Abstract
Background: Childhood undernutrition is a major public health concern that needs special attention to achieve 2025 global nutrition targets. Moderate acute malnutrition (MAM), manifest as wasting (low weight-for-height), affects 33 million children under 5, yet there are currently no global guidelines for its treatment. We recently performed a randomized-controlled clinical study of a microbiota-directed complementary food formulation (MDCF-2) in 12-18-month-old Bangladeshi children with MAM. The results revealed that MDCF-2, freshly prepared each day, produced a significantly greater improvement in ponderal growth than a standard ready-to-use supplementary food (RUSF), an effect that is associated with repair of the disrupted gut microbial community development that occurs in children with MAM. To test the generalizability of these results in acutely malnourished children at other sites, there is a pressing need for a packaged, shelf-stable, organoleptically-acceptable formulation that is bioequivalent to MDCF-2. This report describes the protocol for a clinical study to evaluate candidate formulations designed to meet these criteria. Methods: A randomized single-blind study will be conducted in 8-12-month-old Bangladeshi children with MAM to compare the efficacy of alternative shelf-stable MDCF prototypes versus the current MDCF-2 formulation that is produced fresh each day. V4-16S rDNA amplicon and shotgun sequencing datasets will be generated from faecal DNA samples collected from each child enrolled in each group prior to, during, and after treatment to determine the abundances of MDCF-2-responsive bacterial taxa. Efficacy will be assessed by quantifying the change in representation of MDCF-2-responsive gut bacterial taxa after 4-weeks of treatment with freshly prepared MDCF-2 compared to their changes in abundance after treatment with the prototype MDCFs. Equivalence will be defined as the absence of a statistically significant difference, after 4-weeks of treatment, in the representation of faecal bacterial taxa associated with the response to MDCF-2 in participants receiving a test MDCF. Discussion: This trial aims to establish acceptability and equivalence with respect to microbiota repair, of scalable, shelf-stable formulations of MDCF-2 in 8-12-month-old Bangladeshi children with moderate acute malnutrition. Trial registration: ClinicalTrials.gov (NCT05094024). The trial has been registered before starting enrolment on 23 October 2021.
Original language | English |
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Article number | 385 |
Number of pages | 9 |
Journal | Bmc Pediatrics |
Volume | 22 |
DOIs | |
Publication status | Published - Jul 2022 |
Publication type | A1 Journal article-refereed |
Funding
This study is funded by the Bill & Melinda Gates Foundation, INV-016370. The study protocol was primarily reviewed by the donor organization prior to external review. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank all the participants, their parents, and caregivers as well as the study staff for their valuable contributions in the study. icddr,b is also grateful to the Government of Bangladesh, Canada, Sweden, and the UK for providing unrestricted support.
Keywords
- Gut Microbiota
- Microbiota Directed Complementary Food
- Moderate Acute Malnutrition
Publication forum classification
- Publication forum level 1
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health