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

BackgroundChildren 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 novo development 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)