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Continuous versus Intermittent Nutrition in Pediatric Intensive Care patients (ContInNuPIC): a study protocol for a randomized controlled trial (Preprint)


 UNSTRUCTURED
 Background:
‘Intermittent fasting’ is a time-restricted feeding strategy with proven health benefits in several patient populations and healthy subjects, which are based on multiple metabolic and endocrine changes. In the pediatric intensive care unit (PICU) artificial feeding is usually administered 24 hours a day, although solid evidence supporting this practice is lacking. This discards the potential benefit of fasting in this population. We hypothesize that intermittent nutrition with the focus on an overnight feeding interruption (‘intermittent fasting’), as compared with 24 hours continuous nutrition, is a feasible and safe strategy for children during critical illness with potential benefits.

Methods:
The Continuous versus Intermittent Nutrition in Pediatric Intensive Care (ContInNuPIC) study is an investigator-initiated, randomized controlled trial (RCT) in a tertiary referral PICU. Critically ill children (term newborn - 18 years), expected to stay in the PICU ≥ 48 hours and dependent on artificial nutrition, are eligible for inclusion. This study randomizes critically ill children (n=140) to a ’Continuous’ versus ‘Intermittent’ nutrition strategy. In both study groups similar daily caloric targets are prescribed. In the Continuous group (control), nutrition is administered 24 hours a day with a maximum interruption of two hours. In the Intermittent group (intervention), nutrition is interrupted during an age-dependent overnight fasting period. The study intervention lasts until admission day 14, initiation of oral intake, or discharge from the PICU, whichever comes first. The primary outcome is the difference in ketosis between the groups, under the condition of non-inferiority regarding the caloric intake. Secondary outcomes are the feeding intolerance, the proportion of severe and/or resistant hypoglycemic events and severe gastro-intestinal complications, and additional observed effects on nutritional intake, circadian rhythm and clinically relevant outcome measures of the intermittent feeding strategy as compared with continuous nutrition. 

Results:
The study was approved by the Dutch national ethical review board in February 2020. The first patient was enrolled on May 19th, 2020. By January 2022, 111 patients have been included in the study. The study is still in progress and recruitment of the last patient is expected in Q2 2022.

Discussion:
Although ‘intermittent fasting’ has been proven to have many health benefits in both animal and human studies, the feasibility and safety of such strategy in PICU setting must be investigated. This RCT will help physicians to gain more insight in the feasibility, safety and potential clinical effects of intermittent feeding with an overnight fast in critically ill children. 

Trial registration: Netherlands Trial Register: NL7877 on July 16th, 2019.
