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Effectiveness of proprioceptive training versus conventional exercises on postural sway in patients with early knee osteoarthritis – A randomized controlled trial protocol

Highlights • Knee OA being a major cause of disability, there is a growing interest in Early OA.• Altered Proprioception cause defect in tissues, worsening balance and injury’s.• Early cartilage defects due to injuries are reversible.• Early identification and problem targeted treatment should be the primary goal.


Introduction
Knee osteoarthritis (OA) is one of the major causes of pain and physical disability in older adults [1]. It has been stated that osteoarthritis affects 33.6% of the population over 65 years old and surprisingly, 13.9% of the population over 25 years old [2]. Approximately 80% of population in India who claim to have knee pain show signs of OA, of which, 20% report incapability in daily activities [3]. considering this it has been suggests that primary prevention of knee OA should become a major aim of health care [1].
Recent literature shows a growing interest in 'early osteoarthritis' (EOA) [4,5]. EOA could be defined as the clinical recurrence of pain and discomfort of the knee, short periods of stiffness, with in between long periods of very little clinical manifestations [2]. There is ample evidence that anterior cruciate ligament rupture, meniscal tear, smoking, vitamin D deficiency, physical inactivity, muscle weakness, leptin, dietary fatty acid intake and mechanical/neuromuscular changes are some of the risk factors associated with EOA [2,4].
Neuromuscular changes for instance, decreased strength and proprioceptive accuracy of the knee extensors in people with EOA had increased postural sway during single leg stance, which could be associated with altered muscle activation patterns, altered proprioception, sluggish reaction time, valgus and varus instability at the knee [6,7].
Proprioception is the conscious and unconscious recognition or perception of joint position. Proprioception, activates and regulates muscles function which stabilize the joint and produce controlled https://doi.org/10.1016/j.isjp.2020.09.002 2468-3574/Ó 2020 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). joint movements [8]. Pain, inflammation or mechanical stress may contribute to proprioceptive deficiency [9]. Proprioceptive deficiency have shown to cause building up of unusual pressure in the surrounding tissue which might cause abnormal joint position sense and could increase the incidence of injury [9]. It has been claimed that early cartilage defects and other soft tissue injury are reversible, particularly in younger people [6]. Therefore it is important to recognize individuals presenting with early symptoms [5].
Conservative management for EOA include nonpharmacological interventions (lifestyle modifications, exercise therapy, physical therapy, dietary supplements), pharmacological therapies (NSAIDS, glucosamine and chondroitin) [2,10]. Exercise therapy including isometric and isotonic exercises for quadriceps, cycling on a static cycle [11]. Exercise helps to decrease pain, improve health status and physical function and prevent the condition from progressing [10].
Under normal loading conditions, weight bearing joints have been found to experience forces as high as 10 times body weight [12], considering this we hypothesize that some of the exercises though it strengthens the muscles, it might adversely affect the joint.
Abnormal mechanical loading of the articular cartilage can aggravate pain and possibly lead to cartilage destruction. Proprioceptive training on the other hand strengthens the proprioceptive system in a more static activity and less impactful when compared to routine exercises. In addition to the above, the data to support the use of proprioceptive training in early OA is limited. With this background the current study aims to investigate the effect of proprioceptive training on postural sway, joint position sense, muscle function, pain and functional outcome in patients with EOA and to determine the effectiveness of proprioceptive training versus conventional exercises in patients with EOA.

Trial design
We are conducting a single blinded, randomized controlled trial among adult participants with early osteoarthritis. This randomized controlled trial has received ethical approval from Institutional Ethics Committee of Kasturba Medical College, Mangalore. Manipal Academy of Higher Education (MAHE). (Ref -IEC KMC MLR 08-18/171). This Trial is also registered with Clinical Trials Registry -India (CTRI), URL-ctri.nic.in. The registration number for the trial is CTRI/2019/01/017049.
The study has already commenced in the mid-2019, will continue for the next 2 years and will be completed at Department of Physiotherapy and Department of Sports injury and Joint replacement at Kasturba Medical College Hospitals, Ambedkar circle, Mangaluru. The trial will be stated as per SPIRIT and CONSORT guidelines. Figure 1 demostrates outline of the study.

Participants
Based on sample size calculation following our pilot study, we plan to enroll 100 participants in the study, before enrollment in to the study each participant will providing their written consent, which will be obtained by the primary investigator. Participants will be enrolled based on inclusion and exclusion criteria. Considering a attrition rate of 20%, we expect up to 80 participants to complete the study, with 40 participants in each group. However, if the dropouts are beyond 20%, an intention to treat analysis instead of per protocol analysis will be undertaken. Inclusion and exclusion criteria are mentioned in Table 1.

Randomization/allocation/blinding
Upon enrollment into the study, the patients will be allocated to groups, i.e. conventional and interventional group., for the same sequence generation will be done by block randomization and allocation concealment will be done using sealed opaque envelopes. Following the allocation of the groups, an independent assessor who is blinded to the intervention, having adequate knowledge about the assessment tools will record the outcome measures. Data will be recorded at baseline, once every week till the completion of intervention and at the third month. Both the groups will receive 12 sessions of treatment, 3 sessions per week, spanning over 4 weeks. Post which the participants will be advised to carry out home exercise programme for the next two months.

Follow-up
Patients will also be asked to maintain a diary to keep a track of theirs exercises sessions. The primary investigator will give a reminder call about the exercise to the patients once in every 15 days. There will be a clinical review at 8th week, followed by a final follow-up at 12th week. After inclusion, patients with acute flare-up of symptoms with a need of analgesics for more than 5 days and/or intercurrent illness lasting for more than 7 to 10 days will no longer be part of the study.

Interventions
Both the conventional and interventional group would have treatment without outward apparent differences. The time needed for each session would be similar. Participants will receive interferential therapy for 20 minutes for relieving possible exercise induce pain, irrespective of their study group at the end of the exercise session [13]. The intervention will be given by a qualified Physiotherapist.

Postural sway
The participants will be asked to stand on the force-plate and maintain that posture as stable as possible. Data will be collected in both eye open and closed scenario, during eye open they will be asked to fix their view on a spot which will be marked on the wall at a distance of 3 m. Test will be repeated 3 times for 30sec each with a rest period of 1 min between each attempt [21].
Following recording the data center of pressure excursion (COPE) area will be determined by creating a rectangular area defined by maximum limit of excursion in each direction. The area on the graph will be calculated using grid method, where each grid square is 1 cm. For calculation following equation will be used ''Area = Width Â Height", and it value will be expressed in 'cm 2 '. Table 1 Inclusion and Exclusion criteria.

Inclusion criteria
1. Age ! 20 and < 45 years 2. Satisfying 4 out of 6 clinical symptoms criteria i;e Recurrent pain, pain following a duration of rest, discomfort at rest, swelling, instability, reduced range of motion. 3. Subject with clinically and radiological confirmed diagnosis of EOA by an Orthopaedician or a Rheumatologist. These parameters will be analyzed using artificial intelligence (AI) for better understanding of the outcome.

Joint position sense
Active joint position sense (JPS) will be testing with the help of digital goniometer. Subjects will be examined in supine position with lower limb exposed, and eyes closed. The fulcrum of the goniometer will be placed over later knee joint line. At completer extension, the goniometer and the starting position will be set to be 0°. The target angles will be as 15°, 30°, 45°and 60°. The angle of concern will be instructed to the subjects twice before the measurement. Then, the subjects will be instructed to find the correct angle, with six time repetitions. The deviations of the average of the six measurements from the target angle were recorded for all angles. [9] Secondary outcomes:

Muscle strength
Patient will be asked to sit on an adjustable examination couch in a high sitting position (hip and knee at 90-degree flexion), with a gap of 1-2 cm between the back of knee joint and the couch. The height of the couch should be such that the there is a gap of at least 10 cm between the patients feet and the floor. Patient has to hold the side edge of the couch for support and perform a maximum voluntary isometric contraction with a hold of 5sec.
For knee extensor strength assessment, the dynamometer will be kept on anterior part of leg, just above the talotibial joint line and for knee flexor strength assessment, the dynamometer will be placed on the posterior part of leg above malleolar level.
Test will be repeated 3 times with 5 sec hold and 60 sec rest period between each test. [18] 4. VAS It is a 10 cm line (i.e. 100 mm), where the patient will be asked to mark a point on the line representing their pain intensity. Pain intensity is categorized as no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm) and severe pain (75-100 mm).

Functional outcome measure (KOOS)
KOOS is an instrument specific to the knee joint, developed to evaluate the patient's viewpoint about their problems related to the knee joint. It helps to assess short and long-term consequences simultaneously. It consists of 42 items which is divided in 5 subscales which consists of pain, other symptoms (ADL), sport and recreational activity (sport/rec), and Quality of life related to knee (QOL). [19] 2.9. Data analysis Pilot study: We initially conducted a pitot study, for which 12 participants were recruited based on the inclusion and exclusion criteria mentioned in Table 1. Six participants received conventional management, and the other 6 participants received proprioceptive training. Each participant was followed for 3 months, with 2 dropouts. The outcome measure analyzed were COPE (center of pressure excursion) for postural sway, joint position sense for proprioception, Hand held dynameters for muscle strength, VAS for pain and KOOS (Knee Injury and Osteoarthritis Outcome Score) for quality of life. Collected data ( Table 2) were analyzed by mean, standard deviation and 2 factor ANOVA for repeated measure, followed by Bonferroni post hoc analysis. p < 0.05 was considered to be significant. Based on the results obtained from the pilot study, the sample size for the current study was calculated.
Power calculation According to data from our preliminary pilot study (Table 2), at 90% power, n = 39 subjects in each group was estimated, Considering dropout rate of approximately 20%, a total of 100 participants will be recruited.
Statistical analysis Data Collected will be analyzed by mean, SD and 2 factor ANOVA for repeated measure, followed by Bonferroni post hoc analysis. Data will be analyzed using SPSS package version 17.0, p < 0.05 will be considered as significant.
Data management Every questionnaire, screening tool, and consent will contain a separate trial no unique for each participant. All the data entry and analysis will be done using the trial no. Hard copies of the data will be kept in securely locked filling cabinets at department and only study investigators will have access to the hard copies. Moreover, Password protected computer and data bases will be used to maintain confidentiality of electronic data. In addition, the backup files for electronic data will also be maintained to prevent loss of data.
Ethics and dissemination Approval for the conduction of this study has been granted by Institutional Ethical Review Committee. Informed written consent to participate will be obtained from all participants. The findings of this study will be communicated with all the healthcare providers via Seminar, CME, scientific paper, and conference presentation.

Potential impact and significance
There is a need to conduct this RCT to better understand the outcome of the study, as the results of the pilot study revealed a promising potential with proprioceptive training. This study is also first to use Artificial Intelligence (AI) to analyze parameters derived from force plate, which could be developed as an effective monitoring tool. On the other hand, the force plate outcome can also be used as a feedback tool, the visual feedback provided by a repeated force plate assessment might help encourage patients to improve compliance and acceptance of exercise techniques.
According to recent studies open kinetic chain (OKC) exercises decreases joint proprioception and synergistic muscle activation, leading to increased shear forces and there by adversely affect the joint [20]. Proske U and Gandevia SC stated that concentric and eccentric exercise too disturbed both senses of joint position and force [21].
In study by Veena Kirthika et al. [16] and G Panics et al. [22], it was stated that proprioceptive activation exercises have a direct effect on the joint position sense, mobility and pain sensations and restoration of proprioception is essential during the rehabilitation of patients with knee OA.
As per the current guidelines of AAOS (American Academy of Orthopaedic Surgeons), persons with symptomatic knee should consider exercise therapy as a preventive non-surgical treatment strategy best before mechanical derangement sets in, postponing or avoiding early surgical procedures which are unwarranted [23]. According to previous studies, force plates have been able to pick up changes in arthritis [17]. Our pilot study too demonstrates that they are sensitive enough to early changes and relatively minor differences. There is huge potential in using these as a prognostic and monitoring tool. Furthermore use of artificial intelligence in measuring the centre of pressure plot will help objectivize the measurements for easier interpretation.
Hence we hypothesize that proprioceptive training could prevent impact loading of the joints and help to prevent progression of the injury and could improve strength and balance at the same time. Proprioceptive training could be used as an alternate to more time consuming, strenuous and impactful conventional exercises, thereby helping in reducing pain, reduce progression of the condition, better joint and muscle health and improve functional quality of patients with EOA.

Consent
Informed Consent will be obtained from the patients.

Registration of Research Studies
This Trial is also registered with Clinical Trials Registry -India (CTRI), URL-ctri.nic.in.
The registration number for the trial is CTRI/2019/01/017049

Guarantor
On behalf of all the contributors I (Ashish Prabhakar) will act as guarantor and will correspond with the journal from this point onward and I declare that all the contributors have participated towards the completion of the manuscript