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

Abstract

AbstractBackgroundChildren 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.ObjectivesWe propose that legume-based feeds rich in fermentable carbohydrates will promote better gut health and improve overall outcomes.MethodsWe 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 novodevelopment of diarrhoea, time to diarrhoea and oedema resolution.FindingsIncrease 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.ConclusionFurther refinement of legume feeds and clinical trials are warrented given the poor outcomes in children with severe malnutrition.Trial registrationISRCTN 10309022.FundingConfidence in Concepts – Joint Translational Fund 2017(Imperial College, London)