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.

Introduction: Over 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 Analysis: The 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 Dissemination: This trial has been registered prospectively with the Clinical Trials Registry (clinicaltrials.gov - NCT06115044). 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.