Abstract
Objective:Determine the minimum dosage of alanyl-glutamine (Ala-Gln) required to improve gut integrity and growth in children at risk of environmental enteropathy (EE).Methods:This was a double-blinded randomized placebo-controlled dose-response trial. We enrolled 140 children residing in a low-income community in Fortaleza, Brazil. Participants were 2 to 60 months old and had weight-for-age (WAZ), height-for-age (HAZ), or weight-for-height (WHZ) z-scores less than −1. We randomized children to 10 days of nutritional supplementation: Ala-Gln at 3 g/day, Ala-Gln at 6 g/day, Ala-Gln at 12 g/day, or an isonitrogenous dose of glycine (Gly) placebo at 12.5 g/day. Our primary outcome was urinary lactulose-mannitol excretion testing. Secondary outcomes were anthropometry, fecal markers of inflammation, urine metabolic profiles, and malabsorption (spot fecal energy).Results:Of 140 children, 103 completed 120 days of follow-up (24% dropout). In the group receiving the highest dose of Ala-Gln, we detected a modest improvement in urinary lactulose excretion from 0.19% on day 1 to 0.17% on day 10 (P=0.05). We observed significant but transient improvements in WHZ at day 10 in 2 Ala-Gln groups, and in WHZ and WAZ in all Ala-Gln groups at day 30. We detected no effects on fecal inflammatory markers, diarrheal morbidity, or urine metabolic profiles; but did observe modest reductions in fecal energy and fecal lactoferrin in participants receiving Ala-Gln.Conclusions:Intermediate dose Ala-Gln promotes short-term improvement in gut integrity and ponderal growth in children at risk of EE. Lower doses produced improvements in ponderal growth in the absence of enhanced gut integrity.
Highlights
MethodsStudy Type and LocationThe IMAGINE Trial (NCT01832636) was a prospective randomized double-blinded placebo-controlled dose-response trial conducted in the Parque Universitario urban community in Fortaleza, Brazil
There were no significant differences between groups in age, sex, anthropometric z-scores, diarrheal history, or ULM ratios, which were within the range of values for healthy children in this community (Table 1) [12]
Fecal markers of inflammation and fecal cytokines were within the range previously reported in healthy controls, fecal calorimetry was slightly elevated compared with previously reported normal values with M (SD) of 5143.2 (505.5) [16]
Summary
Study Type and LocationThe IMAGINE Trial (NCT01832636) was a prospective randomized double-blinded placebo-controlled dose-response trial conducted in the Parque Universitario urban community in Fortaleza, Brazil. The protocol and consent forms for this study were approved by the institutional review board at the Federal University of Ceara, Fortaleza, Brazil, and at the Cincinnati Children’s Hospital Medical Center. Children ages 2 to 60 months old residing in the Parque Universitario neighborhood with HAZ, WAZ, or WHZ less than or equal to À1 were considered for inclusion. Those with clinical evidence of systemic disease, fever >38.8 8C, or antibiotic use at the time of screening were excluded, as were children with history of exclusive breast-feeding, chronic disease, previous participation in an intervention study, or those unable to ingest and retain nutritional supplements. A total of 140 participants were enrolled between October 2013 and December 2015, and were followed for 120 days (Fig. 1)
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