Modifying gut integrity and microbiome in children with severe acute malnutrition using legume-based feeds (MIMBLE II): A Phase II trial

Background Children hospitalised with severe malnutrition (SM) have high mortality and relapse/readmission rates. Current milk-based formulations targets restoring ponderal growth but not modification of gut barrier integrety or microbiome which increase risk of gram-negative sepsis and poor outcomes. Objectives We propose that legume-based feeds rich in fermentable carbohydrates will promote better gut health and improve overall outcomes. Methods We conducted at Mbale Regional Referral Hospital, Uganda an open-label Phase II trial involving 160 Ugandan children with SM (mid-upper arm circumference (MUAC) <11.5cm and/or nutritional oedema). Children were randomised to a lactose-free, chickpea-enriched legume paste feed (LF) (n=80) versus WHO standard F75/F100 feeds (n=80). Co-primary outcomes were change in MUAC and mortality to Day 90. Secondary outcomes included weight gain (>5 g/kg/day), de novo development of diarrhoea, time to diarrhoea and oedema resolution. Findings Increase in Day 90 MUAC was similar in LF and WHO arms (1.1 cm (interquatile range.IQR 1.1) vs 1.4cm (IQR 1.40) p=0.09. Day 90 mortality was similar 11/80 (13.8%) vs 12/80 (15%) respectively OR 0.91 (0.40 -2.07) p=0.83. There were no differences in any of the other secondary outcomes. Owing to initial poor palatability of the legume feed 10 children switched to WHO feeds. Per protocol analysis indicated a non-significant trend to lower Day 90 mortality and readmission rates in the legume feed (6/60: (10%) and (2/60: 3%) vs WHO feeds (12/71: 17.5%) and (4/71: 6%) respectively. Conclusion Further refinement of legume feeds and clinical trials are warrented given the poor outcomes in children with severe malnutrition. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ISRCTN 10309022 ### Clinical Protocols ### Funding Statement The study was funded by Confidence in Concepts Joint Translational Fund 2017 (Imperial College, London) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committees of Imperial College London, UK (17IC4146) and Mbale Hospital Research Ethics Committee, Uganda (019/2018) approved the protocol. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors