Does Intermittent Nutrition Enterally Normalise hormonal and metabolic responses to feeding in critically ill adults? A protocol for the DINE-Normal proof-of-concept randomised parallel group study

Abstract

ABSTRACTIntroductionOver half of patients who spend >48 hours in the intensive care unit (ICU) are fed via a nasogastric (NG) tube. Current guidance recommends continuous delivery of feed throughout the day and night. Emerging evidence from healthy human studies shows that NG feeding in an intermittent pattern (rather than continuous) promotes phasic hormonal, digestive and metabolic responses that are important for effective nutrition. It is not yet known whether this will translate to the critically ill population. Here we present the protocol for a proof-of-concept study comparing diurnal intermittent versus continuous feeding for patients in the intensive care unit.Methods and AnalysisThe study is a single-centre, prospective, randomised, open-label trial comparing intermittent enteral nutrition with the current standard practice of continuous enteral feeding. It aims to recruit participants (n=30) needing enteral nutrition via an NG tube for >24 hours who will be randomised to a diurnal intermittent or a continuous feeding regime with equivalent nutritional value. The primary outcome is peak plasma insulin / c-peptide within 3 hours of delivering the morning bolus feed on the second study day, compared to that seen in the continuous feed delivery group at the same timepoint. Secondary outcomes include feasibility, tolerability, efficacy and metabolic / hormonal profiles.Ethics and DisseminationThis trial has been registered prospectively with the Clinical Trials Registry (clinicaltrials.govNCT06115044). We obtained ethical approval from the Wales Research Ethics Committee 3 prior to data collection (reference 23/WA/0297). We will publish the results of this study in an open-access peer-reviewed journal.Strengths and Limitations of this StudyHaving studied metabolic consequences of intermittent versus continuous nasogastric feed delivery in healthy volunteers, our trial team is well positioned to explore the direct ‘bench-to-bedside’ exploration of the interaction between critical illness and the mode of feed delivery through detailed profiling of metabolic hormones.The intermittent feeding intervention in this study has been carefully considered to replicate diurnal rhythms, with sufficient fasting between feeding cycles, to allow us to capture a difference in response to continuous feeding if one exists.The findings of this study will inform the feasibility and design of a trial of the effectiveness of intermittent diurnal nutrition in critically ill adults.This is an open-label, single-centre study, which may bias the interpretation and limit the generalisability of the results.