Nutrition and Clinical Services Division, icddr,b, Dhaka, 1212, Bangladesh.
Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland.
BMC Pediatr. 2022 Jul 1;22(1):385. doi: 10.1186/s12887-022-03436-6.
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.
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.
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.
ClinicalTrials.gov (NCT05094024). The trial has been registered before starting enrolment on 23 October 2021.
儿童期营养不良是一个重大的公共卫生问题，需要特别关注，以实现 2025 年全球营养目标。中重度急性营养不良（MAM）表现为消瘦（低体重与身高比），影响了 3300 万 5 岁以下儿童，但目前尚无针对其治疗的全球指南。我们最近在孟加拉国 12-18 个月大患有 MAM 的儿童中进行了一项针对微生物群导向的补充食品配方（MDCF-2）的随机对照临床试验。结果表明，MDCF-2 每天新鲜制备，对体重增长的改善明显大于标准的即食补充食品（RUSF），这种效果与 MAM 儿童肠道微生物群落发育中断的修复有关。为了在其他地点的急性营养不良儿童中验证这些结果的普遍性，迫切需要一种包装、货架稳定、感官可接受的配方，其生物等效于 MDCF-2。本报告介绍了一项临床研究的方案，该研究旨在评估旨在满足这些标准的候选配方。
在患有 MAM 的 8-12 个月大的孟加拉国儿童中进行一项随机单盲研究，以比较替代的货架稳定 MDCF 原型与每天新鲜制备的当前 MDCF-2 配方的疗效。在治疗前、治疗期间和治疗后，从每个组中纳入的每个儿童的粪便 DNA 样本中生成 V4-16S rDNA 扩增子和 shotgun 测序数据集，以确定 MDCF-2 反应性细菌类群的丰度。通过比较新鲜制备的 MDCF-2 治疗 4 周后 MDCF-2 反应性肠道细菌类群的代表性变化与原型 MDCFs 治疗后其丰度的变化来评估疗效。等效性将定义为在接受测试 MDCF 的参与者中，与 MDCF-2 反应相关的粪便细菌类群的代表性在治疗 4 周后没有统计学上的显著差异。
本试验旨在确定可扩展的、货架稳定的 MDCF-2 配方在 8-12 个月大患有中重度急性营养不良的孟加拉国儿童中的可接受性和等效性，以及对微生物修复的影响。
ClinicalTrials.gov（NCT05094024）。该试验于 2021 年 10 月 23 日开始入组前已注册。
