | | Maintenance of infant serum concentrations of TDF greater than 50 ng/ml | | Through Week 1 |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maternal HIV-1 RNA levels | | At study entry, Days 5 to 7, and Week 6 | | Viral resistance to TDF in all HIV-1 infected infants, all of the corresponding mothers (transmitters), and a subset of mothers whose infants are not infected (nontransmitters). Analysis of TDF in mothers may include testing of breastmilk samples. | | Throughout study | | HIV infection in infants | | Throughout study | | TDF concentration in amniotic fluid and breast milk | | Through Week 1 |

MTCT, Perinatal Transmission, HIV Seronegativity

Tenofovir, Antiviral Agents, Anti-Infective Agents, Reverse Transcriptase Inhibitors, Nucleic Acid Synthesis Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Anti-HIV Agents, Anti-Retroviral Agents

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: 1<br>Pregnant participants will receive a single dose of TDF during active labor. These participants will be hospitalized at the delivery facility through Day 3 postpartum. | Drug: Tenofovir disoproxil fumarate<br>* 600-mg tablet taken orally once daily<br>* Other names: TDF;| | Experimental: 2<br>Pregnant participants will not receive TDF. Participants will be hospitalized at the delivery facility through Day 7 postpartum. Their infants will receive TDF at birth and on Days 3 and 5 after birth. | Drug: Tenofovir disoproxil fumarate<br>* 4-mg/kg oral suspension taken at birth and on Days 3 and 5 after birth<br>* Other names: TDF;| | Experimental: 3<br>Pregnant participants will be hospitalized at the delivery facility through Day 7 postpartum. They will receive TDF during active labor and their infants will receive TDF at birth and on Days 3 and 5 after birth. | Drug: Tenofovir disoproxil fumarate<br>* 600-mg tablet taken orally once daily<br>* Other names: TDF;Drug: Tenofovir disoproxil fumarate<br>* 4-mg/kg oral suspension taken at birth and on Days 3 and 5 after birth<br>* Other names: TDF;| | Experimental: 4<br>Pregnant participants will be hospitalized at the delivery facility through Day 7 postpartum. Mothers will receive TDF during active labor and their infants will receive TDF at birth and daily for 7 days after birth. | Drug: Tenofovir disoproxil fumarate<br>* 600-mg tablet taken orally once daily<br>* Other names: TDF;Drug: Tenofovir disoproxil fumarate<br>* 6-mg/kg oral suspension taken at birth and daily for 7 days after birth<br>* Other names: TDF;|

Safety and Blood Levels of Tenofovir Disoproxil Fumarate in HIV Infected Pregnant Women and Their Babies Study Overview ================= Brief Summary ----------------- To prevent mother-to-child transmission (MTCT) of HIV in resource-limited countries, a simple yet effective treatment plan is needed. Tenofovir disoproxil fumarate (TDF) is an anti-HIV drug approved for use in the United States for the treatment of HIV infected adults. The purpose of this study is to determine the safety, tolerability, and blood levels of TDF in HIV infected pregnant women and their babies. The study will be conducted at sites in Malawi and Brazil. Detailed Description ----------------- Rates of MTCT of HIV have dramatically decreased in resource-rich countries since the introduction of antiretroviral (ARV) prophylaxis; increased prenatal care, HIV testing, and counseling; elective cesarean delivery; and avoidance of breastfeeding. In resource-limited countries, however, MTCT of HIV continues to be a widespread problem. In these parts of the world, ARV prophylaxis is too expensive and too difficult to adequately administer; mothers often do not receive proper prenatal care; cesarean delivery may pose risks to the mother and and her infant; and due to the lack of safe, affordable, and socially acceptable alternatives, HIV infected mothers breastfeed their infants. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of TDF in HIV infected pregnant women and their infants. Participants in this study will be enrolled through 12 months after delivery. During the last trimester of pregnancy, HIV infected women will be screened for eligibility. Women will be enrolled into the study upon presentation at the study site for delivery. Standard of care with ARVs for prevention of MTCT will be offered to all women and their infants both inside and outside of the study; however, such ARVs will not be provided by this study. There will be four cohorts in this study: Cohort 1 women will receive a single dose of TDF (SD TDF) during active labor. Cohort 1 women will be hospitalized at the delivery facility through Day 3 postpartum. Cohort 2 women will not receive any TDF. Cohort 2 women will be hospitalized at the delivery facility through Day 7 postpartum. Their infants will receive TDF at birth and on Days 3 and 5 after birth. Cohort 3 will not begin enrolling women until data safety evaluations of Cohorts 1 and 2 are completed. Cohort 3 women will be hospitalized at the delivery facility through Day 7 postpartum. Women in Cohort 3 will receive SD TDF during active labor, and their infants will receive TDF at birth and on Days 3 and 5 after birth. Cohort 4, which was added to the study based on a review of data from the other cohorts, will be similar to Cohort 3, except that infants will receive daily TDF for the 7 days after birth. Researchers believe this higher and more frequent dosing of TDF in infants will help them meet the target TDF concentration specified in the protocol. There will be seven study visits for women at study entry (Day 0), Day 2, between Days 5 and 7, at Weeks 6 and 12, and at Months 6 and 12 postpartum. Medical history, a short physical exam, and blood collection will occur at all visits. In Cohorts 1, 3, and 4, blood collection for PK studies will occur prior to receiving TDF and seven times post-dose. There will be eight study visits for infants, which will occur within 24 hours of birth; on Day 3; between Days 5 and 7; at Weeks 6 and 12; and at Months 6, 9, and 12. Medical history, a physical exam, and blood collection will occur at all visits. Infants will have x-rays to assess bone health at Day 3 and Month 3, except in Cohort 4, which will not include x-rays of infants. Infants of Cohort 1 will have blood collection for PK studies at birth and four times after birth. Infants of Cohorts 2 and 3 will undergo blood collections for PK studies at birth, Day 3, and Day 5. Blood collection at these visits will occur before receiving TDF and 2 and 10 hours after receiving TDF. At birth, an additional collection will occur 18 to 24 hours after receiving TDF, and on Day 5, two additional collections will occur--at 18 to 24 hours and at 36 to 48 hours after receiving TDF. Infants of Cohort 4 will have blood collection for PK studies at birth and after their fourth and seventh doses of TDF. Official Title ----------------- A Phase I Open Label Trial of the Safety and Pharmacokinetics of Tenofovir Disoproxil Fumarate in HIV-1 Infected Pregnant Women and Their Infants Conditions ----------------- HIV Infections Intervention / Treatment ----------------- * Drug: Tenofovir disoproxil fumarate * Drug: Tenofovir disoproxil fumarate * Drug: Tenofovir disoproxil fumarate Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria for HIV Infected Pregnant Women: HIV-1 infected Intend to deliver at the study site Willing to be contacted or visited at home Willing to be admitted to and remain in the delivery facility through Day 3 postpartum (Cohort 1) or Day 7 postpartum (Cohorts 2 and 3) Exclusion Criteria for HIV Infected Pregnant Women: Prior treatment with TDF Active opportunistic infection Serious bacterial infection Chronic malabsorption or diarrhea during the current pregnancy Clinically significant disease or condition that, in the opinion of the study clinician, would interfere with the study Known multiple gestation (twins, etc.) prior to study entry Participation in any other therapeutic or vaccine trial during the current pregnancy Use of certain medications Any other condition or situation that, in the opinion of the investigator, would interfere with the study For Cohort 4, use of atazanavir or lopinavir/ritonavir (Kaletra) within 2 weeks of anticipated delivery Exclusion Criteria for Infants Born to HIV Infected Pregnant Women: Birth weight of less than 2 kg (4.4 lbs) Severe congenital malformation or other medical condition that may affect survival and, in the opinion of the clinician, participation in this study Grade 2 or higher serum creatinine level or any other Grade 3 or higher toxicity Part of a multiple birth (twins, etc.) Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: 1<br>Pregnant participants will receive a single dose of TDF during active labor. These participants will be hospitalized at the delivery facility through Day 3 postpartum. | Drug: Tenofovir disoproxil fumarate<br>* 600-mg tablet taken orally once daily<br>* Other names: TDF;| | Experimental: 2<br>Pregnant participants will not receive TDF. Participants will be hospitalized at the delivery facility through Day 7 postpartum. Their infants will receive TDF at birth and on Days 3 and 5 after birth. | Drug: Tenofovir disoproxil fumarate<br>* 4-mg/kg oral suspension taken at birth and on Days 3 and 5 after birth<br>* Other names: TDF;| | Experimental: 3<br>Pregnant participants will be hospitalized at the delivery facility through Day 7 postpartum. They will receive TDF during active labor and their infants will receive TDF at birth and on Days 3 and 5 after birth. | Drug: Tenofovir disoproxil fumarate<br>* 600-mg tablet taken orally once daily<br>* Other names: TDF;Drug: Tenofovir disoproxil fumarate<br>* 4-mg/kg oral suspension taken at birth and on Days 3 and 5 after birth<br>* Other names: TDF;| | Experimental: 4<br>Pregnant participants will be hospitalized at the delivery facility through Day 7 postpartum. Mothers will receive TDF during active labor and their infants will receive TDF at birth and daily for 7 days after birth. | Drug: Tenofovir disoproxil fumarate<br>* 600-mg tablet taken orally once daily<br>* Other names: TDF;Drug: Tenofovir disoproxil fumarate<br>* 6-mg/kg oral suspension taken at birth and daily for 7 days after birth<br>* Other names: TDF;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Frequency of adverse events with a severity of Grade 3 or higher attributable to receipt of TDF | | Throughout study | | Maintenance of infant serum concentrations of TDF greater than 50 ng/ml | | Through Week 1 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maternal HIV-1 RNA levels | | At study entry, Days 5 to 7, and Week 6 | | Viral resistance to TDF in all HIV-1 infected infants, all of the corresponding mothers (transmitters), and a subset of mothers whose infants are not infected (nontransmitters). Analysis of TDF in mothers may include testing of breastmilk samples. | | Throughout study | | HIV infection in infants | | Throughout study | | TDF concentration in amniotic fluid and breast milk | | Through Week 1 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- MTCT, Perinatal Transmission, HIV Seronegativity

NCT03876106

A Study of LUT014 in Patients With Metastatic Colorectal Cancer With EGFR Inhibitor Induced Acneiform Lesions

The purpose of this phase 1, multicenter study is to evaluate the safety, tolerability and preliminary efficacy of LUT014 in adult metastatic colorectal cancer patients with EGFR Inhibitor induced acneiform lesions

A Phase 1, Open-Label, Dose Escalation Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy Study of Topically Administered LUT014 in Metastatic Colorectal Cancer Patients With EGFR Inhibitor Induced Acneiform Lesions

EGFR Inhibitor Induced Acneiform Lesions

* Drug: LUT014

Inclusion Criteria:~Diagnosed with mCRC;~Currently being treated with an FDA approved EGFRI for the treatment of mCRC, including but not limited to Erbitux® (cetuximab) Injection and Vectibix® (panitumumab) Injection, as directed by the approved labeling;~Treatment with the FDA approved EGFRI initiated within 12 weeks prior to the Screening Visit;~Grade 1 or 2 acneiform lesions at the Screening and Baseline (Day 0) Visits; A minimum of 3 subjects per dose cohort must have Grade 2 non-infected acneiform lesions at the Screening and Baseline (Day 0) Visits;~Age ≥18 years at the time of signing the informed consent form (ICF);~Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2;~Expected life expectancy greater than 3 months;~Subject can understand and sign the ICF, can communicate with the Investigator, can understand and comply with the requirements of the protocol, and can apply the study drug by himself/herself or has a care giver that can apply the drug;~Women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at baseline (Day 0);~WCBP must agree to abstain from sex or use an adequate method of contraception from the time of informed consent through the Day 55 Visit and for 90 days after the last dose of study drug (LUT014);~Males must abstain from sex with WCBP or use an adequate method of contraception from the time of informed consent through the Day 55 Visit and for 90 days after the last dose of study drug (LUT014).~Exclusion Criteria:~Active infection;~Significant skin disease other than EGFRI induced acneiform lesions;~Any cancer other than mCRC within 3 years of Screening;~Any condition which, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study;~Clinically relevant serious co-morbid medical conditions including, but not limited to, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias, chronic obstructive or chronic restrictive pulmonary disease, active central nervous system (CNS) disease uncontrolled by standard of care, known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements;~Pregnant or lactating;~Treatment with an EGFRI other than those specified in the inclusion criteria within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;~Treatment with a serine/threonine-protein kinase B-Raf (B-Raf) inhibitor, including but not limited to Zelboraf® (vemurafenib), Tafinlar® (dabrafenib), BraftoviTM (encorafenib), and Nexavar® (sorafenib), within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;~Treatment with a systemic antibiotic within 7 days prior to Screening;~Treatment with a topical corticosteroid to the face, neck, or upper portion of the anterior or posterior chest within 14 days prior to Screening or treatment with a systemic corticosteroid within 14 days prior to Screening, except for low dose systemic corticosteroids (e.g., 8-20 mg dexamethasone or comparable) given for up to one or two days every two weeks as part of standard of care for the prevention or treatment of chemotherapy-induced nausea and vomiting (CINV) for subjects being treated with FDA-approved EGFRI and chemotherapy combinations for mCRC;~Treatment with an oral retinoid within 7 days prior to Screening;~Treatment with another investigational drug within 30 days or 5 half-lives of drug prior to Screening, whichever is longer;~Known hypersensitivity to the inactive ingredients of the study drug (LUT014).

18 Years

All

No

Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Sequential Assignment Interventional Model Description: 3+3 Dose escalation of LUT014 Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Safety and tolerability (maximum tolerated dose, MTD) of LUT014 topically applied qd for 4 weeks in metastatic colorectal cancer (mCRC) patients with epidermal growth factor receptor inhibitor (EGFRI) induced acneiform lesions. | | From Day 0 (following administration of the first dose of study drug) through the Day 55 |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maximum concentration (Cmax) in plasma after a single administration and after qd administrations for 8 days | | Pre-dose through Day 8 | | Time to maximum concentration (Tmax) in plasma after a single administration and after qd administrations for 8 days | | Pre-dose through Day 8 | | Area under the concentration-time curve from time zero to last measurable concentration (AUC0-T) | | Pre-dose through Day 8 | | Area under the concentration-time cure from time zero extrapolated to infinity (AUC0-∞) | | Pre-dose through Day 8 | | Plasma elimination half-life (t1/2) | | Pre-dose through Day 8 | | Plasma clearance (CL) | | Pre-dose through Day 8 | | Volume of distribution (Vd) | | Pre-dose through Day 8 | | NCI, Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 skin and subcutaneous tissue disorders grading scale performed locally by the Investigator | The scale contains 5 grades from 1 which demonstrates the mild form of the disease up to 5, defined as death. | Pre-dose through Day 55 | | MASCC Study Group EGFRI-dermatologic AE grading by central reader based on photographs | | Pre-dose through Day 55 | | Functional Assessment of Cancer Therapy-EGFRI 18 (FACT-EGFRI-18) on health-related quality of life (HRQoL) questionnaire | FACT-EGFRI-18 is a patient-reported outcomes questionnaire developed to assess the effect of EGFRI on health-related quality of life The questionnaire includes 18 questions, each should be graded from 0, not suffering from this side effect at all, up to 4, suffering greatly from this side effect | Pre-dose through Day 55 |

LUT014, Protein Kinase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: LUT014 dose level 1<br>LUT014 will be topically applied to the face, neck, and upper portion of the anterior and posterior chest once a day for 4 weeks. | Drug: LUT014<br>* Topical<br>| | Experimental: LUT014 dose level 2<br>LUT014 will be topically applied to the face, neck, and upper portion of the anterior and posterior chest once a day for 4 weeks. | Drug: LUT014<br>* Topical<br>| | Experimental: LUT014 dose level 3<br>LUT014 will be topically applied to the face, neck, and upper portion of the anterior and posterior chest once a day for 4 weeks. | Drug: LUT014<br>* Topical<br>|

A Study of LUT014 in Patients With Metastatic Colorectal Cancer With EGFR Inhibitor Induced Acneiform Lesions Study Overview ================= Brief Summary ----------------- The purpose of this phase 1, multicenter study is to evaluate the safety, tolerability and preliminary efficacy of LUT014 in adult metastatic colorectal cancer patients with EGFR Inhibitor induced acneiform lesions Official Title ----------------- A Phase 1, Open-Label, Dose Escalation Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy Study of Topically Administered LUT014 in Metastatic Colorectal Cancer Patients With EGFR Inhibitor Induced Acneiform Lesions Conditions ----------------- EGFR Inhibitor Induced Acneiform Lesions Intervention / Treatment ----------------- * Drug: LUT014 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Diagnosed with mCRC; Currently being treated with an FDA approved EGFRI for the treatment of mCRC, including but not limited to Erbitux® (cetuximab) Injection and Vectibix® (panitumumab) Injection, as directed by the approved labeling; Treatment with the FDA approved EGFRI initiated within 12 weeks prior to the Screening Visit; Grade 1 or 2 acneiform lesions at the Screening and Baseline (Day 0) Visits; A minimum of 3 subjects per dose cohort must have Grade 2 non-infected acneiform lesions at the Screening and Baseline (Day 0) Visits; Age ≥18 years at the time of signing the informed consent form (ICF); Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2; Expected life expectancy greater than 3 months; Subject can understand and sign the ICF, can communicate with the Investigator, can understand and comply with the requirements of the protocol, and can apply the study drug by himself/herself or has a care giver that can apply the drug; Women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at baseline (Day 0); WCBP must agree to abstain from sex or use an adequate method of contraception from the time of informed consent through the Day 55 Visit and for 90 days after the last dose of study drug (LUT014); Males must abstain from sex with WCBP or use an adequate method of contraception from the time of informed consent through the Day 55 Visit and for 90 days after the last dose of study drug (LUT014). Exclusion Criteria: Active infection; Significant skin disease other than EGFRI induced acneiform lesions; Any cancer other than mCRC within 3 years of Screening; Any condition which, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study; Clinically relevant serious co-morbid medical conditions including, but not limited to, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias, chronic obstructive or chronic restrictive pulmonary disease, active central nervous system (CNS) disease uncontrolled by standard of care, known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements; Pregnant or lactating; Treatment with an EGFRI other than those specified in the inclusion criteria within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer; Treatment with a serine/threonine-protein kinase B-Raf (B-Raf) inhibitor, including but not limited to Zelboraf® (vemurafenib), Tafinlar® (dabrafenib), BraftoviTM (encorafenib), and Nexavar® (sorafenib), within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer; Treatment with a systemic antibiotic within 7 days prior to Screening; Treatment with a topical corticosteroid to the face, neck, or upper portion of the anterior or posterior chest within 14 days prior to Screening or treatment with a systemic corticosteroid within 14 days prior to Screening, except for low dose systemic corticosteroids (e.g., 8-20 mg dexamethasone or comparable) given for up to one or two days every two weeks as part of standard of care for the prevention or treatment of chemotherapy-induced nausea and vomiting (CINV) for subjects being treated with FDA-approved EGFRI and chemotherapy combinations for mCRC; Treatment with an oral retinoid within 7 days prior to Screening; Treatment with another investigational drug within 30 days or 5 half-lives of drug prior to Screening, whichever is longer; Known hypersensitivity to the inactive ingredients of the study drug (LUT014). Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Sequential Assignment Interventional Model Description: 3+3 Dose escalation of LUT014 Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: LUT014 dose level 1<br>LUT014 will be topically applied to the face, neck, and upper portion of the anterior and posterior chest once a day for 4 weeks. | Drug: LUT014<br>* Topical<br>| | Experimental: LUT014 dose level 2<br>LUT014 will be topically applied to the face, neck, and upper portion of the anterior and posterior chest once a day for 4 weeks. | Drug: LUT014<br>* Topical<br>| | Experimental: LUT014 dose level 3<br>LUT014 will be topically applied to the face, neck, and upper portion of the anterior and posterior chest once a day for 4 weeks. | Drug: LUT014<br>* Topical<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Safety and tolerability (maximum tolerated dose, MTD) of LUT014 topically applied qd for 4 weeks in metastatic colorectal cancer (mCRC) patients with epidermal growth factor receptor inhibitor (EGFRI) induced acneiform lesions. | | From Day 0 (following administration of the first dose of study drug) through the Day 55 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maximum concentration (Cmax) in plasma after a single administration and after qd administrations for 8 days | | Pre-dose through Day 8 | | Time to maximum concentration (Tmax) in plasma after a single administration and after qd administrations for 8 days | | Pre-dose through Day 8 | | Area under the concentration-time curve from time zero to last measurable concentration (AUC0-T) | | Pre-dose through Day 8 | | Area under the concentration-time cure from time zero extrapolated to infinity (AUC0-∞) | | Pre-dose through Day 8 | | Plasma elimination half-life (t1/2) | | Pre-dose through Day 8 | | Plasma clearance (CL) | | Pre-dose through Day 8 | | Volume of distribution (Vd) | | Pre-dose through Day 8 | | NCI, Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 skin and subcutaneous tissue disorders grading scale performed locally by the Investigator | The scale contains 5 grades from 1 which demonstrates the mild form of the disease up to 5, defined as death. | Pre-dose through Day 55 | | MASCC Study Group EGFRI-dermatologic AE grading by central reader based on photographs | | Pre-dose through Day 55 | | Functional Assessment of Cancer Therapy-EGFRI 18 (FACT-EGFRI-18) on health-related quality of life (HRQoL) questionnaire | FACT-EGFRI-18 is a patient-reported outcomes questionnaire developed to assess the effect of EGFRI on health-related quality of life The questionnaire includes 18 questions, each should be graded from 0, not suffering from this side effect at all, up to 4, suffering greatly from this side effect | Pre-dose through Day 55 |

NCT04823130

Dupilumab Effect on Pruritus Neuro-mechanisms in Patients With Atopic Dermatitis

Primary Objective:~- Assess change in neuronal architecture following long term treatment with dupilumab in skin biopsies from atopic dermatitis (AD) participants with chronic pruritus.~Secondary Objectives:~Assess change in neuronal architecture following short term treatment with dupilumab and during follow-up in skin biopsies from AD participants with chronic pruritus.~To evaluate the efficacy of dupilumab in AD participants with chronic pruritus.~To evaluate the safety of dupilumab in adult participants with moderate-to-severe AD.

AD participants: A 20-week Observation Period including 16 weeks of treatment for AD participants and a 4-week follow-up period; Healthy participants: 8 days observation period.

A Multi-center, Exploratory Study to Assess Dupilumab Effect on Pruritus Neuro-mechanisms in Patients With Atopic Dermatitis

Dermatitis Atopic

* Drug: Dupilumab (SAR231893)

Inclusion criteria:~For AD participants~Male or female of greater than or equal to (>=)18 years of age inclusive, at the time of signing the informed consent form (ICF).~Diagnosed with moderate-to-severe chronic AD for at least 1 year before screening.~Eligible to be treated with dupilumab according to product monograph.~Pruritus lasting 6 or more weeks before baseline (Day 1).~Eczema Area and Severity Index (EASI) score >=12 at baseline.~Pruritus numerical rating scale (NRS) >=4 at baseline.~Investigator global assessment (IGA) score of >=3 at screening (on the 0 to 4 scale) at baseline.~Atopic dermatitis active lesions on the upper limbs or lower limbs suitable for a skin biopsy without oozing, bleeding, or infection on upper limbs or trunk.~Participants with acute AD lesions as determined by Investigator's judgment.~Stable treatment with non-prohibited medication or therapy during the study.~For Healthy participants~Male or female of >=18 years of age inclusive, at the time of signing the ICF.~Certified as generally healthy by a comprehensive clinical assessment.~Exclusion criteria:~For AD participants~Previous treatment with dupilumab stopped within 6 months of baseline due to inadequate response to dupilumab.~Skin conditions other than AD that can confound assessments in the opinion of the investigator.~Regular use (>2 visits per week) of a tanning booth/parlor within 4 weeks of the Screening Visit.~Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the participant's participation in the study.~Participants with active tuberculosis (TB) or non-TB mycobacterial infection, or a history of incompletely treated TB unless it is well documented the participant has been adequately treated and can now start treatment with a biologic agent~Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before the Screening Visit (Visit 1) or during the Screening Period.~Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit (Visit 1) or during the Screening Period.~Known or suspected immunodeficiency, including history of invasive opportunistic infections.~Active malignancy or history of malignancy within 5 years before the Baseline Visit, except completely treated in situ carcinoma of the cervix and completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.~Ocular disorder that in the opinion of the Investigator could adversely affect the individual's risk for study participation. Examples include, but are not limited to, individuals with a history of active cases of herpes keratitis, Sjogren's syndrome, keratoconjunctivitis sicca or dry eye syndrome that require daily use of supplemental lubrication or individuals with ocular conditions that require the use of ocular corticosteroids or cyclosporine.~History of systemic hypersensitivity or anaphylaxis to dupilumab or any other biologic therapy, including any excipient.~Participant with any other medical or psychological condition including relevant laboratory or electrocardiogram abnormalities at screening.~For healthy participants~Regular use (>2 visits per week) of a tanning booth/ parlor within 4 weeks of the Screening Visit.~Treatment with the following concomitant medications and procedures is prohibited within 4 weeks before the Screening Visit or 5 half-lives (whichever is longer) until End of Study Visit:~Topical medication~Analgesics~Immunomodulators~Antidepressants~Anti-anxiety drugs~Any Type 2 immune disorders uncontrolled Type 2 diabetes mellitus, Type 1 diabetes mellitus, neuropathy or any other neurological disease.~Any concomitant illness(es) or conditions that, in the Investigator's judgment, would adversely affect the participant's participation in the study or potentially affect any skin biopsy related read out.~Positive test for immunoglobulin E (IgE) antibodies.~The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

18 Years

All

Accepts Healthy Volunteers

Primary Purpose: Basic Science Allocation: Non-Randomized Intervention Model: Parallel Assignment Interventional Model Description: Healthy participants served as control group providing normal skin reference for baseline skin biopsy derived outcome measure and were matched for gender, age, race and anatomical site of skin biopsy. Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change From Baseline in Intraepidermal Nerve Fiber Density on Lesional Skin at Week 17 | Skin biopsies were used to analyze the epidermal nerve fiber density. Nerve fibers were visualized by staining consecutive sections for the pan-axonal marker protein gene product 9.5 (PGP9.5); and the basement membrane was visualized by staining for collagen type 4. Quantification of intraepidermal nerve fiber density was calculated by assessing nerve fibers crossing the basement membrane per square millimeter (F/mm^2). Data for this outcome measure was not planned to be collected and analyzed for healthy participant arm as pre-specified in protocol. | Baseline, Week 17 | | Percentage of Participants With Change From Baseline in Nerve Fiber Branching on Lesional Skin at Week 17 | Skin biopsies were used to analyze the epidermal nerve fiber branching. Nerve fibers were visualized by staining consecutive sections for the pan-axonal marker PGP9.5; and the basement membrane was visualized by staining for collagen type 4. Branching of epidermal nerve fibers was assessed semi-quantitatively by classifying participants into 4 groups depending on the predominant intraepidermal nerve fiber branching pattern as follows: only linear (100% linear), mainly linear (>60% linear), mainly branched (>60% branched), only branched (100% branched). Percentage of participants with change in nerve fiber branching status from baseline on lesional skin at Week 17 are reported in this outcome measure. | Baseline, Week 17 |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change From Baseline in Intraepidermal Nerve Fiber Density on Lesional Skin at Weeks 3 and 21 | Skin biopsies were used to analyze the epidermal nerve fiber density. Nerve fibers were visualized by staining consecutive sections for the pan-axonal marker PGP9.5; and the basement membrane was visualized by staining for collagen type 4. Quantification of intraepidermal nerve fiber density was calculated by assessing nerve fibers crossing the basement membrane per square millimeter (F/mm^2). | Baseline, Weeks 3 and 21 | | Change From Baseline in Nerve Fiber Branching on Lesional Skin at Weeks 3 and 21 | Skin biopsies were used to analyze the epidermal nerve fiber branching. Nerve fibers were visualized by staining consecutive sections for the pan-axonal marker PGP9.5; and the basement membrane was visualized by staining for collagen type 4. Branching of epidermal nerve fibers was assessed semi-quantitatively by classifying participants into 4 groups depending on the predominant intraepidermal nerve fiber branching pattern as follows: only linear (100% linear), mainly linear (>60% linear), mainly branched (>60% branched), only branched (100% branched). | Baseline, Weeks 3 and 21 | | Change From Baseline in Peak Pruritus Assessed by Numeric Rating Scale (NRS) Scores at Weeks 17 and 21 | Peak Pruritus NRS was an assessment tool used to report the intensity of participant's pruritus (itch) during a daily recall period. Participants were asked to rate their worst itch on a 0 (No itch) to 10 (Worst itch imaginable) NRS by answering the following question: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Higher scores indicated greater severity. | Baseline, Weeks 17 and 21 | | Change From Baseline in Eczema and Severity Index (EASI) Total Score at Weeks 17 and 21 | EASI was a validated measure used to assess the severity and extent of AD. Four AD disease characteristics (erythema, thickness [induration, papulation, and edema], scratching [excoriation], and lichenification) were each assessed for severity by the Investigator on a scale of 0 (absent) through 3 (severe). EASI area score was based upon percent (%) body surface area (BSA) with AD in each body region: 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), and 6 (90% to 100%). Total EASI score was derived as the sum of the 4 region scores and ranged from 0 (minimum) to 72 (maximum). Higher scores indicated greater severity of AD. | Baseline, Weeks 17 and 21 | | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Weeks 17 and 21 | SCORAD was used to standardize the extent and severity of AD. It consisted of 3 components i.e., A =extent or affected BSA assessed as a % of each defined body area and reported as sum of all areas, with a maximum score of 100%. B=severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using following scale: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points) and C=subjective symptoms scored by participants on VAS, where 0=no itch (or no sleeplessness) and 10=worst imaginable itch (or sleeplessness) with a maximum score of 20. SCORAD total score was calculated using these 3 aspects: extent (A: 0-100), severity (B: 0-18), and subjective symptoms (C: 0-20) using the formula: A/5 + 7*B/2+ C. SCORAD total score ranged from 0 to 103, where 0 = no disease to 103 = severe disease. Higher values of SCORAD represent worse outcome. | Baseline, Weeks 17 and 21 | | Change From Baseline in Patient-Reported Outcomes Measurement Information (PROMIS-itch) Itch-Severity Total Score at Weeks 17 and 21 | PROMIS-itch represents a novel suite of participant-reported outcome (PRO) measures for the itch. The PROMIS-Itch severity score consists of 7 questions: 4 questions scored on a scale of 1 to 5: 1) How intense was your itch at its worst; 2) How intense was your itch in general; 3) What is your level of itch right now; 4) How often did you feel the itch; and rest 3 questions (same questions as 1 to 3 mentioned before but scaled on a scale of 0 to 10) were scored on a scale of 0 to 10. Higher scores for each question indicated worse outcome. The total PROMIS-itch score was calculated as the sum of the 7 questions and ranged from 4 (better outcome) to 50 (worse outcome), where a higher score indicated worse condition. | Baseline, Weeks 17 and 21 | | Change From Baseline in Patient Oriented Eczema Measure (POEM) Total Score at Weeks 17 and 21 | The POEM was a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults with AD. The format is participant response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on symptom frequency during the past week (i.e., 0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). Higher scores indicated more severe disease and poor quality of life. | Baseline, Weeks 17 and 21 | | Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Weeks 17 and 21 | DLQI was a 10-item PRO questionnaire that measured the impact of AD disease symptoms and treatment on quality of life. Each question was evaluated on a 4-point scale ranged from 0 to 3 where, 0 = not at all, 1= a little, 2= a lot, 3= very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score that ranged from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants. | Baseline, Weeks 17 and 21 | | Change From Baseline in Atopic Dermatitis Control Tool (ADCT) Total Score at Weeks 17 and 21 | ADCT was a PRO questionnaire designed to assess participant-self-perceived control of their eczema. ADCT contained 6 items allowing a comprehensive coverage of the dimensions defining AD control, i.e., overall severity of AD symptoms, frequency of intense episodes of itching, extent of AD related bother, impact on sleep, impact on daily activities, impact on mood or emotions. Each item of the ADCT is rated from 0 (no problem) to 4 (worst) Likert scale and is equally weighted. The sum of the 6 items gives the total score that ranged from 0 (best disease control) to 24 (worst disease control). Higher scores indicate lower AD control. | Baseline, Weeks 17 and 21 | | Change From Baseline in Sleep Quality Numerical Rating Scale Score at Weeks 17 and 21 | Sleep quality NRS was used to assess the quality of the participant's previous night's sleep using a 0 (Worst possible sleep) to 10 (Best possible sleep) NRS. Participants were asked to complete the following question upon awakening: Select the number (0 to 10) that best describes the quality of your sleep last night. Higher score indicated better outcome. | Baseline, Weeks 17 and 21 | | Change From Baseline in Skin Pain Numerical Rating Scale Score at Weeks 17 and 21 | Skin pain NRS was used to assess participant's skin pain at its worst in the past 24 hours using a 0 (Not at all) to 10 (Very much) NRS. Participants were asked the following question: Think about all the areas of your skin with eczema. How much did your skin burn at its worst in the past 24 hours? Lower score indicated better outcome. | Baseline, Weeks 17 and 21 | | Change From Baseline in Skin Sensitivity Numerical Rating Scale Score at Weeks 17 and 21 | Skin sensitivity NRS was a 1 item PRO measure asking the participants to rate their skin sensitivity to touch using a 0 (Normal) to 10 (Extremely sensitive) NRS. Participants were asked the following question: Think about all the areas of your skin with eczema. How sensitive was your skin at its worst in the past 24 hours? Lower score indicated better outcome. | Baseline, Weeks 17 and 21 | | Change From Baseline in Skin Burning Numerical Rating Scale Score at Weeks 17 and 21 | Skin burning NRS was a 1-item PRO measure asking participants to rate the burning sensation of their skin in the past 24 hours using a 0 (Not at all) to 10 (Very much) NRS. Participants were asked the following question: Think about all the areas of your skin with eczema. How much did your skin burn at its worst in the past 24 hours? Lower score indicated better outcome. | Baseline, Weeks 17 and 21 | | Percentage of Participants With Change of Greater Than or Equal to (>=4) Point in Pruritus Numerical Rating Scale From Baseline at Weeks 17 and 21 | Pruritus NRS was an assessment tool used to report the intensity of participant's pruritus (itch) during a daily recall period. Participants were asked to rate their worst itch on a 0 (No itch) to 10 (Worst itch imaginable) NRS by answering the following question: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Higher scores indicated greater severity. Percentage of participants with change of >=4 point in pruritus NRS scale from baseline at Weeks 17 and 21 are reported in this outcome measure. | Baseline, Weeks 17 and 21 |

Dermatitis, Atopic, Dermatitis, Pruritus, Skin Diseases, Skin Diseases, Genetic, Genetic Diseases, Inborn, Skin Diseases, Eczematous, Hypersensitivity, Immediate, Hypersensitivity, Immune System Diseases, Skin Manifestations

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | No Intervention: Healthy Participants: Control<br>Healthy participants with site, age, gender, race, location of targeted lesional and non-lesional skin area matched to selected AD participants, received no treatment, and were considered as a control group. | | | Experimental: Participants With AD: Dupilumab<br>Participants with moderate to severe AD received dupilumab 600 milligrams (mg) subcutaneous (SC) injection on Day 1, followed by dupilumab 300 mg SC injection every 2 weeks (Q2W) from Week 3 to Week 15. | Drug: Dupilumab (SAR231893)<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>* Other names: REGN668;|

Dupilumab Effect on Pruritus Neuro-mechanisms in Patients With Atopic Dermatitis Study Overview ================= Brief Summary ----------------- Primary Objective: - Assess change in neuronal architecture following long term treatment with dupilumab in skin biopsies from atopic dermatitis (AD) participants with chronic pruritus. Secondary Objectives: Assess change in neuronal architecture following short term treatment with dupilumab and during follow-up in skin biopsies from AD participants with chronic pruritus. To evaluate the efficacy of dupilumab in AD participants with chronic pruritus. To evaluate the safety of dupilumab in adult participants with moderate-to-severe AD. Detailed Description ----------------- AD participants: A 20-week Observation Period including 16 weeks of treatment for AD participants and a 4-week follow-up period; Healthy participants: 8 days observation period. Official Title ----------------- A Multi-center, Exploratory Study to Assess Dupilumab Effect on Pruritus Neuro-mechanisms in Patients With Atopic Dermatitis Conditions ----------------- Dermatitis Atopic Intervention / Treatment ----------------- * Drug: Dupilumab (SAR231893) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria: For AD participants Male or female of greater than or equal to (>=)18 years of age inclusive, at the time of signing the informed consent form (ICF). Diagnosed with moderate-to-severe chronic AD for at least 1 year before screening. Eligible to be treated with dupilumab according to product monograph. Pruritus lasting 6 or more weeks before baseline (Day 1). Eczema Area and Severity Index (EASI) score >=12 at baseline. Pruritus numerical rating scale (NRS) >=4 at baseline. Investigator global assessment (IGA) score of >=3 at screening (on the 0 to 4 scale) at baseline. Atopic dermatitis active lesions on the upper limbs or lower limbs suitable for a skin biopsy without oozing, bleeding, or infection on upper limbs or trunk. Participants with acute AD lesions as determined by Investigator's judgment. Stable treatment with non-prohibited medication or therapy during the study. For Healthy participants Male or female of >=18 years of age inclusive, at the time of signing the ICF. Certified as generally healthy by a comprehensive clinical assessment. Exclusion criteria: For AD participants Previous treatment with dupilumab stopped within 6 months of baseline due to inadequate response to dupilumab. Skin conditions other than AD that can confound assessments in the opinion of the investigator. Regular use (>2 visits per week) of a tanning booth/parlor within 4 weeks of the Screening Visit. Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the participant's participation in the study. Participants with active tuberculosis (TB) or non-TB mycobacterial infection, or a history of incompletely treated TB unless it is well documented the participant has been adequately treated and can now start treatment with a biologic agent Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before the Screening Visit (Visit 1) or during the Screening Period. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit (Visit 1) or during the Screening Period. Known or suspected immunodeficiency, including history of invasive opportunistic infections. Active malignancy or history of malignancy within 5 years before the Baseline Visit, except completely treated in situ carcinoma of the cervix and completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin. Ocular disorder that in the opinion of the Investigator could adversely affect the individual's risk for study participation. Examples include, but are not limited to, individuals with a history of active cases of herpes keratitis, Sjogren's syndrome, keratoconjunctivitis sicca or dry eye syndrome that require daily use of supplemental lubrication or individuals with ocular conditions that require the use of ocular corticosteroids or cyclosporine. History of systemic hypersensitivity or anaphylaxis to dupilumab or any other biologic therapy, including any excipient. Participant with any other medical or psychological condition including relevant laboratory or electrocardiogram abnormalities at screening. For healthy participants Regular use (>2 visits per week) of a tanning booth/ parlor within 4 weeks of the Screening Visit. Treatment with the following concomitant medications and procedures is prohibited within 4 weeks before the Screening Visit or 5 half-lives (whichever is longer) until End of Study Visit: Topical medication Analgesics Immunomodulators Antidepressants Anti-anxiety drugs Any Type 2 immune disorders uncontrolled Type 2 diabetes mellitus, Type 1 diabetes mellitus, neuropathy or any other neurological disease. Any concomitant illness(es) or conditions that, in the Investigator's judgment, would adversely affect the participant's participation in the study or potentially affect any skin biopsy related read out. Positive test for immunoglobulin E (IgE) antibodies. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Non-Randomized Intervention Model: Parallel Assignment Interventional Model Description: Healthy participants served as control group providing normal skin reference for baseline skin biopsy derived outcome measure and were matched for gender, age, race and anatomical site of skin biopsy. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | No Intervention: Healthy Participants: Control<br>Healthy participants with site, age, gender, race, location of targeted lesional and non-lesional skin area matched to selected AD participants, received no treatment, and were considered as a control group. | | | Experimental: Participants With AD: Dupilumab<br>Participants with moderate to severe AD received dupilumab 600 milligrams (mg) subcutaneous (SC) injection on Day 1, followed by dupilumab 300 mg SC injection every 2 weeks (Q2W) from Week 3 to Week 15. | Drug: Dupilumab (SAR231893)<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>* Other names: REGN668;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change From Baseline in Intraepidermal Nerve Fiber Density on Lesional Skin at Week 17 | Skin biopsies were used to analyze the epidermal nerve fiber density. Nerve fibers were visualized by staining consecutive sections for the pan-axonal marker protein gene product 9.5 (PGP9.5); and the basement membrane was visualized by staining for collagen type 4. Quantification of intraepidermal nerve fiber density was calculated by assessing nerve fibers crossing the basement membrane per square millimeter (F/mm^2). Data for this outcome measure was not planned to be collected and analyzed for healthy participant arm as pre-specified in protocol. | Baseline, Week 17 | | Percentage of Participants With Change From Baseline in Nerve Fiber Branching on Lesional Skin at Week 17 | Skin biopsies were used to analyze the epidermal nerve fiber branching. Nerve fibers were visualized by staining consecutive sections for the pan-axonal marker PGP9.5; and the basement membrane was visualized by staining for collagen type 4. Branching of epidermal nerve fibers was assessed semi-quantitatively by classifying participants into 4 groups depending on the predominant intraepidermal nerve fiber branching pattern as follows: only linear (100% linear), mainly linear (>60% linear), mainly branched (>60% branched), only branched (100% branched). Percentage of participants with change in nerve fiber branching status from baseline on lesional skin at Week 17 are reported in this outcome measure. | Baseline, Week 17 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change From Baseline in Intraepidermal Nerve Fiber Density on Lesional Skin at Weeks 3 and 21 | Skin biopsies were used to analyze the epidermal nerve fiber density. Nerve fibers were visualized by staining consecutive sections for the pan-axonal marker PGP9.5; and the basement membrane was visualized by staining for collagen type 4. Quantification of intraepidermal nerve fiber density was calculated by assessing nerve fibers crossing the basement membrane per square millimeter (F/mm^2). | Baseline, Weeks 3 and 21 | | Change From Baseline in Nerve Fiber Branching on Lesional Skin at Weeks 3 and 21 | Skin biopsies were used to analyze the epidermal nerve fiber branching. Nerve fibers were visualized by staining consecutive sections for the pan-axonal marker PGP9.5; and the basement membrane was visualized by staining for collagen type 4. Branching of epidermal nerve fibers was assessed semi-quantitatively by classifying participants into 4 groups depending on the predominant intraepidermal nerve fiber branching pattern as follows: only linear (100% linear), mainly linear (>60% linear), mainly branched (>60% branched), only branched (100% branched). | Baseline, Weeks 3 and 21 | | Change From Baseline in Peak Pruritus Assessed by Numeric Rating Scale (NRS) Scores at Weeks 17 and 21 | Peak Pruritus NRS was an assessment tool used to report the intensity of participant's pruritus (itch) during a daily recall period. Participants were asked to rate their worst itch on a 0 (No itch) to 10 (Worst itch imaginable) NRS by answering the following question: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Higher scores indicated greater severity. | Baseline, Weeks 17 and 21 | | Change From Baseline in Eczema and Severity Index (EASI) Total Score at Weeks 17 and 21 | EASI was a validated measure used to assess the severity and extent of AD. Four AD disease characteristics (erythema, thickness [induration, papulation, and edema], scratching [excoriation], and lichenification) were each assessed for severity by the Investigator on a scale of 0 (absent) through 3 (severe). EASI area score was based upon percent (%) body surface area (BSA) with AD in each body region: 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), and 6 (90% to 100%). Total EASI score was derived as the sum of the 4 region scores and ranged from 0 (minimum) to 72 (maximum). Higher scores indicated greater severity of AD. | Baseline, Weeks 17 and 21 | | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Weeks 17 and 21 | SCORAD was used to standardize the extent and severity of AD. It consisted of 3 components i.e., A =extent or affected BSA assessed as a % of each defined body area and reported as sum of all areas, with a maximum score of 100%. B=severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using following scale: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points) and C=subjective symptoms scored by participants on VAS, where 0=no itch (or no sleeplessness) and 10=worst imaginable itch (or sleeplessness) with a maximum score of 20. SCORAD total score was calculated using these 3 aspects: extent (A: 0-100), severity (B: 0-18), and subjective symptoms (C: 0-20) using the formula: A/5 + 7*B/2+ C. SCORAD total score ranged from 0 to 103, where 0 = no disease to 103 = severe disease. Higher values of SCORAD represent worse outcome. | Baseline, Weeks 17 and 21 | | Change From Baseline in Patient-Reported Outcomes Measurement Information (PROMIS-itch) Itch-Severity Total Score at Weeks 17 and 21 | PROMIS-itch represents a novel suite of participant-reported outcome (PRO) measures for the itch. The PROMIS-Itch severity score consists of 7 questions: 4 questions scored on a scale of 1 to 5: 1) How intense was your itch at its worst; 2) How intense was your itch in general; 3) What is your level of itch right now; 4) How often did you feel the itch; and rest 3 questions (same questions as 1 to 3 mentioned before but scaled on a scale of 0 to 10) were scored on a scale of 0 to 10. Higher scores for each question indicated worse outcome. The total PROMIS-itch score was calculated as the sum of the 7 questions and ranged from 4 (better outcome) to 50 (worse outcome), where a higher score indicated worse condition. | Baseline, Weeks 17 and 21 | | Change From Baseline in Patient Oriented Eczema Measure (POEM) Total Score at Weeks 17 and 21 | The POEM was a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults with AD. The format is participant response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on symptom frequency during the past week (i.e., 0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). Higher scores indicated more severe disease and poor quality of life. | Baseline, Weeks 17 and 21 | | Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Weeks 17 and 21 | DLQI was a 10-item PRO questionnaire that measured the impact of AD disease symptoms and treatment on quality of life. Each question was evaluated on a 4-point scale ranged from 0 to 3 where, 0 = not at all, 1= a little, 2= a lot, 3= very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score that ranged from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants. | Baseline, Weeks 17 and 21 | | Change From Baseline in Atopic Dermatitis Control Tool (ADCT) Total Score at Weeks 17 and 21 | ADCT was a PRO questionnaire designed to assess participant-self-perceived control of their eczema. ADCT contained 6 items allowing a comprehensive coverage of the dimensions defining AD control, i.e., overall severity of AD symptoms, frequency of intense episodes of itching, extent of AD related bother, impact on sleep, impact on daily activities, impact on mood or emotions. Each item of the ADCT is rated from 0 (no problem) to 4 (worst) Likert scale and is equally weighted. The sum of the 6 items gives the total score that ranged from 0 (best disease control) to 24 (worst disease control). Higher scores indicate lower AD control. | Baseline, Weeks 17 and 21 | | Change From Baseline in Sleep Quality Numerical Rating Scale Score at Weeks 17 and 21 | Sleep quality NRS was used to assess the quality of the participant's previous night's sleep using a 0 (Worst possible sleep) to 10 (Best possible sleep) NRS. Participants were asked to complete the following question upon awakening: Select the number (0 to 10) that best describes the quality of your sleep last night. Higher score indicated better outcome. | Baseline, Weeks 17 and 21 | | Change From Baseline in Skin Pain Numerical Rating Scale Score at Weeks 17 and 21 | Skin pain NRS was used to assess participant's skin pain at its worst in the past 24 hours using a 0 (Not at all) to 10 (Very much) NRS. Participants were asked the following question: Think about all the areas of your skin with eczema. How much did your skin burn at its worst in the past 24 hours? Lower score indicated better outcome. | Baseline, Weeks 17 and 21 | | Change From Baseline in Skin Sensitivity Numerical Rating Scale Score at Weeks 17 and 21 | Skin sensitivity NRS was a 1 item PRO measure asking the participants to rate their skin sensitivity to touch using a 0 (Normal) to 10 (Extremely sensitive) NRS. Participants were asked the following question: Think about all the areas of your skin with eczema. How sensitive was your skin at its worst in the past 24 hours? Lower score indicated better outcome. | Baseline, Weeks 17 and 21 | | Change From Baseline in Skin Burning Numerical Rating Scale Score at Weeks 17 and 21 | Skin burning NRS was a 1-item PRO measure asking participants to rate the burning sensation of their skin in the past 24 hours using a 0 (Not at all) to 10 (Very much) NRS. Participants were asked the following question: Think about all the areas of your skin with eczema. How much did your skin burn at its worst in the past 24 hours? Lower score indicated better outcome. | Baseline, Weeks 17 and 21 | | Percentage of Participants With Change of Greater Than or Equal to (>=4) Point in Pruritus Numerical Rating Scale From Baseline at Weeks 17 and 21 | Pruritus NRS was an assessment tool used to report the intensity of participant's pruritus (itch) during a daily recall period. Participants were asked to rate their worst itch on a 0 (No itch) to 10 (Worst itch imaginable) NRS by answering the following question: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Higher scores indicated greater severity. Percentage of participants with change of >=4 point in pruritus NRS scale from baseline at Weeks 17 and 21 are reported in this outcome measure. | Baseline, Weeks 17 and 21 |

NCT04857125

Prevention of Postoperative Delirium After Acute Surgery

The aim of this trial is to evaluate the implementation and effect of an evidence based, multicomponent intervention on postoperative delirium, when fast implemented throughout the patients stay in hospital before, during and after acute surgery in a risk population, the primary outcome being frequency of patients with positive Confusion Assessment Method (CAM) score.~The hypothesis is that the frequency of postoperative delirium will be reduced after implementation of the preventive interventions.

Prevention of Delirium After Acute Surgery - Implementation of a Multicomponent Intervention Throughout the Hospitalization

Postoperative Delirium

* Other: Patient interventions * Other: Staff education

Inclusion Criteria:~Patients aged 40 or above.~Patients scheduled for acute abdominal or orthopaedic surgery in general anaesthesia with an expected duration of 30 minutes or more.~Patients who are scheduled for surgery within 72 hours of hospital admission.~Patients who are expected to stay in hospital for 24 hours or more.~Exclusion Criteria:~Patients screened CAM positive before surgery.~Patients who have already been included in the study~Patients unable to speak and read Danish.~Inability to provide consent.

40 Years

All

No

Primary Purpose: Prevention Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: Single

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Postoperative delirium identified with the screening tool Confusion Assessment Method (CAM), assessing change from negative to positive score. | Patients are screened with the tool Confusion Assessment Method (CAM). A patient will be considered CAM positive, according to the CAM algorithm for diagnosis of delirium that requires the presence of both the first (acute onset and fluctuating course) and the second criteria (inattention) and of either the third (disorganised thinking) or the fourth criterion (altered level of consciousness). | During the 5 initial postoperative in-hospital days. Patients are screened twice a day; in the morning (7-10 AM) and in the evening (7-11 PM). |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Inadequate emergence identified with the screening tool Confusion Assessment Method (CAM) in the Post-Anaesthesia Care Unit (PACU), assessing change from negative to positive score. | Patients are screened with the tool Confusion Assessment Method (CAM) in the Post-Anaesthesia Care Unit (PACU). A patient will be considered CAM positive, according to the CAM algorithm for diagnosis of delirium that requires the presence of both the first (acute onset and fluctuating course) and the second criteria (inattention) and of either the third (disorganised thinking) or the fourth criterion (altered level of consciousness). A positive CAM score at any time during the PACU stay is considered as having Inadequate emergence, assessing change from negative to positive score. | Patients are screened at time of arrival and until discharge from PACU | | All-cause mortality within 30 days. | All-cause mortality | Day 30 | | Length of postoperative stay (LOS). | Length of postoperative stay in hospital | Day 30 | | Length of stay in the Post-Anaesthesia Care Unit (PACU) after surgery. | Length of stay in the Post-Anaesthesia Care Unit (PACU) after surgery after surgery will be assessed. | Day 30 | | Number of participants who are readmitted to hospital within 30 days. | Re-admissions are defined as an acute admission which takes place between 4 hours and 30 days after discharge from hospital. The readmission indicator is non-specific, as all readmissions are included, regardless of which hospital the readmission takes place and regardless of the diagnosis at readmission. | Day 30 | | Number of participants who are admitted to the intensive care unit after the operation. | Admission to the intensive care unit after the operation. | Day 30 | | Number of patients in need of re-operation | Need for re-operation due to complications | Day 30 |

Implementation, Prevention, Multicomponent intervention, Anaesthetics, General, Non-cardiac, Acute surgery, Non-pharmacological intervention, Postoperative care

Delirium, Emergence Delirium, Confusion, Neurobehavioral Manifestations, Neurologic Manifestations, Nervous System Diseases, Neurocognitive Disorders, Mental Disorders, Postoperative Complications, Pathologic Processes

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Multicomponent intervention<br>Pre-, intra- and postoperative interventions applied using the Fast-IM method. | Other: Patient interventions<br>* The multicomponent intervention consists of several elements regarding avoidance of specific pre-medications and optimising the patients condition before surgery (reducing fasting and fluid-fasting time).~Per-operative focus on using bispectral index (BIS) guided anaesthesia, Total intravenous anaesthesia (TIVA) as first choice, pain-and PONV (postoperative nausea and vomiting) prophylaxis and treatment.~Postoperative focus on: Reducing indwelling catheters, Fluid (p.o. or IV), Nutrition, Mobilisation, Sleep, Non-pharmacological interventions (Shielding, involving of relatives, orientation, optimizing of senses)<br>Other: Staff education<br>* Staff will be educated for at least 1-2 hours. Anaesthesiologist and nurse anaesthetists will receive a brush up on the use of bispectral index (BIS) and the intervention elements that are implemented and monitored. Staff in the PACU, as well as staff in the surgery wards, will be educated in postoperative delirium, learning to identify symptoms of delirium and how to use the screening tool CAM.<br>| | No Intervention: Standard care<br>Patients are receiving standard care. | |

Prevention of Postoperative Delirium After Acute Surgery Study Overview ================= Brief Summary ----------------- The aim of this trial is to evaluate the implementation and effect of an evidence based, multicomponent intervention on postoperative delirium, when fast implemented throughout the patients stay in hospital before, during and after acute surgery in a risk population, the primary outcome being frequency of patients with positive Confusion Assessment Method (CAM) score. The hypothesis is that the frequency of postoperative delirium will be reduced after implementation of the preventive interventions. Official Title ----------------- Prevention of Delirium After Acute Surgery - Implementation of a Multicomponent Intervention Throughout the Hospitalization Conditions ----------------- Postoperative Delirium Intervention / Treatment ----------------- * Other: Patient interventions * Other: Staff education Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients aged 40 or above. Patients scheduled for acute abdominal or orthopaedic surgery in general anaesthesia with an expected duration of 30 minutes or more. Patients who are scheduled for surgery within 72 hours of hospital admission. Patients who are expected to stay in hospital for 24 hours or more. Exclusion Criteria: Patients screened CAM positive before surgery. Patients who have already been included in the study Patients unable to speak and read Danish. Inability to provide consent. Ages Eligible for Study ----------------- Minimum Age: 40 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Multicomponent intervention<br>Pre-, intra- and postoperative interventions applied using the Fast-IM method. | Other: Patient interventions<br>* The multicomponent intervention consists of several elements regarding avoidance of specific pre-medications and optimising the patients condition before surgery (reducing fasting and fluid-fasting time). Per-operative focus on using bispectral index (BIS) guided anaesthesia, Total intravenous anaesthesia (TIVA) as first choice, pain-and PONV (postoperative nausea and vomiting) prophylaxis and treatment. Postoperative focus on: Reducing indwelling catheters, Fluid (p.o. or IV), Nutrition, Mobilisation, Sleep, Non-pharmacological interventions (Shielding, involving of relatives, orientation, optimizing of senses)<br>Other: Staff education<br>* Staff will be educated for at least 1-2 hours. Anaesthesiologist and nurse anaesthetists will receive a brush up on the use of bispectral index (BIS) and the intervention elements that are implemented and monitored. Staff in the PACU, as well as staff in the surgery wards, will be educated in postoperative delirium, learning to identify symptoms of delirium and how to use the screening tool CAM.<br>| | No Intervention: Standard care<br>Patients are receiving standard care. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Postoperative delirium identified with the screening tool Confusion Assessment Method (CAM), assessing change from negative to positive score. | Patients are screened with the tool Confusion Assessment Method (CAM). A patient will be considered CAM positive, according to the CAM algorithm for diagnosis of delirium that requires the presence of both the first (acute onset and fluctuating course) and the second criteria (inattention) and of either the third (disorganised thinking) or the fourth criterion (altered level of consciousness). | During the 5 initial postoperative in-hospital days. Patients are screened twice a day; in the morning (7-10 AM) and in the evening (7-11 PM). | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Inadequate emergence identified with the screening tool Confusion Assessment Method (CAM) in the Post-Anaesthesia Care Unit (PACU), assessing change from negative to positive score. | Patients are screened with the tool Confusion Assessment Method (CAM) in the Post-Anaesthesia Care Unit (PACU). A patient will be considered CAM positive, according to the CAM algorithm for diagnosis of delirium that requires the presence of both the first (acute onset and fluctuating course) and the second criteria (inattention) and of either the third (disorganised thinking) or the fourth criterion (altered level of consciousness). A positive CAM score at any time during the PACU stay is considered as having Inadequate emergence, assessing change from negative to positive score. | Patients are screened at time of arrival and until discharge from PACU | | All-cause mortality within 30 days. | All-cause mortality | Day 30 | | Length of postoperative stay (LOS). | Length of postoperative stay in hospital | Day 30 | | Length of stay in the Post-Anaesthesia Care Unit (PACU) after surgery. | Length of stay in the Post-Anaesthesia Care Unit (PACU) after surgery after surgery will be assessed. | Day 30 | | Number of participants who are readmitted to hospital within 30 days. | Re-admissions are defined as an acute admission which takes place between 4 hours and 30 days after discharge from hospital. The readmission indicator is non-specific, as all readmissions are included, regardless of which hospital the readmission takes place and regardless of the diagnosis at readmission. | Day 30 | | Number of participants who are admitted to the intensive care unit after the operation. | Admission to the intensive care unit after the operation. | Day 30 | | Number of patients in need of re-operation | Need for re-operation due to complications | Day 30 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Implementation, Prevention, Multicomponent intervention, Anaesthetics, General, Non-cardiac, Acute surgery, Non-pharmacological intervention, Postoperative care

NCT04156438

Airway Pressure Release Ventilation for Moderate-to-severe Acute Respiratory Distress Syndrome

This study will examine the feasibility of a large clinical trial investigating the effectiveness of airway pressure release ventilation and low tidal volume ventilation for patients with moderate-to-severe acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a disease that has an incidence of 5% of hospitalized mechanically ventilated patients. ARDS is associated with high morbidity and mortality in critically ill patients, with mortality reported as high as 45% in severe ARDS. Patients who develop ARDS will require mechanical ventilation. Patients with ARDS are graded by the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) into three categories of severity: mild (PaO2/FiO2 201-300 mm Hg), moderate (PaO2/FiO2 101-200 mmHg), and severe (PaO2/FiO2 ≤ 100).~Volutrauma and barotrauma are thought to contribute to the development of ARDS and alter mortality. The damage that occurs to the lungs manifests itself as inflammation, which leads to poor gas exchange of oxygen and carbon dioxide. Several strategies of lung-protective mechanical ventilation have been investigated in ARDS, including the use of low tidal volume ventilation (LTVV) or ARDSNet strategy, high frequency oscillation ventilation (HFOV), and airway pressure release ventilation (APRV). Lung protective strategies may be best beneficial prior to the onset of the development of ARDS or early in the course of the disease. As a result of the ARDSNet trial, LTVV has been adopted as the usual standard of care of ventilation and safest mode of ventilation for patients with ARDS.~Recently, APRV has been proposed as a potential alternative to LTVV. APRV is a form of ventilation that keeps the lungs inflated through the majority of the breath cycle and allows patients to breathe spontaneously above this level of inflation. APRV allows for spontaneous respiration with increased airway pressure, potentially allowing for decreased sedation, shorter duration of mechanical ventilation, and decreased need for vasopressors. APRV has been associated with possible reduction in incidence of ARDS and in-hospital mortality in non-randomized observational studies. In patients with established ARDS, the use of APRV has also not been well studied, with most studies limited to small observational studies often with no comparison group. One randomized trial using APRV alone had less than 30% of patients having a diagnosis of ARDS and did not show any difference in any outcomes. Recently, Zhou and colleagues conducted a randomized trial comparing APRV to conventional ventilation in 138 mechanically ventilated patients with mild to severe ARDS and found that APRV may shorten the duration of mechanical ventilation and reduce intensive care unit (ICU) length of stay.~While some of these studies had shown promise of APRV compared to LTVV, there has not been acceptance of APRV into guidelines as first line ventilation, and recommendations of institutions such as the Canadian Agency for Drugs and Technology in Health (CADTH) recommends interpreting these results with caution. Consequently, there remains clinical equipoise on this issue. Some ICU clinicians will currently use APRV as a rescue mode of ventilation in ARDS in their clinical practice while others will continue with the use of LTVV. We would like to randomize patients to LTVV or APRV and examine the feasibility of conducting a large multicentre randomized controlled trial in Canada.

Early Use of Airway Pressure ReLease Ventilation in Critically Ill Adults With Moderate-to-severe Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome

* Device: Low tidal volume ventilation * Device: Airway pressure release ventilation

Inclusion Criteria:~Fulfilling the diagnostic criteria of ARDS, according to the Berlin definition~Moderate to severe ARDS as defined as a PaO2: FiO2 ratio of ≤150 during invasive mechanical ventilation~Endotracheal intubation and mechanical ventilation for ARDS less than 48 hours~Exclusion Criteria:~Age less than 18 years~Pregnancy~Intracranial hypertension (suspected or confirmed)~Severe chronic obstructive pulmonary disease as defined by either:~FEV1/FVC less than 50% predicted, or~Chronic hypercarbia (PaCO2>45 mmHg), chronic hypoxemia (PaO2 < 55 mmHg) on room air, and/or elevated admission serum HCO3 >30 mmol/L~Presence of documented barotrauma, i.e. pneumothorax~Treatment with extracorporeal support (ECMO) at enrollment~Refractory shock~Advanced directives indicating preferences to not have advanced life support~Moribund patient, i.e. not expected to survive longer than 24 hours

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Informed consent rate | A successful informed consent rate will be defined as ≥70% of substitute decision makers or patients approached choosing to participate in this trial | Informed consent rate will be measured over a 1 year period of the pilot study | | Recruitment rate | A successful recruitment rate will be achieving at least 15 patients over the 1 year period. | Recruitment rate will be measured over the one year of the pilot study. | | Protocol adherence rate | An adherence rate of at least 80% will be considered successful. | Protocol adherence will be measured for each study patient, and compiled over the duration of the pilot study (i.e. 1 year). |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | 28-day mortality | Death, measured from time of enrollment until 28 days. | Up to Day 28 | | In-hospital mortality | Death, at hospital discharge | Up to 365 days | | ICU length of stay | Length of stay in the intensive care unit | Up to 365 days | | Hospital length of stay | Length of stay in the hospital in days | Up to 365 days | | Length/duration of mechanical ventilation | Length of time patient was on mechanical ventilation | Up to 365 days | | Incidence of tracheostomy | Incidence of tracheostomy during their ICU stay | Up to 365 days |

Airway pressure release ventilation, low tidal volume ventilation, APRV, ARDSNet ventilation, LTVV, acute respiratory distress syndrome, ARDS

Respiratory Distress Syndrome, Respiratory Distress Syndrome, Newborn, Acute Lung Injury, Syndrome, Disease, Pathologic Processes, Lung Diseases, Respiratory Tract Diseases, Respiration Disorders, Infant, Premature, Diseases, Infant, Newborn, Diseases, Lung Injury

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Low tidal volume ventilation<br>Conventional low tidal volume ventilation | Device: Low tidal volume ventilation<br>* Conventional ventilation strategy for patient with ARDS<br>| | Experimental: Airway pressure release ventilation<br>Early use of airway pressure release ventilation | Device: Airway pressure release ventilation<br>* Experimental ventilation protocol for patients with ARDS<br>|

Airway Pressure Release Ventilation for Moderate-to-severe Acute Respiratory Distress Syndrome Study Overview ================= Brief Summary ----------------- This study will examine the feasibility of a large clinical trial investigating the effectiveness of airway pressure release ventilation and low tidal volume ventilation for patients with moderate-to-severe acute respiratory distress syndrome. Detailed Description ----------------- Acute respiratory distress syndrome (ARDS) is a disease that has an incidence of 5% of hospitalized mechanically ventilated patients. ARDS is associated with high morbidity and mortality in critically ill patients, with mortality reported as high as 45% in severe ARDS. Patients who develop ARDS will require mechanical ventilation. Patients with ARDS are graded by the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) into three categories of severity: mild (PaO2/FiO2 201-300 mm Hg), moderate (PaO2/FiO2 101-200 mmHg), and severe (PaO2/FiO2 ≤ 100). Volutrauma and barotrauma are thought to contribute to the development of ARDS and alter mortality. The damage that occurs to the lungs manifests itself as inflammation, which leads to poor gas exchange of oxygen and carbon dioxide. Several strategies of lung-protective mechanical ventilation have been investigated in ARDS, including the use of low tidal volume ventilation (LTVV) or ARDSNet strategy, high frequency oscillation ventilation (HFOV), and airway pressure release ventilation (APRV). Lung protective strategies may be best beneficial prior to the onset of the development of ARDS or early in the course of the disease. As a result of the ARDSNet trial, LTVV has been adopted as the usual standard of care of ventilation and safest mode of ventilation for patients with ARDS. Recently, APRV has been proposed as a potential alternative to LTVV. APRV is a form of ventilation that keeps the lungs inflated through the majority of the breath cycle and allows patients to breathe spontaneously above this level of inflation. APRV allows for spontaneous respiration with increased airway pressure, potentially allowing for decreased sedation, shorter duration of mechanical ventilation, and decreased need for vasopressors. APRV has been associated with possible reduction in incidence of ARDS and in-hospital mortality in non-randomized observational studies. In patients with established ARDS, the use of APRV has also not been well studied, with most studies limited to small observational studies often with no comparison group. One randomized trial using APRV alone had less than 30% of patients having a diagnosis of ARDS and did not show any difference in any outcomes. Recently, Zhou and colleagues conducted a randomized trial comparing APRV to conventional ventilation in 138 mechanically ventilated patients with mild to severe ARDS and found that APRV may shorten the duration of mechanical ventilation and reduce intensive care unit (ICU) length of stay. While some of these studies had shown promise of APRV compared to LTVV, there has not been acceptance of APRV into guidelines as first line ventilation, and recommendations of institutions such as the Canadian Agency for Drugs and Technology in Health (CADTH) recommends interpreting these results with caution. Consequently, there remains clinical equipoise on this issue. Some ICU clinicians will currently use APRV as a rescue mode of ventilation in ARDS in their clinical practice while others will continue with the use of LTVV. We would like to randomize patients to LTVV or APRV and examine the feasibility of conducting a large multicentre randomized controlled trial in Canada. Official Title ----------------- Early Use of Airway Pressure ReLease Ventilation in Critically Ill Adults With Moderate-to-severe Acute Respiratory Distress Syndrome Conditions ----------------- Acute Respiratory Distress Syndrome Intervention / Treatment ----------------- * Device: Low tidal volume ventilation * Device: Airway pressure release ventilation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Fulfilling the diagnostic criteria of ARDS, according to the Berlin definition Moderate to severe ARDS as defined as a PaO2: FiO2 ratio of ≤150 during invasive mechanical ventilation Endotracheal intubation and mechanical ventilation for ARDS less than 48 hours Exclusion Criteria: Age less than 18 years Pregnancy Intracranial hypertension (suspected or confirmed) Severe chronic obstructive pulmonary disease as defined by either: FEV1/FVC less than 50% predicted, or Chronic hypercarbia (PaCO2>45 mmHg), chronic hypoxemia (PaO2 < 55 mmHg) on room air, and/or elevated admission serum HCO3 >30 mmol/L Presence of documented barotrauma, i.e. pneumothorax Treatment with extracorporeal support (ECMO) at enrollment Refractory shock Advanced directives indicating preferences to not have advanced life support Moribund patient, i.e. not expected to survive longer than 24 hours Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Low tidal volume ventilation<br>Conventional low tidal volume ventilation | Device: Low tidal volume ventilation<br>* Conventional ventilation strategy for patient with ARDS<br>| | Experimental: Airway pressure release ventilation<br>Early use of airway pressure release ventilation | Device: Airway pressure release ventilation<br>* Experimental ventilation protocol for patients with ARDS<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Informed consent rate | A successful informed consent rate will be defined as ≥70% of substitute decision makers or patients approached choosing to participate in this trial | Informed consent rate will be measured over a 1 year period of the pilot study | | Recruitment rate | A successful recruitment rate will be achieving at least 15 patients over the 1 year period. | Recruitment rate will be measured over the one year of the pilot study. | | Protocol adherence rate | An adherence rate of at least 80% will be considered successful. | Protocol adherence will be measured for each study patient, and compiled over the duration of the pilot study (i.e. 1 year). | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | 28-day mortality | Death, measured from time of enrollment until 28 days. | Up to Day 28 | | In-hospital mortality | Death, at hospital discharge | Up to 365 days | | ICU length of stay | Length of stay in the intensive care unit | Up to 365 days | | Hospital length of stay | Length of stay in the hospital in days | Up to 365 days | | Length/duration of mechanical ventilation | Length of time patient was on mechanical ventilation | Up to 365 days | | Incidence of tracheostomy | Incidence of tracheostomy during their ICU stay | Up to 365 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Airway pressure release ventilation, low tidal volume ventilation, APRV, ARDSNet ventilation, LTVV, acute respiratory distress syndrome, ARDS

NCT04149210

FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial

This study aims :~To assess the efficacy of fluorometholone 0.1% one drop twice daily for four weeks in reducing the incidence of post-operative trachomatous trichiasis (TT) when given as adjunctive therapy with TT surgery in the programmatic setting~To assess whether such treatment is sufficiently safe for wide-scale implementation in TT programs.~To estimate the costs of adding fluorometholone 0.1% treatment to TT surgery per case of postoperative TT averted, and to characterize the value of such treatment under a range of plausible health economic circumstances

The investigators are pursuing an agenda to evaluate a new potentially cost-effective approach to improving trichiasis surgery outcomes: perioperative topical anti-inflammatory therapy. Inflammation-whether induced by the trachoma disease process or surgery itself-most likely contributes to progressive cicatrization leading to failure of lid rotation surgery in a clinically important proportion of TT cases. The investigators hypothesize that adjunctive topical fluorometholone therapy following trichiasis surgery will reduce the risk of recurrent trichiasis and will be acceptably safe. The rationale for the efficacy aspect of this hypothesis is that interruption of inflammation postoperatively would reduce postoperative scarring/contracture driven by ongoing disease-driven inflammation and/or surgically-induced inflammation thus reducing the incidence of TT recurrence (post-operative TT) and other inflammation-related outcomes.

FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial

Trachomatous Trichiasis (TT), Eye Diseases, Eyelid Diseases, Trachomatous, Trichiasis

* Drug: Fluorometholone 0.1% Oph Susp * Drug: Artificial Tears

Inclusion Criteria:~Age 15 years or more, corresponding to the age of patients treated in the Fred Hollows Foundation/Federal Ministry of Health Program at field sites without general anesthesia.~One or both eyes with upper lid trachomatous trichiasis-with one or more eyelashes touching the eye or evidence of epilation, with a plan to undergo TT surgery on at least one upper eyelid.~Collection of all baseline data prior to randomization~Signed, informed consent (and assent, when applicable)~Exclusion Criteria:~Contraindication(s) to the use of the test articles, including a known allergy or sensitivity to the study medication (fluorometholone) or its components, and contraindication(s) to use of azithromycin~IOP≥22 mmHg and/or currently taking more than two ocular anti-hypertensive medications in the study eye (prior IOP-lowering surgery is acceptable; combinations of two IOP-lowering agents such as Dorzamol are considered two medications)~A known severe / serious ocular pathology or medical condition which may preclude study completion or increase the risk of harm in the study (e.g., suspicion of non-trachomatous active ocular infection or suspicion of glaucoma of a degree to which where an intraocular pressure spike would be vision-threatening).~Any condition known to be present at baseline for which it is anticipated ocular or systemic corticosteroid therapy will be required.~Any significant illness or condition (e.g., hypertension with systolic blood pressure≥170 mmHg and/or diastolic blood pressure≥110 mmHg) that could, in the study team's opinion, be expected to interfere with the study parameters or study conduct; or put the subject at significant risk.~Previous upper lid TT surgery on all eyes with upper lid TT. (If one eye has previously undergone upper lid TT surgery but another eye with upper lid TT has not, the patient may be enrolled, and only the latter eye will be counted for the primary analyses).

15 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: This is a 1:1 randomized, double-masked, placebo controlled clinical trial Masking: Triple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of postoperative TT by one year, as determined by trained study team members | The primary outcome measure is the postoperative recurrence of trachomatous trichiasis (TT), defined as one or more eyelashes touching the globe or evidence of epilation (lash stubs) on examination, or a history of repeat trichiasis surgery at any time during the one year follow-up period after the baseline surgery. | 12 months |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Efficacy Measure 1 - Entropion | Entropion (presence and extent) | 1 year | | Efficacy Measure 2 - Reoperation | Reoperation for postoperative TT (recommended or done) | 1 year | | Efficacy Measure 3 - Lashes | Number and location of lashes touching the globe | 1 year | | Safety/adverse outcomes 1 - Corneal Opacity | Corneal opacity (change in proportion from baseline) | 1 year | | Safety/adverse outcomes 2 - Overcorrection | Overcorrection - The surgery rotates the eyelid away from the eyeball (the disease consists of inturning of the eyelid such that the lashes touch the eyeball). Overcorrection would be rotating it away from the globe. | 1 year | | Safety/adverse outcomes 3 - Eyelid Abnormalities | Eyelid notching/eyelid contour abnormalities | 1 year | | Safety/adverse outcome 4 - Lid Closure Defect | Lid closure defect | 1 year | | Safety/adverse outcomes 5 - Granuloma | Granuloma | 1 year | | Safety/adverse outcomes 7 - IOP in mmHg | IOP elevation | 4 weeks | | Safety/adverse outcomes 8 - Cataract Surgery | Occurrence of cataract surgery | 1 year | | Safety/adverse outcomes - Adverse Events | Adverse events attributed to study treatment | 1 year | | Additional variables 1 - Visual Acuity | Visual acuity with presenting correction | 1 year |

fluorometholone 0.1%, trachomatous trichiasis, Eye Diseases, Eyelid Diseases, trachomatous, trichiasis, FLAME, TT Surgery

Fluorometholone, Lubricant Eye Drops, Ophthalmic Solutions, Pharmaceutical Solutions, Anti-Inflammatory Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Anti-Allergic Agents

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: fluorometholone<br>Fluorometholone 0.1% eyedrops, one drop twice daily for four weeks | Drug: Fluorometholone 0.1% Oph Susp<br>* fluorometholone 0.1% one drop twice daily for four weeks, beginning with one drop just before trachomatous trichiasis surgery on the upper lid.<br>* Other names: FML;| | Placebo Comparator: Artificial Tears<br>one drop two times daily for four weeks | Drug: Artificial Tears<br>* Artificial tears (placebo) given one drop twice daily for four weeks, beginning with one drop just prior to trachomatous trichiasis surgery on the upper lid.<br>* Other names: Placebo;|

FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial Study Overview ================= Brief Summary ----------------- This study aims : To assess the efficacy of fluorometholone 0.1% one drop twice daily for four weeks in reducing the incidence of post-operative trachomatous trichiasis (TT) when given as adjunctive therapy with TT surgery in the programmatic setting To assess whether such treatment is sufficiently safe for wide-scale implementation in TT programs. To estimate the costs of adding fluorometholone 0.1% treatment to TT surgery per case of postoperative TT averted, and to characterize the value of such treatment under a range of plausible health economic circumstances Detailed Description ----------------- The investigators are pursuing an agenda to evaluate a new potentially cost-effective approach to improving trichiasis surgery outcomes: perioperative topical anti-inflammatory therapy. Inflammation-whether induced by the trachoma disease process or surgery itself-most likely contributes to progressive cicatrization leading to failure of lid rotation surgery in a clinically important proportion of TT cases. The investigators hypothesize that adjunctive topical fluorometholone therapy following trichiasis surgery will reduce the risk of recurrent trichiasis and will be acceptably safe. The rationale for the efficacy aspect of this hypothesis is that interruption of inflammation postoperatively would reduce postoperative scarring/contracture driven by ongoing disease-driven inflammation and/or surgically-induced inflammation thus reducing the incidence of TT recurrence (post-operative TT) and other inflammation-related outcomes. Official Title ----------------- FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial Conditions ----------------- Trachomatous Trichiasis (TT), Eye Diseases, Eyelid Diseases, Trachomatous, Trichiasis Intervention / Treatment ----------------- * Drug: Fluorometholone 0.1% Oph Susp * Drug: Artificial Tears Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 15 years or more, corresponding to the age of patients treated in the Fred Hollows Foundation/Federal Ministry of Health Program at field sites without general anesthesia. One or both eyes with upper lid trachomatous trichiasis-with one or more eyelashes touching the eye or evidence of epilation, with a plan to undergo TT surgery on at least one upper eyelid. Collection of all baseline data prior to randomization Signed, informed consent (and assent, when applicable) Exclusion Criteria: Contraindication(s) to the use of the test articles, including a known allergy or sensitivity to the study medication (fluorometholone) or its components, and contraindication(s) to use of azithromycin IOP≥22 mmHg and/or currently taking more than two ocular anti-hypertensive medications in the study eye (prior IOP-lowering surgery is acceptable; combinations of two IOP-lowering agents such as Dorzamol are considered two medications) A known severe / serious ocular pathology or medical condition which may preclude study completion or increase the risk of harm in the study (e.g., suspicion of non-trachomatous active ocular infection or suspicion of glaucoma of a degree to which where an intraocular pressure spike would be vision-threatening). Any condition known to be present at baseline for which it is anticipated ocular or systemic corticosteroid therapy will be required. Any significant illness or condition (e.g., hypertension with systolic blood pressure≥170 mmHg and/or diastolic blood pressure≥110 mmHg) that could, in the study team's opinion, be expected to interfere with the study parameters or study conduct; or put the subject at significant risk. Previous upper lid TT surgery on all eyes with upper lid TT. (If one eye has previously undergone upper lid TT surgery but another eye with upper lid TT has not, the patient may be enrolled, and only the latter eye will be counted for the primary analyses). Ages Eligible for Study ----------------- Minimum Age: 15 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: This is a 1:1 randomized, double-masked, placebo controlled clinical trial Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: fluorometholone<br>Fluorometholone 0.1% eyedrops, one drop twice daily for four weeks | Drug: Fluorometholone 0.1% Oph Susp<br>* fluorometholone 0.1% one drop twice daily for four weeks, beginning with one drop just before trachomatous trichiasis surgery on the upper lid.<br>* Other names: FML;| | Placebo Comparator: Artificial Tears<br>one drop two times daily for four weeks | Drug: Artificial Tears<br>* Artificial tears (placebo) given one drop twice daily for four weeks, beginning with one drop just prior to trachomatous trichiasis surgery on the upper lid.<br>* Other names: Placebo;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of postoperative TT by one year, as determined by trained study team members | The primary outcome measure is the postoperative recurrence of trachomatous trichiasis (TT), defined as one or more eyelashes touching the globe or evidence of epilation (lash stubs) on examination, or a history of repeat trichiasis surgery at any time during the one year follow-up period after the baseline surgery. | 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Efficacy Measure 1 - Entropion | Entropion (presence and extent) | 1 year | | Efficacy Measure 2 - Reoperation | Reoperation for postoperative TT (recommended or done) | 1 year | | Efficacy Measure 3 - Lashes | Number and location of lashes touching the globe | 1 year | | Safety/adverse outcomes 1 - Corneal Opacity | Corneal opacity (change in proportion from baseline) | 1 year | | Safety/adverse outcomes 2 - Overcorrection | Overcorrection - The surgery rotates the eyelid away from the eyeball (the disease consists of inturning of the eyelid such that the lashes touch the eyeball). Overcorrection would be rotating it away from the globe. | 1 year | | Safety/adverse outcomes 3 - Eyelid Abnormalities | Eyelid notching/eyelid contour abnormalities | 1 year | | Safety/adverse outcome 4 - Lid Closure Defect | Lid closure defect | 1 year | | Safety/adverse outcomes 5 - Granuloma | Granuloma | 1 year | | Safety/adverse outcomes 7 - IOP in mmHg | IOP elevation | 4 weeks | | Safety/adverse outcomes 8 - Cataract Surgery | Occurrence of cataract surgery | 1 year | | Safety/adverse outcomes - Adverse Events | Adverse events attributed to study treatment | 1 year | | Additional variables 1 - Visual Acuity | Visual acuity with presenting correction | 1 year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- fluorometholone 0.1%, trachomatous trichiasis, Eye Diseases, Eyelid Diseases, trachomatous, trichiasis, FLAME, TT Surgery

NCT02145260

Trial of Dialysate Sodium in Chronic Hospitalized Hemodialysis Patients

Intra-dialytic hypotensive (IDH) events can be defined as an abrupt decline in blood pressure that cause symptoms and/or require an intervention. They are common, affecting up to one third of maintenance HD sessions. Detrimental associations include: development of myocardial stunning, cerebral hypo-perfusion, vascular access thrombosis and greater mortality.~Rapid solute removal by HD generates temporary osmotic gradients between the intra-vascular and intra-cellular compartments, promoting trans-cellular fluid movement and resultant hypotension. Manipulation of osmotic gradients, e.g. using higher dialysate sodium (DNa), may ameliorate excess SBP decline during HD.~This study aims to assess the effects of higher (142 mmol/L) versus lower (138 mmol/L) dialysate sodium (DNa) use in adult chronic hemodialysis patients admitted to hospital on intra-dialytic blood pressure and biomarkers of cardiac ischemia.~The investigators will randomly assign subjects to higher versus lower DNa during their hospital stay, up to a maximum of six HD sessions.

Randomized Trial of Dialysate Sodium in Chronic Hospitalized Hemodialysis Patients

Intra-dialytic Hypotension

* Drug: Lower dialysate sodium (138 mmol/L; using Renasol hemodialysis concentrate) * Drug: Higher dialysate sodium (142 mmol/L; using Renasol hemodialysis concentrate)

Inclusion Criteria:~Chronic HD (>90 days)~Age ≥18y~Informed consent~First admission during study period.~Exclusion Criteria:~Use of pressors~Pre-dialysis serum sodium <=128mmol/L or > 145 mmol/L~Pre-dialysis SBP >180 mmHg~Intensive care stay earlier in admission~Expected length of stay <24 hours (e.g. admission for HD access procedure)~Acute coronary syndrome within seven days~Acute stroke~Institutionalized individuals~Pregnancy

18 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Intra-dialytic Decline in Systolic Blood Pressure | Pre-dialysis SBP minus lowest intra-dialytic SBP. The data table reflect the change in systolic blood pressured (SBP) assessed at up to 6 HD sessions, where the change for each session was calculated as the pre-SBP minus the lowest SBP (during the session), and the change values from the multiple sessions were then averaged for a participant. | Average decline in systolic blood pressure will be measured up to a maximum of six inpatient HD sessions, occurring over a two-week time period |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Pre-dialysis High-sensitivity Troponin I | Cardiac injury biomarkers | The change in pre-dialysis high sensitivity troponin I concentrations will be measured between the first and second inpatient hemodialysis sessions, occuring over a period of three days |

Hemodialysis, Hypotension, Hospitalization

Dialysis Solutions, Pharmaceutical Solutions

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Lower dialysate sodium<br>Dialysate sodium concentration of 138 mmol/L | Drug: Lower dialysate sodium (138 mmol/L; using Renasol hemodialysis concentrate)<br>* A lower dialysate sodium will bes used in the active comparator arm (138 mmol/L)<br>| | Experimental: Higher dialysate sodium<br>Dialysate sodium concentration of 142 mmol/L | Drug: Higher dialysate sodium (142 mmol/L; using Renasol hemodialysis concentrate)<br>* A higher dialysate sodium will be used in the experimental arm (142 mmol/L)<br>|

Trial of Dialysate Sodium in Chronic Hospitalized Hemodialysis Patients Study Overview ================= Brief Summary ----------------- Intra-dialytic hypotensive (IDH) events can be defined as an abrupt decline in blood pressure that cause symptoms and/or require an intervention. They are common, affecting up to one third of maintenance HD sessions. Detrimental associations include: development of myocardial stunning, cerebral hypo-perfusion, vascular access thrombosis and greater mortality. Rapid solute removal by HD generates temporary osmotic gradients between the intra-vascular and intra-cellular compartments, promoting trans-cellular fluid movement and resultant hypotension. Manipulation of osmotic gradients, e.g. using higher dialysate sodium (DNa), may ameliorate excess SBP decline during HD. This study aims to assess the effects of higher (142 mmol/L) versus lower (138 mmol/L) dialysate sodium (DNa) use in adult chronic hemodialysis patients admitted to hospital on intra-dialytic blood pressure and biomarkers of cardiac ischemia. The investigators will randomly assign subjects to higher versus lower DNa during their hospital stay, up to a maximum of six HD sessions. Official Title ----------------- Randomized Trial of Dialysate Sodium in Chronic Hospitalized Hemodialysis Patients Conditions ----------------- Intra-dialytic Hypotension Intervention / Treatment ----------------- * Drug: Lower dialysate sodium (138 mmol/L; using Renasol hemodialysis concentrate) * Drug: Higher dialysate sodium (142 mmol/L; using Renasol hemodialysis concentrate) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Chronic HD (>90 days) Age ≥18y Informed consent First admission during study period. Exclusion Criteria: Use of pressors Pre-dialysis serum sodium <=128mmol/L or > 145 mmol/L Pre-dialysis SBP >180 mmHg Intensive care stay earlier in admission Expected length of stay <24 hours (e.g. admission for HD access procedure) Acute coronary syndrome within seven days Acute stroke Institutionalized individuals Pregnancy Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Lower dialysate sodium<br>Dialysate sodium concentration of 138 mmol/L | Drug: Lower dialysate sodium (138 mmol/L; using Renasol hemodialysis concentrate)<br>* A lower dialysate sodium will bes used in the active comparator arm (138 mmol/L)<br>| | Experimental: Higher dialysate sodium<br>Dialysate sodium concentration of 142 mmol/L | Drug: Higher dialysate sodium (142 mmol/L; using Renasol hemodialysis concentrate)<br>* A higher dialysate sodium will be used in the experimental arm (142 mmol/L)<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Intra-dialytic Decline in Systolic Blood Pressure | Pre-dialysis SBP minus lowest intra-dialytic SBP. The data table reflect the change in systolic blood pressured (SBP) assessed at up to 6 HD sessions, where the change for each session was calculated as the pre-SBP minus the lowest SBP (during the session), and the change values from the multiple sessions were then averaged for a participant. | Average decline in systolic blood pressure will be measured up to a maximum of six inpatient HD sessions, occurring over a two-week time period | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Pre-dialysis High-sensitivity Troponin I | Cardiac injury biomarkers | The change in pre-dialysis high sensitivity troponin I concentrations will be measured between the first and second inpatient hemodialysis sessions, occuring over a period of three days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Hemodialysis, Hypotension, Hospitalization

NCT04535856

Therapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients

This is a phase 1 clinical trial to verify the safety and efficacy of DW-MSC in COVID-19 patients. A total of 9 subjects are randomly allocated. Subjects who meet the final inclusion and exclusion criteria are randomized to the test groups (low-dose group and high-dose group) or control group (placebo group) in a ratio of 1:1:1. Subjects assigned to the test groups were administered intravenously once with 5 x 10^7cells of DW-MSC for the low-dose group or 1 x 10^8cells for the high-dose group after registration. Subjects assigned to the control group were administered with placebo in the same manner as the test drug (DW-MSC). At this time, all of the existing standard co-treatment are allowed. DW-MSC is adjunct therapy to standard therapy.~This clinical trial is a double-blind trial, in which a randomized method will be used. To maintain the double-blindness of the study, statistician who do not participate in this study independently generate randomization code. Subjects will be randomized to the test groups (low-dose group and high-dose group) or the control group (placebo group) in a 1:1:1 ratio. After the completion of the trial, the randomization code will be disclosed after unlocking the database and unblinding procedures. Follow Up period: observed for 28 days after a single administration

Patients with Covid-19 have a mortality rate of about 35 ~ 50% and currently, severe patients caused by the Coronavirus show respiratory distress. To date, the incidence rate has been more than 3 million each year; however, as the increase and globalization of the environmental pollution has been expanded, the number of patients is expected to increase due to acute diseases such as the Middle East Respiratory virus, SARS, and coronavirus.~Since 2015, Daewoong Pharmaceutical intends to use stem cells for product research on rare and intractable diseases including respiratory distress. Stem cells are also called pluripotent cells or truncal cells that can convert to any organ. It is an embryonic stage undifferentiated cell that has stopped differentiating before forming a specific organ whose differentiation has not been determined and has the ability to differentiate into muscle, bone, and internal conformal body organs. There are three types of stem cells: embryonic stem cells, adult stem cells, and induced pluripotent stem cells. Daewoong Pharmaceutical intends to develop cell therapy products using mesenchymal stem cells (MSC).

Therapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients: Randomized, Double-blind, and Placebo-controlled

Covid19, Corona Virus Infection, SAR

* Drug: allogeneic mesenchymal stem cell * Other: Placebo

Inclusion Criteria:~Age of 19 years or older at the time of screening~Those who have been confirmed COVID-19 infection through PCR test~Patients with mild or moderate COVID-19 who meet National EWS (0~6)~Those who have given written consent and voluntarily decided to participate before the screening procedure after understanding the detailed description of the clinical trial.~Those who are suitable as subjects for this clinical study when judged by physical examination, clinical laboratory test, and other medical examination as stated in the flowchart of protocol.~Exclusion Criteria:~Those who have history of hypersensitivity to the components of the investigational product or the reference product~Those with viral or bacterial pneumonia other than expected indications~Patients receiving organ transplants within 6 months of screening~Patients with a history of pulmonary embolism~Patients who have indications of investigational products as an underlying disease (ex. HIV patients in the clinical study of antiretroviral drugs)~Patients who are pregnant or lactating~Those who are determined by the investigator to be unsuitable for participation in the clinical trial due to other reasons including the results of the clinical laboratory test.~Patients participating in other clinical studies

19 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Randomized, Double-blind, and Placebo-controlled Clinical Trial Masking: Quadruple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of TEAE* in Treatment group | Incidence of TEAE* in Treatment group~* TEAE: Treatment-Emergent Adverse Event All adverse reactions will be organized according to System Organ Class (SOC) and Preferred Term (PT) using MedDRA (Medical Dictionary for Regulatory Activities), and the incidence of treatment-emergent adverse events will be summarized for the coded adverse reactions. | 28 days |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Survival rate | Survival rate is defined as the rate of subjects surviving until Day 14 and Day 28, and the number and rate of surviving subjects for each administration group is given. | until Day 14 and Day 28 | | Duration of hospitalization | Duration of hospitalization is defined as the number of days in the hospital until Day 28, and descriptive statistics (number of subjects, mean, standard deviation, median, minimum, maximum) are given for each administration group. | 28 days | | Clinical improvement Ordinal scale | Clinical improvement measured by Ordinal scale change for clinical improvement from baseline to Day 14 and 28 | from baseline to Day 14 and Day 28 | | Clinical improvement National EWS | Clinical improvement measured by National EWS (National Early Warning Score) change from baseline to Day 7, 14, 28.~EWS Points, Risk and Interpretation as follows:~0~4: Low clinical risk; interpretation= Ward-based response 3~4 : Low~medium clinical risk; interpretation= Urgent ward-based response 5~6: Medium clinical risk; interpretation= Key threshold for urgent response | from baseline to Day 7, 14 and Day 28 | | Clinical improvement Oxygenation index | Clinical improvement measured by Oxygenation index (PaO2/FiO2) change from baseline (Day 1, 3, 7, 10, 14, 28) | Day 1, 3, 7, 10, 14, 28 | | Clinical improvement Lung involvement change | Clinical improvement measured by Lung involvement change by Imaging from baseline (Day 7, 14, 28) | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for WBC | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for Lymphocytes | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for ESR | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for CRP | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for Fibrinogen | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for IL-6, TNF-α, IL-1β, IF-γ (Day 7, 14, 28) | Day 7, 14, 28 |

Infectious Disease, covid-19, allogeneic mesenchymal stem cell

Coronavirus Infections, Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Infections, Virus Diseases, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases, COVID-19

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Low-dose group<br>Low-dose group (5 x 10^7cells):~Drug substance and the amount: 2.5 × 107 cells/1 mL/vial, 2 vials for low-dose group | Drug: allogeneic mesenchymal stem cell<br>* Assignment of Administration Group allogeneic mesenchymal stem cell:~Low-dose group (5 x 10^7cells)~High-dose group (1 x 10^8 cells)<br>* Other names: Investigational product;| | Experimental: High-dose group<br>High-dose group (1 x 10^8 cells):~Drug substance and the amount: 2.5 × 107 cells/1 mL/vial, 4 vials for High-dose group | Drug: allogeneic mesenchymal stem cell<br>* Assignment of Administration Group allogeneic mesenchymal stem cell:~Low-dose group (5 x 10^7cells)~High-dose group (1 x 10^8 cells)<br>* Other names: Investigational product;| | Placebo Comparator: Control group (placebo)<br>Control group (placebo):~No Drug substance: 4 vials for Place group | Other: Placebo<br>* Control group (placebo)<br>|

Therapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients Study Overview ================= Brief Summary ----------------- This is a phase 1 clinical trial to verify the safety and efficacy of DW-MSC in COVID-19 patients. A total of 9 subjects are randomly allocated. Subjects who meet the final inclusion and exclusion criteria are randomized to the test groups (low-dose group and high-dose group) or control group (placebo group) in a ratio of 1:1:1. Subjects assigned to the test groups were administered intravenously once with 5 x 10^7cells of DW-MSC for the low-dose group or 1 x 10^8cells for the high-dose group after registration. Subjects assigned to the control group were administered with placebo in the same manner as the test drug (DW-MSC). At this time, all of the existing standard co-treatment are allowed. DW-MSC is adjunct therapy to standard therapy. This clinical trial is a double-blind trial, in which a randomized method will be used. To maintain the double-blindness of the study, statistician who do not participate in this study independently generate randomization code. Subjects will be randomized to the test groups (low-dose group and high-dose group) or the control group (placebo group) in a 1:1:1 ratio. After the completion of the trial, the randomization code will be disclosed after unlocking the database and unblinding procedures. Follow Up period: observed for 28 days after a single administration Detailed Description ----------------- Patients with Covid-19 have a mortality rate of about 35 50% and currently, severe patients caused by the Coronavirus show respiratory distress. To date, the incidence rate has been more than 3 million each year; however, as the increase and globalization of the environmental pollution has been expanded, the number of patients is expected to increase due to acute diseases such as the Middle East Respiratory virus, SARS, and coronavirus. Since 2015, Daewoong Pharmaceutical intends to use stem cells for product research on rare and intractable diseases including respiratory distress. Stem cells are also called pluripotent cells or truncal cells that can convert to any organ. It is an embryonic stage undifferentiated cell that has stopped differentiating before forming a specific organ whose differentiation has not been determined and has the ability to differentiate into muscle, bone, and internal conformal body organs. There are three types of stem cells: embryonic stem cells, adult stem cells, and induced pluripotent stem cells. Daewoong Pharmaceutical intends to develop cell therapy products using mesenchymal stem cells (MSC). Official Title ----------------- Therapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients: Randomized, Double-blind, and Placebo-controlled Conditions ----------------- Covid19, Corona Virus Infection, SAR Intervention / Treatment ----------------- * Drug: allogeneic mesenchymal stem cell * Other: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age of 19 years or older at the time of screening Those who have been confirmed COVID-19 infection through PCR test Patients with mild or moderate COVID-19 who meet National EWS (0 6) Those who have given written consent and voluntarily decided to participate before the screening procedure after understanding the detailed description of the clinical trial. Those who are suitable as subjects for this clinical study when judged by physical examination, clinical laboratory test, and other medical examination as stated in the flowchart of protocol. Exclusion Criteria: Those who have history of hypersensitivity to the components of the investigational product or the reference product Those with viral or bacterial pneumonia other than expected indications Patients receiving organ transplants within 6 months of screening Patients with a history of pulmonary embolism Patients who have indications of investigational products as an underlying disease (ex. HIV patients in the clinical study of antiretroviral drugs) Patients who are pregnant or lactating Those who are determined by the investigator to be unsuitable for participation in the clinical trial due to other reasons including the results of the clinical laboratory test. Patients participating in other clinical studies Ages Eligible for Study ----------------- Minimum Age: 19 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Randomized, Double-blind, and Placebo-controlled Clinical Trial Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Low-dose group<br>Low-dose group (5 x 10^7cells): Drug substance and the amount: 2.5 × 107 cells/1 mL/vial, 2 vials for low-dose group | Drug: allogeneic mesenchymal stem cell<br>* Assignment of Administration Group allogeneic mesenchymal stem cell: Low-dose group (5 x 10^7cells) High-dose group (1 x 10^8 cells)<br>* Other names: Investigational product;| | Experimental: High-dose group<br>High-dose group (1 x 10^8 cells): Drug substance and the amount: 2.5 × 107 cells/1 mL/vial, 4 vials for High-dose group | Drug: allogeneic mesenchymal stem cell<br>* Assignment of Administration Group allogeneic mesenchymal stem cell: Low-dose group (5 x 10^7cells) High-dose group (1 x 10^8 cells)<br>* Other names: Investigational product;| | Placebo Comparator: Control group (placebo)<br>Control group (placebo): No Drug substance: 4 vials for Place group | Other: Placebo<br>* Control group (placebo)<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of TEAE* in Treatment group | Incidence of TEAE* in Treatment group * TEAE: Treatment-Emergent Adverse Event All adverse reactions will be organized according to System Organ Class (SOC) and Preferred Term (PT) using MedDRA (Medical Dictionary for Regulatory Activities), and the incidence of treatment-emergent adverse events will be summarized for the coded adverse reactions. | 28 days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Survival rate | Survival rate is defined as the rate of subjects surviving until Day 14 and Day 28, and the number and rate of surviving subjects for each administration group is given. | until Day 14 and Day 28 | | Duration of hospitalization | Duration of hospitalization is defined as the number of days in the hospital until Day 28, and descriptive statistics (number of subjects, mean, standard deviation, median, minimum, maximum) are given for each administration group. | 28 days | | Clinical improvement Ordinal scale | Clinical improvement measured by Ordinal scale change for clinical improvement from baseline to Day 14 and 28 | from baseline to Day 14 and Day 28 | | Clinical improvement National EWS | Clinical improvement measured by National EWS (National Early Warning Score) change from baseline to Day 7, 14, 28. EWS Points, Risk and Interpretation as follows: 0 4: Low clinical risk; interpretation= Ward-based response 3 4 : Low medium clinical risk; interpretation= Urgent ward-based response 5 6: Medium clinical risk; interpretation= Key threshold for urgent response | from baseline to Day 7, 14 and Day 28 | | Clinical improvement Oxygenation index | Clinical improvement measured by Oxygenation index (PaO2/FiO2) change from baseline (Day 1, 3, 7, 10, 14, 28) | Day 1, 3, 7, 10, 14, 28 | | Clinical improvement Lung involvement change | Clinical improvement measured by Lung involvement change by Imaging from baseline (Day 7, 14, 28) | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for WBC | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for Lymphocytes | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for ESR | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for CRP | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for Fibrinogen | Day 7, 14, 28 | | Clinical improvement Inflammation markers change | Inflammation markers change from baseline for IL-6, TNF-α, IL-1β, IF-γ (Day 7, 14, 28) | Day 7, 14, 28 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Infectious Disease, covid-19, allogeneic mesenchymal stem cell

NCT01654328

Oral Versus Intravenous Hydration to Prevent Contrast Induced Nephropathy

The purpose of this study is to investigate if home-hydration is a non inferior alternative for in-hospital hydration in the prevention of Contrast Induced Nephropathy in high risk patients.

Rationale: Iodinated contrast media are regularly used in diagnostic and interventional procedures. The intravascular use of these contrast media can cause acute kidney injury (Contrast Induced Nephropathy). Contrast Induced Nephropathy is associated with increased morbidity and mortality. There are no treatment options, therefore preventive measures should be taken. Volume expansion reduces the risk of Contrast Induced Nephropathy. Current guidelines for the prevention of Contrast-Induced Nephropathy advise that high risk patients be admitted for hydration with intravenous normal saline for a period of 8-24 hours. This proposal evaluates an alternative method of hydration; home hydration with salt tablets.~Objective: To investigate if home-hydration is a non inferior alternative for in-hospital hydration in the prevention of Contrast Induced Nephropathy in high risk patients.~Study design: multi-centre randomized controlled trial.~Study population: Adult patients > 18 years undergoing an elective procedure involving intravascular administration of iodinated contrast media and at high risk for the development of Contrast Induced Nephropathy (as defined by guideline criteria).~Intervention: Arm A: sodium chloride 1g/10kg of body weight/day per os on day -2 and -1 before contrast exposure. With a maximum dose of 10 gram sodium chloride a day.~Arm B: Nacl 0.9% total 1000ml in 4 hrs or (in case of heart failure or severe renal failure) 12 hrs before and in 4 or in 12 hrs after contrast administration.~Main study parameters/endpoints: The incidence of Contrast Induced Nephropathy, effect on the need for hospitalisation, patient satisfaction.~Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients who are randomized for home hydration will receive salt tablets and start 48 hrs before the procedure. The risk of taking salt tablets is low, there are some reports of nausea. Because the investigators exclude patients who have decompensated heart failure the use of these amounts of salt is considered safe and the investigators do not expect signs of overhydration. The investigators monitor this by a telephone consult, 24 hours after the intake of the first tablets. Body weight and intake of tablets will be monitored. Before contrast administration a blood and urine sample will be taken.~Patients who are randomized for intravenous hydration will be admitted and will receive standard treatment for high risk patients with the addition of one blood and urine sample taken before contrast administration.~In all patients 48-72 hours after contrast administration a blood sample is taken to check for the development of CIN, this is standard treatment according to the guidelines.~The investigators will ask all patients to fill in a questionnaire on patient satisfaction.

Oral Versus Intravenous Hydration to Prevent Contrast Induced Nephropathy

Radiographic Contrast Agent Nephropathy

* Drug: Sodium chloride tablets * Drug: Isotonic saline intravenously

Inclusion Criteria:~Adult patients > 18 years undergoing an elective procedure involving intravascular administration of iodinated contrast media~high risk for the development of Contrast Induced Nephropathy (as defined by guideline criteria~Exclusion Criteria:~Age < 18.~Low risk for the development of CIN, therefore no need for hydration~Emergency contrast procedure.~Overt signs of overhydration; orthopnea or pulmonal rales at the time of the first consult.~Double or triple diuretic use for pre-existing heart failure. Severe heart failure, in which case salt load is not safe (physician decision) Severe renal failure (CKD stage V eGFR < 15ml/min/1.73m2) Multiple Myeloma. Repeated contrast exposure < 2 weeks Unstable serum creatinine > 25% change < 6 weeks The inability to provide written informed consent. Participation in another intervention study

18 Years

All

No

Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The primary endpoint will be change in the creatinine concentration between the 48-72 hours creatinine levels and the baseline levels, expressed as ratio. | | 48-72 hours after contrast administration |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | we will evaluate the incidence of contrast nephropathy in the groups defined as a rise in serum creatinine of ≥25% or ≥44umol/L 48-72 hours after contrast administration | | 48-72 hours after contrast administration | | patient satisfaction. | patient satisfacation will be evaluated using a questionnaire | up to 1 week after intervention | | the incidence of adverse events | | up to 1 week after intervention |

contrast media, kidney injury, hydration

Kidney Diseases, Urologic Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Arm A: sodium chloride tablets<br>Arm A: sodium chloride 1g/10kg of body weight /day per os on day -2 and -1 before contrast exposure. With a maximum dose of 10 gram sodium chloride a day. | Drug: Sodium chloride tablets<br>* sodium chloride 1g/10kg of body weight /day per os on day -2 and -1 before contrast exposure. With a maximum dose of 10 gram sodium chloride a day.<br>| | Active Comparator: B: isotonic saline intravenously<br>Sodium chloride solution (isotonic saline (NaCl 0.9%) total 1000ml in 4 hrs or (in case of heart failure or severe renal failure) 12 hrs before and in 4 or in 12 hrs after contrast administration. | Drug: Isotonic saline intravenously<br>* isotonic saline (Nacl 0.9%) total 1000ml in 4 hrs or (in case of heart failure or severe renal failure) 12 hrs before and in 4 or in 12 hrs after contrast administration.<br>|

Oral Versus Intravenous Hydration to Prevent Contrast Induced Nephropathy Study Overview ================= Brief Summary ----------------- The purpose of this study is to investigate if home-hydration is a non inferior alternative for in-hospital hydration in the prevention of Contrast Induced Nephropathy in high risk patients. Detailed Description ----------------- Rationale: Iodinated contrast media are regularly used in diagnostic and interventional procedures. The intravascular use of these contrast media can cause acute kidney injury (Contrast Induced Nephropathy). Contrast Induced Nephropathy is associated with increased morbidity and mortality. There are no treatment options, therefore preventive measures should be taken. Volume expansion reduces the risk of Contrast Induced Nephropathy. Current guidelines for the prevention of Contrast-Induced Nephropathy advise that high risk patients be admitted for hydration with intravenous normal saline for a period of 8-24 hours. This proposal evaluates an alternative method of hydration; home hydration with salt tablets. Objective: To investigate if home-hydration is a non inferior alternative for in-hospital hydration in the prevention of Contrast Induced Nephropathy in high risk patients. Study design: multi-centre randomized controlled trial. Study population: Adult patients > 18 years undergoing an elective procedure involving intravascular administration of iodinated contrast media and at high risk for the development of Contrast Induced Nephropathy (as defined by guideline criteria). Intervention: Arm A: sodium chloride 1g/10kg of body weight/day per os on day -2 and -1 before contrast exposure. With a maximum dose of 10 gram sodium chloride a day. Arm B: Nacl 0.9% total 1000ml in 4 hrs or (in case of heart failure or severe renal failure) 12 hrs before and in 4 or in 12 hrs after contrast administration. Main study parameters/endpoints: The incidence of Contrast Induced Nephropathy, effect on the need for hospitalisation, patient satisfaction. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients who are randomized for home hydration will receive salt tablets and start 48 hrs before the procedure. The risk of taking salt tablets is low, there are some reports of nausea. Because the investigators exclude patients who have decompensated heart failure the use of these amounts of salt is considered safe and the investigators do not expect signs of overhydration. The investigators monitor this by a telephone consult, 24 hours after the intake of the first tablets. Body weight and intake of tablets will be monitored. Before contrast administration a blood and urine sample will be taken. Patients who are randomized for intravenous hydration will be admitted and will receive standard treatment for high risk patients with the addition of one blood and urine sample taken before contrast administration. In all patients 48-72 hours after contrast administration a blood sample is taken to check for the development of CIN, this is standard treatment according to the guidelines. The investigators will ask all patients to fill in a questionnaire on patient satisfaction. Official Title ----------------- Oral Versus Intravenous Hydration to Prevent Contrast Induced Nephropathy Conditions ----------------- Radiographic Contrast Agent Nephropathy Intervention / Treatment ----------------- * Drug: Sodium chloride tablets * Drug: Isotonic saline intravenously Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Adult patients > 18 years undergoing an elective procedure involving intravascular administration of iodinated contrast media high risk for the development of Contrast Induced Nephropathy (as defined by guideline criteria Exclusion Criteria: Age < 18. Low risk for the development of CIN, therefore no need for hydration Emergency contrast procedure. Overt signs of overhydration; orthopnea or pulmonal rales at the time of the first consult. Double or triple diuretic use for pre-existing heart failure. Severe heart failure, in which case salt load is not safe (physician decision) Severe renal failure (CKD stage V eGFR < 15ml/min/1.73m2) Multiple Myeloma. Repeated contrast exposure < 2 weeks Unstable serum creatinine > 25% change < 6 weeks The inability to provide written informed consent. Participation in another intervention study Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Arm A: sodium chloride tablets<br>Arm A: sodium chloride 1g/10kg of body weight /day per os on day -2 and -1 before contrast exposure. With a maximum dose of 10 gram sodium chloride a day. | Drug: Sodium chloride tablets<br>* sodium chloride 1g/10kg of body weight /day per os on day -2 and -1 before contrast exposure. With a maximum dose of 10 gram sodium chloride a day.<br>| | Active Comparator: B: isotonic saline intravenously<br>Sodium chloride solution (isotonic saline (NaCl 0.9%) total 1000ml in 4 hrs or (in case of heart failure or severe renal failure) 12 hrs before and in 4 or in 12 hrs after contrast administration. | Drug: Isotonic saline intravenously<br>* isotonic saline (Nacl 0.9%) total 1000ml in 4 hrs or (in case of heart failure or severe renal failure) 12 hrs before and in 4 or in 12 hrs after contrast administration.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The primary endpoint will be change in the creatinine concentration between the 48-72 hours creatinine levels and the baseline levels, expressed as ratio. | | 48-72 hours after contrast administration | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | we will evaluate the incidence of contrast nephropathy in the groups defined as a rise in serum creatinine of ≥25% or ≥44umol/L 48-72 hours after contrast administration | | 48-72 hours after contrast administration | | patient satisfaction. | patient satisfacation will be evaluated using a questionnaire | up to 1 week after intervention | | the incidence of adverse events | | up to 1 week after intervention | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- contrast media, kidney injury, hydration

NCT00096681

Prevalence of HIV and Tuberculosis in Masiphumelele Township, Cape Town, South Africa

The purpose of this study is to estimate the amount of HIV and tuberculosis (TB) infection in individuals 15 years and older in the Masiphumelele township of Cape Town, South Africa. Data collected in this study will be used to predict the effect of introducing anti-HIV therapy in this community.

TB is the most common opportunistic infection among HIV infected people, and is the most common cause of death in HIV infected people in Africa. The Masiphumelele township of Cape Town, South Africa, with its high rates of TB and HIV, is representative of many poor communities of Africa. Via random sampling, this study will assess the prevalence of HIV and TB infections in the Masiphumelele township. Knowledge gained from this study will be used to predict if introducing antiretroviral therapy will reduce the prevalence of TB in this community.~Selection and enrollment of participants will last about 4 months. Potential participants will be visited in their homes by fieldworkers, who will explain the study. Participants will be invited to either go to the clinic on the day of the fieldworker's visit or to go on a different day. Participants who go to the clinic on the day of the visit will have two sputum samples collected with a nebulizer. Participants who do not go to the clinic on the visit day will be given a sputum sample bottle and will be asked to collect a sputum sample in the early morning the day before their clinic appointment. At the clinic appointment, another sputum sample will be collected from these participants. Direct smear acid-fast bacilli and Mycobacterium tuberculosis cultures will be done on both sputum samples. Participants who test positive for TB will be referred for TB treatment at the clinic. Participants will also be asked to complete a study questionnaire and will undergo an anonymous oral HIV test at the clinic visit.

Protocol for Cross-Sectional Survey of Acid-Fast Bacilli (AFB) Smear Positive and/or Culture Positive Tuberculosis in the Masiphumelele Township

HIV Infections, Tuberculosis

Inclusion Criteria:~Resident of the Masiphumelele township for at least 1 week prior to study entry~Willing to provide informed consent~Willing to comply with study requirements

15 Years

All

Accepts Healthy Volunteers

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants With Microbiologically Confirmed Pulmonary Tuberculosis | Confirmed Pulmonary Tuberculosis based on the sputum smear and culture results. The sputum sample was obtained at the once off study visit. | Pulmonary Tuberculosis diagnosed from sputum sample obtained at the study visit |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants With a Positive HIV Test | Prevalence of HIV in the community based on a positive oral mucosal transudate sample obtained at the once off study visit. | HIV status at the time of the study visit |

Tuberculosis, Infections, Mycobacterium Infections, Actinomycetales Infections, Gram-Positive Bacterial Infections, Bacterial Infections, Bacterial Infections and Mycoses

Prevalence of HIV and Tuberculosis in Masiphumelele Township, Cape Town, South Africa Study Overview ================= Brief Summary ----------------- The purpose of this study is to estimate the amount of HIV and tuberculosis (TB) infection in individuals 15 years and older in the Masiphumelele township of Cape Town, South Africa. Data collected in this study will be used to predict the effect of introducing anti-HIV therapy in this community. Detailed Description ----------------- TB is the most common opportunistic infection among HIV infected people, and is the most common cause of death in HIV infected people in Africa. The Masiphumelele township of Cape Town, South Africa, with its high rates of TB and HIV, is representative of many poor communities of Africa. Via random sampling, this study will assess the prevalence of HIV and TB infections in the Masiphumelele township. Knowledge gained from this study will be used to predict if introducing antiretroviral therapy will reduce the prevalence of TB in this community. Selection and enrollment of participants will last about 4 months. Potential participants will be visited in their homes by fieldworkers, who will explain the study. Participants will be invited to either go to the clinic on the day of the fieldworker's visit or to go on a different day. Participants who go to the clinic on the day of the visit will have two sputum samples collected with a nebulizer. Participants who do not go to the clinic on the visit day will be given a sputum sample bottle and will be asked to collect a sputum sample in the early morning the day before their clinic appointment. At the clinic appointment, another sputum sample will be collected from these participants. Direct smear acid-fast bacilli and Mycobacterium tuberculosis cultures will be done on both sputum samples. Participants who test positive for TB will be referred for TB treatment at the clinic. Participants will also be asked to complete a study questionnaire and will undergo an anonymous oral HIV test at the clinic visit. Official Title ----------------- Protocol for Cross-Sectional Survey of Acid-Fast Bacilli (AFB) Smear Positive and/or Culture Positive Tuberculosis in the Masiphumelele Township Conditions ----------------- HIV Infections, Tuberculosis Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Resident of the Masiphumelele township for at least 1 week prior to study entry Willing to provide informed consent Willing to comply with study requirements Ages Eligible for Study ----------------- Minimum Age: 15 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants With Microbiologically Confirmed Pulmonary Tuberculosis | Confirmed Pulmonary Tuberculosis based on the sputum smear and culture results. The sputum sample was obtained at the once off study visit. | Pulmonary Tuberculosis diagnosed from sputum sample obtained at the study visit | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants With a Positive HIV Test | Prevalence of HIV in the community based on a positive oral mucosal transudate sample obtained at the once off study visit. | HIV status at the time of the study visit |

NCT04295525

Carnosine Supplementation on Quantity/Quality of Oral Salivae.

The aim of this study is to elucidate the mutual relationship between salivae characteristics and oral microbiome and to compare them with common oral disease; furthermore, by using specific bioinformatic tools to analyse the data, the potentials of Carnosine in preventing/treating oral diseases and its mechanism of action will be addressed by using quantitative proteomics.

The pH of the oral cavity is a synthetic parameter that underlies a multifactorial process of continuous adjustment that includes the effect of salivae as a buffer and the contribution of the oral cavity microbiome. In some diseases of the oral cavity an alteration of these adjustment mechanisms is supposed to alter the normal flow of salivae and, consequently, the pH and the oral microbiome with the expansion of potentially pathogenic strains such as e.g. streptococcus viridans.~Carnosine (Car) is an endogenous dipeptide, composed of β-alanine and L-histidine, that was originally discovered in larger amounts in skeletal muscle of some vertebrates, including humans, showing a greater dependence on non-oxidative forms of energy metabolism. This peculiar association with muscular tissue and its pH-buffering properties has led to associate Car with the intracellular acid-base homeostasis of muscles. More recently, the physiological role of Car has been expanded beyond the intracellular buffering properties, supporting a role in sarcoplasmic Ca2+ regulation and neutralisation of reactive oxygen species (ROS). It is well known that ROS induce the formation of reactive electrophilic carbonyl species by reacting with lipids and sugars which, in turn, react with proteins forming irreversible adducts (AGEs, ALEs and EAGLEs) and cross-links that may affect the cardiovascular wall matrix that becomes less distensible, especially during the ageing process and/or diseases. Thus it is thought that Car and, indeed, other histidine-containing peptide (HCD), may prevent chronic diseases via their anti-inflammatory, anti-oxidative, anti-glycating, anti-ischaemic and chelating properties. Furthermore, the localisation of Car in other tissues such as brain, olfactory bulb, heart, stomach, pancreas, kidney has suggested further potential uses in preventing e.g. neurodegenerative disorder and cognitive function or the development of type II diabetes.~The oral microbiome (OM) is a relevant part of the whole human MO since it contains several different niches, with distinct microbial communities, colonising the oral cavity (OC), including not only bacteria but also fungi, viruses, archaea and protozoa. These communities form a complex ecological system that influences OC and systemic health. Indeed the prevalent oral diseases (OD), namely dental caries and periodontal diseases, are believed to be microbiota-related. Furthermore, several evidences support the theory that many systemic diseases are associated with an altered OM, among these the most frequently associated diseases are metabolic, such as diabetes, cardiovascular and oncological ones. For their prevalence worldwide, among OD, periodontal infection, including gingivitis and chronic periodontitis, is possibly the most prevalent human microbial diseases (HMD).~In order to protect the OC from HMD, in the present project Car has been chosen as a possible preventive and/or therapeutic principle for its aforementioned multiple biological effects. Thus the safety and efficacy of AqualiefTM (Metis Healthcare s.r.l., Milano, Italy) a 400 mg mucoadhesive oral tablet (13 x 4 mm), that recognise Car as main ingredient, will be tested on healthy volunteer and in subjects affected by common OD.~The main objectives of this protocol are to estimate the quantity/quality of oral salivae and OM in healthy volunteer and in patients affected by common OD, before and after 7 days of treatment with AqualiefTM, 1 tablet twice. The characteristics of oral salivae (Sal) that will be studied are:~a - unstimulated and stimulated (paraffin-activated) salivary flow rates, pH and buffering power; b - quantitative proteomics (QP), on selected targets, representing the main metabolites/components of OM.~By matching Sal characteristics with OM and comparing them with OD, it is expected to elucidate their mutual relationship; furthermore, by using specific bioinformatic tools to analyse the data, the potentials of Car in preventing/treating OD and its mechanism of action will be addressed by using QP.~The study will take place at the Odontoiatric University Clinic (OUC), Istituto Stomatologico Italiano (ISI) of Milan, Italy, in a prospective, randomised, double-blind, placebo-controlled fashion.

PHoral: Effects of Carnosine Supplementation on Quantity/Quality of Oral Salivae in Healthy Volunteer and in Subjects Affected by Common Oral Pathologies.

Oral Diseases

* Dietary Supplement: 400 mg mucoadhesive oral tablet * Dietary Supplement: placebo mucoadhesive oral tablet

Inclusion Criteria for Oral Diseased subjects:~dental erosions (De)~caries (Ca)~périodontopathies (Pe)~Exclusion Criteria for both:~allergies/intolerances to the consumption of Carnosine~taking other food supplements~any type of drug treatment (interview)~smoking~pregnancy/lactation~any systemic diseases such as cardiovascular and respiratory, diabetes mellitus, HIV infection, or inflammatory conditions causing non-plaque dependent OD.

18 Years

40 Years

All

Accepts Healthy Volunteers

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Effects on oral pH. | Any change of oral pH from basal. | 7 days | | Saliva Production unstimulated. | Change of oral saliva production, unstimulated. | 7 days | | Saliva Production stimulated. | Change of oral saliva production, stimulated. | 7 days |

dental erosions, caries, périodontopathies

Mouth Diseases, Stomatognathic Diseases

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: Controls subjects placebo<br>Placebo mucoadhesive oral tablet | Dietary Supplement: placebo mucoadhesive oral tablet<br>* placebo<br>| | Experimental: Controls subjects active Treatment<br>AqualiefTM 400 mg mucoadhesive oral tablet | Dietary Supplement: 400 mg mucoadhesive oral tablet<br>* AqualiefTM (Metis Healthcare s.r.l., Milano, Italy)<br>| | Placebo Comparator: Diseased subjects placebo<br>Placebo mucoadhesive oral tablet | Dietary Supplement: placebo mucoadhesive oral tablet<br>* placebo<br>| | Experimental: Diseased subjects active Treatment<br>AqualiefTM 400 mg mucoadhesive oral tablet | Dietary Supplement: 400 mg mucoadhesive oral tablet<br>* AqualiefTM (Metis Healthcare s.r.l., Milano, Italy)<br>|

Carnosine Supplementation on Quantity/Quality of Oral Salivae. Study Overview ================= Brief Summary ----------------- The aim of this study is to elucidate the mutual relationship between salivae characteristics and oral microbiome and to compare them with common oral disease; furthermore, by using specific bioinformatic tools to analyse the data, the potentials of Carnosine in preventing/treating oral diseases and its mechanism of action will be addressed by using quantitative proteomics. Detailed Description ----------------- The pH of the oral cavity is a synthetic parameter that underlies a multifactorial process of continuous adjustment that includes the effect of salivae as a buffer and the contribution of the oral cavity microbiome. In some diseases of the oral cavity an alteration of these adjustment mechanisms is supposed to alter the normal flow of salivae and, consequently, the pH and the oral microbiome with the expansion of potentially pathogenic strains such as e.g. streptococcus viridans. Carnosine (Car) is an endogenous dipeptide, composed of β-alanine and L-histidine, that was originally discovered in larger amounts in skeletal muscle of some vertebrates, including humans, showing a greater dependence on non-oxidative forms of energy metabolism. This peculiar association with muscular tissue and its pH-buffering properties has led to associate Car with the intracellular acid-base homeostasis of muscles. More recently, the physiological role of Car has been expanded beyond the intracellular buffering properties, supporting a role in sarcoplasmic Ca2+ regulation and neutralisation of reactive oxygen species (ROS). It is well known that ROS induce the formation of reactive electrophilic carbonyl species by reacting with lipids and sugars which, in turn, react with proteins forming irreversible adducts (AGEs, ALEs and EAGLEs) and cross-links that may affect the cardiovascular wall matrix that becomes less distensible, especially during the ageing process and/or diseases. Thus it is thought that Car and, indeed, other histidine-containing peptide (HCD), may prevent chronic diseases via their anti-inflammatory, anti-oxidative, anti-glycating, anti-ischaemic and chelating properties. Furthermore, the localisation of Car in other tissues such as brain, olfactory bulb, heart, stomach, pancreas, kidney has suggested further potential uses in preventing e.g. neurodegenerative disorder and cognitive function or the development of type II diabetes. The oral microbiome (OM) is a relevant part of the whole human MO since it contains several different niches, with distinct microbial communities, colonising the oral cavity (OC), including not only bacteria but also fungi, viruses, archaea and protozoa. These communities form a complex ecological system that influences OC and systemic health. Indeed the prevalent oral diseases (OD), namely dental caries and periodontal diseases, are believed to be microbiota-related. Furthermore, several evidences support the theory that many systemic diseases are associated with an altered OM, among these the most frequently associated diseases are metabolic, such as diabetes, cardiovascular and oncological ones. For their prevalence worldwide, among OD, periodontal infection, including gingivitis and chronic periodontitis, is possibly the most prevalent human microbial diseases (HMD). In order to protect the OC from HMD, in the present project Car has been chosen as a possible preventive and/or therapeutic principle for its aforementioned multiple biological effects. Thus the safety and efficacy of AqualiefTM (Metis Healthcare s.r.l., Milano, Italy) a 400 mg mucoadhesive oral tablet (13 x 4 mm), that recognise Car as main ingredient, will be tested on healthy volunteer and in subjects affected by common OD. The main objectives of this protocol are to estimate the quantity/quality of oral salivae and OM in healthy volunteer and in patients affected by common OD, before and after 7 days of treatment with AqualiefTM, 1 tablet twice. The characteristics of oral salivae (Sal) that will be studied are: a - unstimulated and stimulated (paraffin-activated) salivary flow rates, pH and buffering power; b - quantitative proteomics (QP), on selected targets, representing the main metabolites/components of OM. By matching Sal characteristics with OM and comparing them with OD, it is expected to elucidate their mutual relationship; furthermore, by using specific bioinformatic tools to analyse the data, the potentials of Car in preventing/treating OD and its mechanism of action will be addressed by using QP. The study will take place at the Odontoiatric University Clinic (OUC), Istituto Stomatologico Italiano (ISI) of Milan, Italy, in a prospective, randomised, double-blind, placebo-controlled fashion. Official Title ----------------- PHoral: Effects of Carnosine Supplementation on Quantity/Quality of Oral Salivae in Healthy Volunteer and in Subjects Affected by Common Oral Pathologies. Conditions ----------------- Oral Diseases Intervention / Treatment ----------------- * Dietary Supplement: 400 mg mucoadhesive oral tablet * Dietary Supplement: placebo mucoadhesive oral tablet Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria for Oral Diseased subjects: dental erosions (De) caries (Ca) périodontopathies (Pe) Exclusion Criteria for both: allergies/intolerances to the consumption of Carnosine taking other food supplements any type of drug treatment (interview) smoking pregnancy/lactation any systemic diseases such as cardiovascular and respiratory, diabetes mellitus, HIV infection, or inflammatory conditions causing non-plaque dependent OD. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 40 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: Controls subjects placebo<br>Placebo mucoadhesive oral tablet | Dietary Supplement: placebo mucoadhesive oral tablet<br>* placebo<br>| | Experimental: Controls subjects active Treatment<br>AqualiefTM 400 mg mucoadhesive oral tablet | Dietary Supplement: 400 mg mucoadhesive oral tablet<br>* AqualiefTM (Metis Healthcare s.r.l., Milano, Italy)<br>| | Placebo Comparator: Diseased subjects placebo<br>Placebo mucoadhesive oral tablet | Dietary Supplement: placebo mucoadhesive oral tablet<br>* placebo<br>| | Experimental: Diseased subjects active Treatment<br>AqualiefTM 400 mg mucoadhesive oral tablet | Dietary Supplement: 400 mg mucoadhesive oral tablet<br>* AqualiefTM (Metis Healthcare s.r.l., Milano, Italy)<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Effects on oral pH. | Any change of oral pH from basal. | 7 days | | Saliva Production unstimulated. | Change of oral saliva production, unstimulated. | 7 days | | Saliva Production stimulated. | Change of oral saliva production, stimulated. | 7 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- dental erosions, caries, périodontopathies

NCT05304065

Youth Partners in Care for Suicide Prevention

This randomized comparative effectiveness trial will compare two evidence-based approaches to emergency care for youth ages 15-24 who present to the Emergency Department (ED) with suicidal ideation or behavior. OUtcomes will be monitored at baseline and at 3, 6 & 12 month follow-up assessments.

Rationale and Importance of Study:~Suicide is currently the second leading cause of death for U.S. youth ages 15-24, responsible for more deaths than any major illness. Youth with serious suicidal behavior or thoughts often present to the nation's Emergency Departments (EDs), particularly youth who make potentially deadly suicide attempts. Evidence is limited regarding optimal interventions for reducing the risk of fatal and nonfatal suicide attempts in these youth, and tested interventions include multiple components. One dimension along which these interventions vary is timing. Some interventions are delivered in the ED, others focus on aftercare, and others combine ED and aftercare interventions. Current evidence supports effectiveness of some interventions for reducing later suicide attempts and improving the likelihood that youth will receive mental health treatment after leaving the ED. However, evidence gaps exist regarding: 1) whether it is sufficient to focus on providing an evidence-based intervention in the ED, or whether a post-ED aftercare intervention is needed to improve youth outcomes; and 2) for which patient subgroups a combined ED and aftercare treatment may be indicated. Answering these questions is vital for guiding resource allocation, as ED care emphasizes care in the ED with limited resources for aftercare.~Study Aims:~The study addresses this evidence gap by comparing two evidence-based interventions for reducing suicide attempts and improving outcomes for youth presenting to EDs with suicidal episodes: 1) Safety-Acute(A) integrated within ED care, a crisis therapy/safety planning intervention in the ED focused on enhancing safety (previously called Family Intervention for Suicide Prevention, FISP); and 2) SAFETY-A/ED care plus the Coping Long-term with Active Suicide Program (CLASP), comprised of brief therapeutic follow-up contacts after discharge from the ED/hospital. Evidence supports benefits of both interventions individually. SAFETY-A/FISP is listed in the National Register of Evidence-Based Practices, and CLASP is being implemented in some Veterans Administration Hospitals. The first aim is to evaluate whether SAFETY-A/ED Care combined with CLASP aftercare is superior to SAFETY- A/ED Care alone for reducing the risk of suicide attempts and increasing initiation of follow-up mental health treatment. Second, the investigators examine heterogeneity of treatment effects among subgroups, hypothesizing that in this large diverse sample the strongest benefits of the combined SAFETY-A/ED Care plus CLASP intervention will be seen in youth who are from ethnic or racial minority groups, socioeconomically disadvantaged, and from rural communities. Third, the investigators aim to increase the value and relevance of the study by engaging patients, parents, family members, providers, and health and mental healthcare system stakeholders in project leadership and activities throughout the study and implement a partnered dissemination plan to enhance the potential for study findings to inform clinical practice and health care delivery.~Study Description:~The patient population includes 1,516 youth ages 15-24 presenting to EDs with suicidal ideation or behavior in 4 communities across the country selected to include a diverse population (racial, ethnic, rural vs urban, public vs private insurance): California/Los Angeles; North Carolina; Rhode Island; Utah. Youth are randomly assigned to: 1) SAFETY-A/ED Care; or 2) SAFETY-A/ED Care plus CLASP. Assessments are conducted at the start of the study and at 3, 6, and 12-month follow-ups. Primary outcomes are suicide attempts and mental health treatment initiation. Secondary outcomes are overall self-harm (including suicide attempts and non-suicidal self-harm) and treatment engagement/dose. Exploratory outcomes are: severity of youth suicidality; youth functioning and quality of life; and improvement on three problems prioritized by the youth and parent or significant other as top problems. The investigators also examine change in identified protective and risk factors (e.g. connectedness, hopelessness, and perceived barriers to treatment). The investigators partner with diverse stakeholders, develop a Stakeholder Council, and include stakeholder partners in project leadership and activities with the goals of promoting 2-way knowledge exchange and enhancing the value of the study for improving patient care and outcomes.~Significance:~Study results will clarify whether the additional resources needed to provide brief therapeutic follow-up calls after an ED intervention leads to improved outcomes, and which patient subgroups are most likely to benefit from a treatment approach that provides therapeutic contact both during the ED visit and after discharge from the ED. This information can guide decision makers regarding how to best develop services and service systems to improve patient outcomes and achieve national suicide prevention goals, including for diverse groups to improve equity.

Youth Partners in Care for Suicide Prevention

Suicide and Self-harm

* Behavioral: SAFETY-A within usual ED Care * Behavioral: Combined SAFETY-A within usual ED Care + CLASP Therapeutic Follow-Up Contacts

Inclusion Criteria:~age 15-24;~past-week suicidal behavior or ideation with plan or intent~Exclusion Criteria:~symptoms or illness that precludes informed consent or engagement in study procedures (e.g., active psychosis; drug dependence, no locator information);~youth not fluent in English~parent not fluent in English or Spanish.

15 Years

24 Years

All

No

Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Suicide Attempts: Primary Clinical Outcome | suicide attempts fatal, nonfatal, and interrupted | Through 12 months of follow-up | | Mental Health Treatment Initiation: Primary Service Use Outcome | initiation of mental health treatment after discharge from ED/hospital | Through 12 months of follow-up |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Self-Harm: Secondary Clinical Outcome | Any self-harm including suicidal, nonsuicidal, and ambiguous self-harm | Through 12 months of follow-up | | Treatment engagement: Secondary Service Use Outcome | Treatment dose received | Through 12 months of follow-up |

Suicide, Suicide Prevention, Self-Injurious Behavior, Behavioral Symptoms

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: SAFETY-Acute within Usual ED Care<br>The SAFETY-Acute (A) approach to safety planning and stabilization will be integrated within usual ED Care. SAFETY-A was formerly called the Family Intervention for Suicide Prevention, FISP. | Behavioral: SAFETY-A within usual ED Care<br>* SAFETY-A is a single session collaborative, strengths-based, developmentally nuanced, cognitive-behavioral intervention (CBT) to increase safety and mental health treatment initiation. The therapist works with the youth and family (or significant other, SO) separately and together to build hope and reasons for living, develop a personal safety plan, increase protective supports; and increase motivation for and linkage to treatment.<br>* Other names: Family Intervention for Suicide Prevention (FISP);| | Active Comparator: Combined<br>The combined treatment arm includes both 1) SAFETY-A integrated within usual ED Care, and 2) therapeutic follow-up contacts using the Coping Long Term with Active Suicidality Program (CLASP) model. | Behavioral: Combined SAFETY-A within usual ED Care + CLASP Therapeutic Follow-Up Contacts<br>* COMB, includes SAFETY-A within usual ED care plus CLASP therapeutic and caring follow-up contacts designed to strengthen safety and treatment initiation and engagement. Core functions of CLASP include: building hope/reducing hopelessness; enhancing social/family support; strengthening problem-solving; and increasing treatment initiation and engagement.<br>|

Youth Partners in Care for Suicide Prevention Study Overview ================= Brief Summary ----------------- This randomized comparative effectiveness trial will compare two evidence-based approaches to emergency care for youth ages 15-24 who present to the Emergency Department (ED) with suicidal ideation or behavior. OUtcomes will be monitored at baseline and at 3, 6 & 12 month follow-up assessments. Detailed Description ----------------- Rationale and Importance of Study: Suicide is currently the second leading cause of death for U.S. youth ages 15-24, responsible for more deaths than any major illness. Youth with serious suicidal behavior or thoughts often present to the nation's Emergency Departments (EDs), particularly youth who make potentially deadly suicide attempts. Evidence is limited regarding optimal interventions for reducing the risk of fatal and nonfatal suicide attempts in these youth, and tested interventions include multiple components. One dimension along which these interventions vary is timing. Some interventions are delivered in the ED, others focus on aftercare, and others combine ED and aftercare interventions. Current evidence supports effectiveness of some interventions for reducing later suicide attempts and improving the likelihood that youth will receive mental health treatment after leaving the ED. However, evidence gaps exist regarding: 1) whether it is sufficient to focus on providing an evidence-based intervention in the ED, or whether a post-ED aftercare intervention is needed to improve youth outcomes; and 2) for which patient subgroups a combined ED and aftercare treatment may be indicated. Answering these questions is vital for guiding resource allocation, as ED care emphasizes care in the ED with limited resources for aftercare. Study Aims: The study addresses this evidence gap by comparing two evidence-based interventions for reducing suicide attempts and improving outcomes for youth presenting to EDs with suicidal episodes: 1) Safety-Acute(A) integrated within ED care, a crisis therapy/safety planning intervention in the ED focused on enhancing safety (previously called Family Intervention for Suicide Prevention, FISP); and 2) SAFETY-A/ED care plus the Coping Long-term with Active Suicide Program (CLASP), comprised of brief therapeutic follow-up contacts after discharge from the ED/hospital. Evidence supports benefits of both interventions individually. SAFETY-A/FISP is listed in the National Register of Evidence-Based Practices, and CLASP is being implemented in some Veterans Administration Hospitals. The first aim is to evaluate whether SAFETY-A/ED Care combined with CLASP aftercare is superior to SAFETY- A/ED Care alone for reducing the risk of suicide attempts and increasing initiation of follow-up mental health treatment. Second, the investigators examine heterogeneity of treatment effects among subgroups, hypothesizing that in this large diverse sample the strongest benefits of the combined SAFETY-A/ED Care plus CLASP intervention will be seen in youth who are from ethnic or racial minority groups, socioeconomically disadvantaged, and from rural communities. Third, the investigators aim to increase the value and relevance of the study by engaging patients, parents, family members, providers, and health and mental healthcare system stakeholders in project leadership and activities throughout the study and implement a partnered dissemination plan to enhance the potential for study findings to inform clinical practice and health care delivery. Study Description: The patient population includes 1,516 youth ages 15-24 presenting to EDs with suicidal ideation or behavior in 4 communities across the country selected to include a diverse population (racial, ethnic, rural vs urban, public vs private insurance): California/Los Angeles; North Carolina; Rhode Island; Utah. Youth are randomly assigned to: 1) SAFETY-A/ED Care; or 2) SAFETY-A/ED Care plus CLASP. Assessments are conducted at the start of the study and at 3, 6, and 12-month follow-ups. Primary outcomes are suicide attempts and mental health treatment initiation. Secondary outcomes are overall self-harm (including suicide attempts and non-suicidal self-harm) and treatment engagement/dose. Exploratory outcomes are: severity of youth suicidality; youth functioning and quality of life; and improvement on three problems prioritized by the youth and parent or significant other as top problems. The investigators also examine change in identified protective and risk factors (e.g. connectedness, hopelessness, and perceived barriers to treatment). The investigators partner with diverse stakeholders, develop a Stakeholder Council, and include stakeholder partners in project leadership and activities with the goals of promoting 2-way knowledge exchange and enhancing the value of the study for improving patient care and outcomes. Significance: Study results will clarify whether the additional resources needed to provide brief therapeutic follow-up calls after an ED intervention leads to improved outcomes, and which patient subgroups are most likely to benefit from a treatment approach that provides therapeutic contact both during the ED visit and after discharge from the ED. This information can guide decision makers regarding how to best develop services and service systems to improve patient outcomes and achieve national suicide prevention goals, including for diverse groups to improve equity. Official Title ----------------- Youth Partners in Care for Suicide Prevention Conditions ----------------- Suicide and Self-harm Intervention / Treatment ----------------- * Behavioral: SAFETY-A within usual ED Care * Behavioral: Combined SAFETY-A within usual ED Care + CLASP Therapeutic Follow-Up Contacts Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: age 15-24; past-week suicidal behavior or ideation with plan or intent Exclusion Criteria: symptoms or illness that precludes informed consent or engagement in study procedures (e.g., active psychosis; drug dependence, no locator information); youth not fluent in English parent not fluent in English or Spanish. Ages Eligible for Study ----------------- Minimum Age: 15 Years Maximum Age: 24 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: SAFETY-Acute within Usual ED Care<br>The SAFETY-Acute (A) approach to safety planning and stabilization will be integrated within usual ED Care. SAFETY-A was formerly called the Family Intervention for Suicide Prevention, FISP. | Behavioral: SAFETY-A within usual ED Care<br>* SAFETY-A is a single session collaborative, strengths-based, developmentally nuanced, cognitive-behavioral intervention (CBT) to increase safety and mental health treatment initiation. The therapist works with the youth and family (or significant other, SO) separately and together to build hope and reasons for living, develop a personal safety plan, increase protective supports; and increase motivation for and linkage to treatment.<br>* Other names: Family Intervention for Suicide Prevention (FISP);| | Active Comparator: Combined<br>The combined treatment arm includes both 1) SAFETY-A integrated within usual ED Care, and 2) therapeutic follow-up contacts using the Coping Long Term with Active Suicidality Program (CLASP) model. | Behavioral: Combined SAFETY-A within usual ED Care + CLASP Therapeutic Follow-Up Contacts<br>* COMB, includes SAFETY-A within usual ED care plus CLASP therapeutic and caring follow-up contacts designed to strengthen safety and treatment initiation and engagement. Core functions of CLASP include: building hope/reducing hopelessness; enhancing social/family support; strengthening problem-solving; and increasing treatment initiation and engagement.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Suicide Attempts: Primary Clinical Outcome | suicide attempts fatal, nonfatal, and interrupted | Through 12 months of follow-up | | Mental Health Treatment Initiation: Primary Service Use Outcome | initiation of mental health treatment after discharge from ED/hospital | Through 12 months of follow-up | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Self-Harm: Secondary Clinical Outcome | Any self-harm including suicidal, nonsuicidal, and ambiguous self-harm | Through 12 months of follow-up | | Treatment engagement: Secondary Service Use Outcome | Treatment dose received | Through 12 months of follow-up |

NCT01582919

Neuroimaging Markers of Alzheimer Disease: a Longitudinal Population Study

It is now acknowledged that Alzheimer's disease is characterized by a long period of pathophysiological change. Developing new strategies to achieve diagnoses as early as possible has become a major goal for therapies aimed at slowing the progression of this disease. While diagnoses currently rely principally on clinical neuropsychology, the typical diagnostic criteria of NINCDS-ADRDA are inapplicable in the early stage of the disease. The goal of our project is to identify very early imaging markers for Alzheimer's disease among patients with no report of cognitive difficulties. In order to achieve this goal, we propose a longitudinal study in an elderly population cohort.

The AMImage2 project that follows AMImage1 and MRI-3C consists of an imaging study in association with longitudinal epidemiologic cohorts (AMI and 3C). The first objective is to investigate the association between the evolution of imaging markers and the evolution of cognitive performance in normal and pathological aging. This objective will be conducted among subjects having already participated in AMImage1, thereby permitting the longitudinal study of MRI data. An MRI exam will also be proposed to 100 subjects (members of the AMI and 3C cohorts) in order to provide a third wave of MRI (for a longer-term MRI follow-up) or a second one for the participants who only had one MRI exam in the AMImage project. Our second objective is cross-sectional and will study the imaging parameters of subjects presenting signs of cognitive decline over the previous 4 years (through the follow-up conducted in the AMI cohort). Finally, an additional objective will consist in a comparison between two populations very contrasted in terms of cognitive reserve: AMI (very low education level in rural area) and 3C (higher level of education in urban area).

STUDY OF IMAGING MARKERS IN THE VERY EARLY STAGES OF DEMENTIA AMONG RETIRED RURAL FARM IN THE GIRONDE AND PARTICIPATING IN THE AMI COHORT EPIDEMIOLOGY: A LONGITUDINAL STUDY.

Dementia, Alzheimer Disease

* Other: Neuroimaging

Inclusion Criteria:~At least 65 years old~Be retired from agricultural profession~live in rural area in Gironde (France)~Exclusion Criteria:~Lefthanded~having a dementia (MMSE < 13)~Having a vascular cerebral accident~Parkinson disease~RMI exclusion criteria~[18F]-FDG PET SCAN exclusion criteria~Poor health condition does not allowing transport to neuroimaging service

65 Years

All

No

Primary Purpose: Diagnostic Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Measures of volume and diffusion parameters in the gray matter (hippocampus and cingular posterior cortex) | | Inclusion (Day 0) |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Performance on neuropsychological and daily life cognitive tests | | Everyday up to Day 7 after inclusion |

dementia, Alzheimer's Disease, diagnostic, biomarkers, neuroimaging, PET, MRI, mild cognitive impairment

Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Participant from AMI cohort<br> | Other: Neuroimaging<br> <br> | | Active Comparator: Participant from 3Ccohort<br> | Other: Neuroimaging<br> <br> |

Neuroimaging Markers of Alzheimer Disease: a Longitudinal Population Study Study Overview ================= Brief Summary ----------------- It is now acknowledged that Alzheimer's disease is characterized by a long period of pathophysiological change. Developing new strategies to achieve diagnoses as early as possible has become a major goal for therapies aimed at slowing the progression of this disease. While diagnoses currently rely principally on clinical neuropsychology, the typical diagnostic criteria of NINCDS-ADRDA are inapplicable in the early stage of the disease. The goal of our project is to identify very early imaging markers for Alzheimer's disease among patients with no report of cognitive difficulties. In order to achieve this goal, we propose a longitudinal study in an elderly population cohort. Detailed Description ----------------- The AMImage2 project that follows AMImage1 and MRI-3C consists of an imaging study in association with longitudinal epidemiologic cohorts (AMI and 3C). The first objective is to investigate the association between the evolution of imaging markers and the evolution of cognitive performance in normal and pathological aging. This objective will be conducted among subjects having already participated in AMImage1, thereby permitting the longitudinal study of MRI data. An MRI exam will also be proposed to 100 subjects (members of the AMI and 3C cohorts) in order to provide a third wave of MRI (for a longer-term MRI follow-up) or a second one for the participants who only had one MRI exam in the AMImage project. Our second objective is cross-sectional and will study the imaging parameters of subjects presenting signs of cognitive decline over the previous 4 years (through the follow-up conducted in the AMI cohort). Finally, an additional objective will consist in a comparison between two populations very contrasted in terms of cognitive reserve: AMI (very low education level in rural area) and 3C (higher level of education in urban area). Official Title ----------------- STUDY OF IMAGING MARKERS IN THE VERY EARLY STAGES OF DEMENTIA AMONG RETIRED RURAL FARM IN THE GIRONDE AND PARTICIPATING IN THE AMI COHORT EPIDEMIOLOGY: A LONGITUDINAL STUDY. Conditions ----------------- Dementia, Alzheimer Disease Intervention / Treatment ----------------- * Other: Neuroimaging Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: At least 65 years old Be retired from agricultural profession live in rural area in Gironde (France) Exclusion Criteria: Lefthanded having a dementia (MMSE < 13) Having a vascular cerebral accident Parkinson disease RMI exclusion criteria [18F]-FDG PET SCAN exclusion criteria Poor health condition does not allowing transport to neuroimaging service Ages Eligible for Study ----------------- Minimum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Diagnostic Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Participant from AMI cohort<br> | Other: Neuroimaging<br> <br> | | Active Comparator: Participant from 3Ccohort<br> | Other: Neuroimaging<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Measures of volume and diffusion parameters in the gray matter (hippocampus and cingular posterior cortex) | | Inclusion (Day 0) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Performance on neuropsychological and daily life cognitive tests | | Everyday up to Day 7 after inclusion | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- dementia, Alzheimer's Disease, diagnostic, biomarkers, neuroimaging, PET, MRI, mild cognitive impairment

NCT04378335

Assessment of Orality Disorders in Children With Food Allergies

Orality disorders are frequent in child. There are complications like growth and psychomotor development disorders.~The aim is to estimate the prevalence of orality disorder for child with one or several food allergy.

Assessment of Orality Disorders in Children With Food Allergies

Food Allergy in Children, 6 Years Old Maximum

* Other: completion of questionnaire

Inclusion Criteria:~Every child aged between 6 month and 6 years, with one or several food allergy and under the care of allergy unity of University Hospital of Angers~obtention of informed consent~Exclusion Criteria:~Child with allergy other than food~poor understanding of french

6 Months

6 Years

All

No

Primary Purpose: Supportive Care Intervention Model: Single Group Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Prevalence of orality disorder in children with food allergy | | Enrollment |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Link between orality disorder and number of excluded food, time from excluded regimen, age of the beginning of diet diversification, breastfeeding and duration,status of the child in the family and demographic data. | All data will be collected by a questionnaire established by Angers Hospital | Enrollment | | Link between food allergies and orality disorder | data will be collected by a questionnaire | Enrollment | | Prevalence of dysphagia criteria | | Enrollment |

Hypersensitivity, Food Hypersensitivity, Immune System Diseases, Hypersensitivity, Immediate

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: one arm<br>oral disorder | Other: completion of questionnaire<br>* parents have to complete 2 questionnaires: demographic questionnaire and Montréal questionnaire when they come on allergy consultation.<br>|

Assessment of Orality Disorders in Children With Food Allergies Study Overview ================= Brief Summary ----------------- Orality disorders are frequent in child. There are complications like growth and psychomotor development disorders. The aim is to estimate the prevalence of orality disorder for child with one or several food allergy. Official Title ----------------- Assessment of Orality Disorders in Children With Food Allergies Conditions ----------------- Food Allergy in Children, 6 Years Old Maximum Intervention / Treatment ----------------- * Other: completion of questionnaire Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Every child aged between 6 month and 6 years, with one or several food allergy and under the care of allergy unity of University Hospital of Angers obtention of informed consent Exclusion Criteria: Child with allergy other than food poor understanding of french Ages Eligible for Study ----------------- Minimum Age: 6 Months Maximum Age: 6 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: one arm<br>oral disorder | Other: completion of questionnaire<br>* parents have to complete 2 questionnaires: demographic questionnaire and Montréal questionnaire when they come on allergy consultation.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Prevalence of orality disorder in children with food allergy | | Enrollment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Link between orality disorder and number of excluded food, time from excluded regimen, age of the beginning of diet diversification, breastfeeding and duration,status of the child in the family and demographic data. | All data will be collected by a questionnaire established by Angers Hospital | Enrollment | | Link between food allergies and orality disorder | data will be collected by a questionnaire | Enrollment | | Prevalence of dysphagia criteria | | Enrollment |

NCT03923231

Pharmacokinetics of Atazanavir in Special Populations

The lack of data relating to the DDI between ATV and RIF is a major limitation to the use of ATV in patients who require treatment for TB. The VirTUAL Workpackage 2 will explore the necessary dose escalation required to overcome this interaction in non-pregnant HIV-infected adults who are virologically suppressed on bPI-based ART, and who are administered RIF as a study drug, not as part of a full TB treatment regimen. As the specific objective of WP2 is to define the dose of ATV, participants taking an alternative bPI will be transitioned to ATV for the duration of that study. However, to extrapolate the results of this study to special populations such as pregnant and postpartum women, children and adolescents and those with other 'special' characteristics such as obesity (BMI >30 Kg/m2) or malnutrition (BMI <18.5 Kg/m2) we propose to undertake sparse sampling for pharmacokinetic analysis from individuals who require ATV-based ART for their clinical care.~Sparse PK data will be obtained opportunistically from participants in the 'special populations' defined above who are receiving ATV as part of their routine clinical care. Subjects will be identified from clinics including the Joint Clinical Research Center (JCRC) and Infectious Diseases Institute (IDI), Kampala, and from sites including Groote Schuur Hospital and Gugulethu Community Health Centre, Cape Town. The ATV/r data from special populations will enable validation and refinement of both the PBPK model (WP1) and the pop-PK models (WP4) of the VirTUAL consortium.

Overview of VirTUAL Consortium Through the VirTUAL Consortium, the investigators aim to define the optimal use of second-line ART regimens in vulnerable populations with TB co-infection. The primary objective is to 'to determine the optimal dose of boosted atazanavir (ATV/r) when used in combination with RIF-based TB treatment in children, adolescents and pregnant or breastfeeding women.'~The results from this protocol (VirTUAL WP5) will be considered in the context of the full research programme. This can be summarised as follows:~Physiologically-based pharmacokinetic (PBPK) modelling will be developed to understand bPI and RIF Drug-Drug Interactions (DDIs), identifying potential dosing strategies to overcome these in adults and special populations (WP1). This data will inform clinical pharmacokinetic studies exploring the necessary dose escalation of ATV/r, including in the context of high-dose RIF, performed in Kampala (WP2). Intracellular pharmacokinetics will further characterise the DDI (WP3). PBPK and population pharmacokinetics (pop-PK) modelling will be integrated enabling extrapolation to special populations (WP4), and sparse data collection from such populations receiving different combinations of second-line ART and/or TB treatment in Kampala and Cape Town will validate and refine these models (WP5). Capacity building focussing on equipping African scientists with the tools to efficiently define drug dosing in complex populations (WP6), communication and stakeholder engagement (WP7) will increase the application of this methodology to other priority research into pharmacokinetics in special populations.~This protocol describes the sparse pharmacokinetic sampling component which forms Workpackage 5 (WP5) of this research programme. The dose-escalation study (WP2) is an interventional trial which will be conducted in 28 healthy, virologically suppressed volunteers who are on ATV-based second-line ART, are aged over 18, have a normal BMI and are not pregnant or breastfeeding, and which will take place at JCRC, Kampala, Uganda. This study is anticipated to commence in mid-2019, and will explore in detail the changes in pharmacokinetics of ATV/r in both plasma and within cells which take place when rifampicin is co-administered, and will evaluate the necessary dose adjustment which is required to concurrently administer ATV/r with rifampicin-based TB treatment. WP2 will generate intensive data on these 28 well characterized individuals who do not have 'special' characteristics. However, there is a paucity of data on ATV/r disposition in patients who are typically excluded from clinical trials, and therefore the observational data from WP5 will be collected from individuals who fall into the listed categories of special populations and who are being treated with ATV/r for their own health. Data from either WP2 or WP5 alone will be amenable to pharmacometric analysis and bring value, but the combined modelling approach using both sets of data in a combined model will allow the most comprehensive evaluation of ATV/r disposition in the wider population, and will enable projections of dosing recommendations for the special populations who require concurrent treatment for TB whilst receiving ATV/r-based ART.~Individuals will be identified at routine clinic appointments. They (or their guardians) will be asked to keep a detailed record of dosing times for three to five days prior to their study appointment at which sampling will be performed. If they take their medication in the morning, they will be asked to bring the medication to clinic for observation of dosing.~Repeat sampling at subsequent appointments will enable assessment of both between and within-individual variability, for example during periods of rapid childhood growth or during pregnancy and transition back to non-pregnant physiological state.~It is aimed to obtain 20 sparse PK profiles in each of the following groups (pregnant, child <5, child 6-11, adolescent 12-18, obese (BMI >30 Kg/m2), malnourished (BMI <18.5 Kg/m2)), with each individual contributing 4 samples per PK visit, and possibly followed up longitudinally during the study (each individual may attend for a maximum of three study visits). Therefore there will be between 7 (6 participants being sampled on 3 occasions and a final participant sampled on 2 occasions) and 20 (if each participant was only sampled on a single occasion) individual participants per group to generate the 20 sampling 'occasions', with a total number of participants across the six groups included in the study of between 42 and 120.~This will provide an essential clinical dataset to inform the pop-PK modelling approach and validate the PBPK simulations, describing exposure and pharmacokinetic variability in the populations of interest. The data from this work package will be pooled with the data from the study in volunteers and jointly analysed using PK modelling. Differences in the PK parameters for each of the groups will be investigated.~There exist no peer-reviewed published data regarding the transfer of ATV/r into breast milk. Therefore, among women who are enrolled during pregnancy and followed into the postpartum phase, paired breast milk samples will be obtained at the same time as plasma samples.

Investigation of the Pharmacokinetics of Atazanavir in Pregnant Women, Individuals at Extremes of BMI, Children, and Adolescents: An Observational Study Nested Within the VirTUAL Consortium

HIV/AIDS, Tuberculosis

* Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily * Drug: Atazanavir 250 mg / ritonavir 80 mg

Inclusion Criteria:~Evidence of a personally signed and dated informed consent document indicating that the participant (or a legal representative) has been informed of all pertinent aspects of the study.~In a child aged ≥7 years (South Africa) or aged ≥8 years (Uganda), evidence of assent to participate~Participants who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures.~HIV-infected, receiving ATV-based ART treatment OR HIV-infected receiving second-line ART with concurrent rifamycin-based TB treatment~Participant is within one of the target populations:~Pregnant (>20 weeks)~Body mass index >30 or <18.5 Kg/m2~Child or adolescent aged <18 years~Exclusion Criteria:~Medical, psychiatric or obstetric condition that might affect participation in the stuy based on investigator judgement~Dissent from a minor~For pregnant women in Uganda, where the husband is reasonably involved, paternal objection

All

No

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Atazanavir Cmax | To describe the maximum concentration of atazanavir reached after dosing in the different groups | 3 years | | Atazanavir AUC0-24 | To describe the area under the concentration-time curve from 0 to 24 hours after dosing in the different groups | 3 years | | Atazanavir Ctau | To describe the trough concentration of atazanavir after dosing in the different study groups | 3 years |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Comparison of geometric mean of atazanavir Cmax with healthy adult population | To compare atazanavir Cmax with typical healthy individuals treated with atazanavir who enter a dose escalation study of ATV/r + RIF as WP2 of the VirTUAL programme | 3 years | | Comparison of geometric mean of atazanavir AUC0-24 with healthy adult population | To compare atazanavir AUC0-24 with that of typical healthy adults treated with atazanavir-based ART who enter a dose escalation study of ATV/r + RIF as WP2 of the VirTUAL programme | 3 years | | Comparison of geometric mean of atazanavir Ctau with healthy adult population | To compare atazanavir Ctau with that of typical healthy adults treated with atazanavir-based ART who enter a dose escalation study of ATV/r + RIF as WP2 of the VirTUAL programme | 3 years |

Ritonavir, Atazanavir Sulfate, HIV Protease Inhibitors, Viral Protease Inhibitors, Protease Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Anti-HIV Agents, Anti-Retroviral Agents, Antiviral Agents, Anti-Infective Agents, Cytochrome P-450 CYP3A Inhibitors, Cytochrome P-450 Enzyme Inhibitors

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Children <5 years<br>Children under the age of 5 years who are receiving atazanavir as part of clinical care | Drug: Atazanavir 250 mg / ritonavir 80 mg<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care. This dose of 250/ 80 is for participants weighing between 15 and 25 Kg<br>| | Children 6-11<br>Children aged 6-11 years who are receiving atazanavir as part of clinical care | Drug: Atazanavir 250 mg / ritonavir 80 mg<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care. This dose of 250/ 80 is for participants weighing between 15 and 25 Kg<br>| | Adolescents 12-17<br>Adolescents aged 12-17 years who are receiving atazanavir as part of clinical care | Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care<br>| | Pregnant women<br>Women who are at least 20 weeks gestation, who are receiving atazanavir as part of clinical care | Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care<br>| | BMI < 18.5<br>Adults with a BMI of <18.5 kg/m2 who are receiving atazanavir as part of clinical care | Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care<br>| | BMI >30<br>Adults with a BMI of >30 kg/m2 who are receiving atazanavir as part of clinical care | Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care<br>|

Pharmacokinetics of Atazanavir in Special Populations Study Overview ================= Brief Summary ----------------- The lack of data relating to the DDI between ATV and RIF is a major limitation to the use of ATV in patients who require treatment for TB. The VirTUAL Workpackage 2 will explore the necessary dose escalation required to overcome this interaction in non-pregnant HIV-infected adults who are virologically suppressed on bPI-based ART, and who are administered RIF as a study drug, not as part of a full TB treatment regimen. As the specific objective of WP2 is to define the dose of ATV, participants taking an alternative bPI will be transitioned to ATV for the duration of that study. However, to extrapolate the results of this study to special populations such as pregnant and postpartum women, children and adolescents and those with other 'special' characteristics such as obesity (BMI >30 Kg/m2) or malnutrition (BMI <18.5 Kg/m2) we propose to undertake sparse sampling for pharmacokinetic analysis from individuals who require ATV-based ART for their clinical care. Sparse PK data will be obtained opportunistically from participants in the 'special populations' defined above who are receiving ATV as part of their routine clinical care. Subjects will be identified from clinics including the Joint Clinical Research Center (JCRC) and Infectious Diseases Institute (IDI), Kampala, and from sites including Groote Schuur Hospital and Gugulethu Community Health Centre, Cape Town. The ATV/r data from special populations will enable validation and refinement of both the PBPK model (WP1) and the pop-PK models (WP4) of the VirTUAL consortium. Detailed Description ----------------- Overview of VirTUAL Consortium Through the VirTUAL Consortium, the investigators aim to define the optimal use of second-line ART regimens in vulnerable populations with TB co-infection. The primary objective is to 'to determine the optimal dose of boosted atazanavir (ATV/r) when used in combination with RIF-based TB treatment in children, adolescents and pregnant or breastfeeding women.' The results from this protocol (VirTUAL WP5) will be considered in the context of the full research programme. This can be summarised as follows: Physiologically-based pharmacokinetic (PBPK) modelling will be developed to understand bPI and RIF Drug-Drug Interactions (DDIs), identifying potential dosing strategies to overcome these in adults and special populations (WP1). This data will inform clinical pharmacokinetic studies exploring the necessary dose escalation of ATV/r, including in the context of high-dose RIF, performed in Kampala (WP2). Intracellular pharmacokinetics will further characterise the DDI (WP3). PBPK and population pharmacokinetics (pop-PK) modelling will be integrated enabling extrapolation to special populations (WP4), and sparse data collection from such populations receiving different combinations of second-line ART and/or TB treatment in Kampala and Cape Town will validate and refine these models (WP5). Capacity building focussing on equipping African scientists with the tools to efficiently define drug dosing in complex populations (WP6), communication and stakeholder engagement (WP7) will increase the application of this methodology to other priority research into pharmacokinetics in special populations. This protocol describes the sparse pharmacokinetic sampling component which forms Workpackage 5 (WP5) of this research programme. The dose-escalation study (WP2) is an interventional trial which will be conducted in 28 healthy, virologically suppressed volunteers who are on ATV-based second-line ART, are aged over 18, have a normal BMI and are not pregnant or breastfeeding, and which will take place at JCRC, Kampala, Uganda. This study is anticipated to commence in mid-2019, and will explore in detail the changes in pharmacokinetics of ATV/r in both plasma and within cells which take place when rifampicin is co-administered, and will evaluate the necessary dose adjustment which is required to concurrently administer ATV/r with rifampicin-based TB treatment. WP2 will generate intensive data on these 28 well characterized individuals who do not have 'special' characteristics. However, there is a paucity of data on ATV/r disposition in patients who are typically excluded from clinical trials, and therefore the observational data from WP5 will be collected from individuals who fall into the listed categories of special populations and who are being treated with ATV/r for their own health. Data from either WP2 or WP5 alone will be amenable to pharmacometric analysis and bring value, but the combined modelling approach using both sets of data in a combined model will allow the most comprehensive evaluation of ATV/r disposition in the wider population, and will enable projections of dosing recommendations for the special populations who require concurrent treatment for TB whilst receiving ATV/r-based ART. Individuals will be identified at routine clinic appointments. They (or their guardians) will be asked to keep a detailed record of dosing times for three to five days prior to their study appointment at which sampling will be performed. If they take their medication in the morning, they will be asked to bring the medication to clinic for observation of dosing. Repeat sampling at subsequent appointments will enable assessment of both between and within-individual variability, for example during periods of rapid childhood growth or during pregnancy and transition back to non-pregnant physiological state. It is aimed to obtain 20 sparse PK profiles in each of the following groups (pregnant, child <5, child 6-11, adolescent 12-18, obese (BMI >30 Kg/m2), malnourished (BMI <18.5 Kg/m2)), with each individual contributing 4 samples per PK visit, and possibly followed up longitudinally during the study (each individual may attend for a maximum of three study visits). Therefore there will be between 7 (6 participants being sampled on 3 occasions and a final participant sampled on 2 occasions) and 20 (if each participant was only sampled on a single occasion) individual participants per group to generate the 20 sampling 'occasions', with a total number of participants across the six groups included in the study of between 42 and 120. This will provide an essential clinical dataset to inform the pop-PK modelling approach and validate the PBPK simulations, describing exposure and pharmacokinetic variability in the populations of interest. The data from this work package will be pooled with the data from the study in volunteers and jointly analysed using PK modelling. Differences in the PK parameters for each of the groups will be investigated. There exist no peer-reviewed published data regarding the transfer of ATV/r into breast milk. Therefore, among women who are enrolled during pregnancy and followed into the postpartum phase, paired breast milk samples will be obtained at the same time as plasma samples. Official Title ----------------- Investigation of the Pharmacokinetics of Atazanavir in Pregnant Women, Individuals at Extremes of BMI, Children, and Adolescents: An Observational Study Nested Within the VirTUAL Consortium Conditions ----------------- HIV/AIDS, Tuberculosis Intervention / Treatment ----------------- * Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily * Drug: Atazanavir 250 mg / ritonavir 80 mg Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Evidence of a personally signed and dated informed consent document indicating that the participant (or a legal representative) has been informed of all pertinent aspects of the study. In a child aged ≥7 years (South Africa) or aged ≥8 years (Uganda), evidence of assent to participate Participants who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures. HIV-infected, receiving ATV-based ART treatment OR HIV-infected receiving second-line ART with concurrent rifamycin-based TB treatment Participant is within one of the target populations: Pregnant (>20 weeks) Body mass index >30 or <18.5 Kg/m2 Child or adolescent aged <18 years Exclusion Criteria: Medical, psychiatric or obstetric condition that might affect participation in the stuy based on investigator judgement Dissent from a minor For pregnant women in Uganda, where the husband is reasonably involved, paternal objection Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Children <5 years<br>Children under the age of 5 years who are receiving atazanavir as part of clinical care | Drug: Atazanavir 250 mg / ritonavir 80 mg<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care. This dose of 250/ 80 is for participants weighing between 15 and 25 Kg<br>| | Children 6-11<br>Children aged 6-11 years who are receiving atazanavir as part of clinical care | Drug: Atazanavir 250 mg / ritonavir 80 mg<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care. This dose of 250/ 80 is for participants weighing between 15 and 25 Kg<br>| | Adolescents 12-17<br>Adolescents aged 12-17 years who are receiving atazanavir as part of clinical care | Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care<br>| | Pregnant women<br>Women who are at least 20 weeks gestation, who are receiving atazanavir as part of clinical care | Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care<br>| | BMI < 18.5<br>Adults with a BMI of <18.5 kg/m2 who are receiving atazanavir as part of clinical care | Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care<br>| | BMI >30<br>Adults with a BMI of >30 kg/m2 who are receiving atazanavir as part of clinical care | Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily<br>* There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Atazanavir Cmax | To describe the maximum concentration of atazanavir reached after dosing in the different groups | 3 years | | Atazanavir AUC0-24 | To describe the area under the concentration-time curve from 0 to 24 hours after dosing in the different groups | 3 years | | Atazanavir Ctau | To describe the trough concentration of atazanavir after dosing in the different study groups | 3 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Comparison of geometric mean of atazanavir Cmax with healthy adult population | To compare atazanavir Cmax with typical healthy individuals treated with atazanavir who enter a dose escalation study of ATV/r + RIF as WP2 of the VirTUAL programme | 3 years | | Comparison of geometric mean of atazanavir AUC0-24 with healthy adult population | To compare atazanavir AUC0-24 with that of typical healthy adults treated with atazanavir-based ART who enter a dose escalation study of ATV/r + RIF as WP2 of the VirTUAL programme | 3 years | | Comparison of geometric mean of atazanavir Ctau with healthy adult population | To compare atazanavir Ctau with that of typical healthy adults treated with atazanavir-based ART who enter a dose escalation study of ATV/r + RIF as WP2 of the VirTUAL programme | 3 years |

NCT00388076

Pazopanib (VOTRIENT) Plus Paclitaxel (TAXOL), Pazopanib Plus Paclitaxel (TAXOL) Plus Carboplatin (PARAPLATIN), and Pazopanib Plus Paclitaxel (TAXOL) Plus Lapatinib (TYKERB)

Pazopanib will be given with TAXOL in one part, in another part pazopanib will be given with TAXOL and PARAPLATIN, and in a third part pazopanib will be given with TAXOL and lapatinib (patients separated in each part). Toxicity monitoring will enable us to find the largest dose of pazopanib daily that can be safely given in combination with the chemotherapy agents TAXOL and PARAPLATIN, and with lapatinib, as well as what side effects are likely to manifest when these agents are given together and whether the combination of pazopanib with chemotherapy, helps to treat different types of cancer. Another objective is to find out how much pazopanib, TAXOL, PARAPLATIN and lapatinib are in the blood at specific times after the agents are given. Collecting the blood samples requires that the patients remain in the vicinity of the clinic overnight on 2 occasions.

A Phase I, Open-Label, Study of the Safety, Tolerability, and Pharmacokinetics of Pazopanib in Combination With Paclitaxel on a Weekly Schedule for Three Consecutive Weeks of a 28-Day Cycle, Paclitaxel and Carboplatin on an Every 21 Days Schedule and Lapatinib and Paclitaxel on a Weekly Schedule for Three Consecutive Weeks of a 28- Day Cycle

Neoplasms, Breast

* Drug: Pazopanib * Drug: Lapatinib * Drug: paclitaxel * Drug: carboplatin

Inclusion criteria:~Confirmed diagnosis of cancer, except cervical cancer~Eastern Cooperative Oncology Group performance Status of 0 or 1~Peripheral neuropathy of Grade 1 or less~Adequate bone marrow function (absolute neutrophils, platelets and hemoglobin levels as per protocol)~Adequate renal function as per protocol~Urine creatinine ratio as per protocol~Adequate hepatic function as per protocol~Coagulation tests as per protocol~Male of female at least 18 years of age~A woman is eligible to enter and participate in the study if she is of:~Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any woman who:~Has had a hysterectomy,~Has had a bilateral oophorectomy (ovariectomy),~Has had a bilateral tubal ligation,~Is post-menopausal (total cessation of menses for at least 1 year)~Childbearing potential, has a negative serum or urine pregnancy test at screening, and agrees to one of the following:~An intrauterine device (IUD) with a documented failure rate of less than 1% per year.~Vasectomized partner who is sterile prior to the patient's entry and is the sole sexual partner for that woman.~Complete abstinence from sexual intercourse for 14 days before exposure to investigation product, throughout the clinical trial, and for at least 21 days after the last dose of investigational product.~Double-barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR male condom and diaphragm.~Predicted life expectancy of at least 12 weeks~Written informed consent~Able to swallow and retain oral medications.~Exclusion criteria:~No more than 3 prior lines of cytotoxic chemotherapy for metastatic disease are allowed.~No major surgery, nor cytotoxic chemotherapy, investigational agents, or radiotherapy within the last 28 days and subject must have recovered fully from whatever their last treatment was at the time of enrollment.~Women who are pregnant or breast feeding are not eligible to enroll.~Cannot have poorly controlled hypertension.~Cannot have corrected QT (QTc) prolongation~Cannot have Class III or IV heart failure as defined by the New York Heart Association functional classification system.~Cannot have arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the last 3 months.~Cannot use of therapeutic warfarin.~Cannot have history of bleeding (hemoptysis, hematuria, GI blood loss, epistaxis, or others with greater than Grade 1 according to CTC Criteria) within six weeks prior to beginning therapy or any clinical indications of current active bleeding or bleeding diathesis.~Cannot have history or clinical evidence of CNS metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 2 months prior to beginning study treatment.~Cannot have any serious and/or unstable pre-existing medical, psychiatric, or other condition (including laboratory abnormalities) that could interfere with patient safety or obtaining consent.~Cannot have history of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of pazopanib, paclitaxel, or carboplatin. Has any unresolved bowel obstruction or diarrhea. Has clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding including, but not limited to:~active peptic ulcer disease,~known intraluminal metastatic lesion(s) with suspected bleeding,~inflammatory bowel disease including ulcerative colitis, or other GI conditions with increased risk of perforation,~history of abdominal fistula, GI perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.~Subject must not have psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.~Subject must not take any specifically prohibited medication specified in the protocol during the study or requires any of these medications during treatment with pazopanib.~Subject must not have clinical history, current alcohol or illicit drug use which, in the judgment of the Investigator, would interfere with the patient's ability to comply with the dosing schedule and protocol-specified evaluations.~Subject must not be allergic to either TAXOL or PARAPLATIN, or any other taxane or platinum containing compound.~Subject must not have a current diagnosis of cervical cancer.~Subject must not have known endobronchial metastasis or involvement of large pulmonary vessel(s) by tumor.

18 Years

All

No

Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Adverse Effects, Laboratory parameters | | before and after taking the study medications. |

| Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Blood samples | | over a 24 hour period | | Tumors | | will be measured at routine intervals throughout (e.g. by CT scan). |

carboplatin, lapatinib, TAXOL, PARAPLATIN, paclitaxel, TYKERB, Pazopanib

Paclitaxel, Carboplatin, Lapatinib, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action, Protein Kinase Inhibitors, Enzyme Inhibitors

| Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Part 1<br>pazopanib and paclitaxel | Drug: Pazopanib<br>* pazopanib in combination with paclitaxel in Part 1, paclitaxel and carboplatin in Part 2, and paclitaxel and lapatinib in Part 3<br>Drug: paclitaxel<br>* in combination with pazopanib<br>* Other names: TAXOL;| | Experimental: Part 2<br>pazopanib, paclitaxel, and carboplatin | Drug: Pazopanib<br>* pazopanib in combination with paclitaxel in Part 1, paclitaxel and carboplatin in Part 2, and paclitaxel and lapatinib in Part 3<br>Drug: paclitaxel<br>* in combination with pazopanib<br>* Other names: TAXOL;Drug: carboplatin<br>* in combination with pazopanib<br>* Other names: PARAPLATIN;| | Experimental: Part 3<br>pazopanib, paclitaxel, and lapatinib | Drug: Pazopanib<br>* pazopanib in combination with paclitaxel in Part 1, paclitaxel and carboplatin in Part 2, and paclitaxel and lapatinib in Part 3<br>Drug: Lapatinib<br>* Lapatinib in combination with pazopanib and paclitaxel in Part 3<br>Drug: paclitaxel<br>* in combination with pazopanib<br>* Other names: TAXOL;|

Pazopanib (VOTRIENT) Plus Paclitaxel (TAXOL), Pazopanib Plus Paclitaxel (TAXOL) Plus Carboplatin (PARAPLATIN), and Pazopanib Plus Paclitaxel (TAXOL) Plus Lapatinib (TYKERB) Study Overview ================= Brief Summary ----------------- Pazopanib will be given with TAXOL in one part, in another part pazopanib will be given with TAXOL and PARAPLATIN, and in a third part pazopanib will be given with TAXOL and lapatinib (patients separated in each part). Toxicity monitoring will enable us to find the largest dose of pazopanib daily that can be safely given in combination with the chemotherapy agents TAXOL and PARAPLATIN, and with lapatinib, as well as what side effects are likely to manifest when these agents are given together and whether the combination of pazopanib with chemotherapy, helps to treat different types of cancer. Another objective is to find out how much pazopanib, TAXOL, PARAPLATIN and lapatinib are in the blood at specific times after the agents are given. Collecting the blood samples requires that the patients remain in the vicinity of the clinic overnight on 2 occasions. Official Title ----------------- A Phase I, Open-Label, Study of the Safety, Tolerability, and Pharmacokinetics of Pazopanib in Combination With Paclitaxel on a Weekly Schedule for Three Consecutive Weeks of a 28-Day Cycle, Paclitaxel and Carboplatin on an Every 21 Days Schedule and Lapatinib and Paclitaxel on a Weekly Schedule for Three Consecutive Weeks of a 28- Day Cycle Conditions ----------------- Neoplasms, Breast Intervention / Treatment ----------------- * Drug: Pazopanib * Drug: Lapatinib * Drug: paclitaxel * Drug: carboplatin Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria: Confirmed diagnosis of cancer, except cervical cancer Eastern Cooperative Oncology Group performance Status of 0 or 1 Peripheral neuropathy of Grade 1 or less Adequate bone marrow function (absolute neutrophils, platelets and hemoglobin levels as per protocol) Adequate renal function as per protocol Urine creatinine ratio as per protocol Adequate hepatic function as per protocol Coagulation tests as per protocol Male of female at least 18 years of age A woman is eligible to enter and participate in the study if she is of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any woman who: Has had a hysterectomy, Has had a bilateral oophorectomy (ovariectomy), Has had a bilateral tubal ligation, Is post-menopausal (total cessation of menses for at least 1 year) Childbearing potential, has a negative serum or urine pregnancy test at screening, and agrees to one of the following: An intrauterine device (IUD) with a documented failure rate of less than 1% per year. Vasectomized partner who is sterile prior to the patient's entry and is the sole sexual partner for that woman. Complete abstinence from sexual intercourse for 14 days before exposure to investigation product, throughout the clinical trial, and for at least 21 days after the last dose of investigational product. Double-barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR male condom and diaphragm. Predicted life expectancy of at least 12 weeks Written informed consent Able to swallow and retain oral medications. Exclusion criteria: No more than 3 prior lines of cytotoxic chemotherapy for metastatic disease are allowed. No major surgery, nor cytotoxic chemotherapy, investigational agents, or radiotherapy within the last 28 days and subject must have recovered fully from whatever their last treatment was at the time of enrollment. Women who are pregnant or breast feeding are not eligible to enroll. Cannot have poorly controlled hypertension. Cannot have corrected QT (QTc) prolongation Cannot have Class III or IV heart failure as defined by the New York Heart Association functional classification system. Cannot have arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the last 3 months. Cannot use of therapeutic warfarin. Cannot have history of bleeding (hemoptysis, hematuria, GI blood loss, epistaxis, or others with greater than Grade 1 according to CTC Criteria) within six weeks prior to beginning therapy or any clinical indications of current active bleeding or bleeding diathesis. Cannot have history or clinical evidence of CNS metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 2 months prior to beginning study treatment. Cannot have any serious and/or unstable pre-existing medical, psychiatric, or other condition (including laboratory abnormalities) that could interfere with patient safety or obtaining consent. Cannot have history of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of pazopanib, paclitaxel, or carboplatin. Has any unresolved bowel obstruction or diarrhea. Has clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding including, but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion(s) with suspected bleeding, inflammatory bowel disease including ulcerative colitis, or other GI conditions with increased risk of perforation, history of abdominal fistula, GI perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment. Subject must not have psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. Subject must not take any specifically prohibited medication specified in the protocol during the study or requires any of these medications during treatment with pazopanib. Subject must not have clinical history, current alcohol or illicit drug use which, in the judgment of the Investigator, would interfere with the patient's ability to comply with the dosing schedule and protocol-specified evaluations. Subject must not be allergic to either TAXOL or PARAPLATIN, or any other taxane or platinum containing compound. Subject must not have a current diagnosis of cervical cancer. Subject must not have known endobronchial metastasis or involvement of large pulmonary vessel(s) by tumor. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Part 1<br>pazopanib and paclitaxel | Drug: Pazopanib<br>* pazopanib in combination with paclitaxel in Part 1, paclitaxel and carboplatin in Part 2, and paclitaxel and lapatinib in Part 3<br>Drug: paclitaxel<br>* in combination with pazopanib<br>* Other names: TAXOL;| | Experimental: Part 2<br>pazopanib, paclitaxel, and carboplatin | Drug: Pazopanib<br>* pazopanib in combination with paclitaxel in Part 1, paclitaxel and carboplatin in Part 2, and paclitaxel and lapatinib in Part 3<br>Drug: paclitaxel<br>* in combination with pazopanib<br>* Other names: TAXOL;Drug: carboplatin<br>* in combination with pazopanib<br>* Other names: PARAPLATIN;| | Experimental: Part 3<br>pazopanib, paclitaxel, and lapatinib | Drug: Pazopanib<br>* pazopanib in combination with paclitaxel in Part 1, paclitaxel and carboplatin in Part 2, and paclitaxel and lapatinib in Part 3<br>Drug: Lapatinib<br>* Lapatinib in combination with pazopanib and paclitaxel in Part 3<br>Drug: paclitaxel<br>* in combination with pazopanib<br>* Other names: TAXOL;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Adverse Effects, Laboratory parameters | | before and after taking the study medications. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Blood samples | | over a 24 hour period | | Tumors | | will be measured at routine intervals throughout (e.g. by CT scan). | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- carboplatin, lapatinib, TAXOL, PARAPLATIN, paclitaxel, TYKERB, Pazopanib