Microbiota-directed complementary foods to treat children with moderate acute malnutrition in the first two years of life – Open label Randomized controlled Pre-proof of Concept (MDCF prePOC) study
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 630
- 试验地点
- 3
- 主要终点
- 1.Acceptability of the food supplements (MDCF and RUSF) amongst study participants and caregivers and compliance to the intervention.
研究概览
简要总结
Acute malnutrition amongst under five children is a significant public health problem in India and leads to adverse consequences on survival, growth and development. Recently conducted studies have demonstrated impaired gut microbiota development in children with acute malnutrition during the first two years of life with lower microbiota for age Z-score (MAZ) compared to healthy infants. This microbiota immaturity may not be repaired by existing nutritional interventions. Microbiota directed food supplement (MDCF) is a specialised nutritional intervention developed through a series of research studies conducted in Bangladeshi children which has demonstrated potential for repairing the defect in the gut microbial community and is associated with improved growth and development in children aged 12-18 months. We plan to assess the acceptability, generalisability and efficacy of MDCF in Indian children with moderate acute malnutrition (MAM) aged 6-18 months in geographically different locations in India (Delhi, Pune and Vellore). The study will be conducted in 2 phases, i.e. the pre-proof of concept (prePOC) study and the proof of concept (POC) study. In the prePOC study, the primary purpose is to assess acceptability and feasibility of delivering the intervention. In the latter phase, we will evaluate generalisability and efficacy of the intervention.
The present prePOC study is a multi-centric (3-site) study to establish the acceptability and feasibility of the intervention and to establish the systems for sample collection, storage and transport.
Total 80 children with MAM (40 aged 6-<12 months, and 40 aged 12 -18 months) will be enrolled at each site. Each age strata will be randomised in 1:1 ratio to receive MDCF or ready-use supplementary food (RUSF) for a period of 4 weeks. MDCF will be freshly prepared daily in the study sites. The food supplements will be delivered under direct observation by health workers. The study participants will undergo fecal sample collection every week for assessment of the gut microbiome. Blood samples (2-3 ml) will be collected at baseline and at the end of the intervention to assess the plasma proteomic profile. The children will be followed up for 2 weeks after the end of the intervention to assess whether changes in the gut microbial community are sustained post-intervention. The primary outcome parameters will include acceptability and compliance to the intervention, feasibility of the intervention and biological specimen collections. Secondary outcomes are changes in microbiota for age Z scores (MAZ), enterobacterial burden, and change in the plasma proteomic profile. Additionally, a cohort of 130 healthy children aged 3-months at each site will be longitudinally followed up for 24 months and their fecal samples will be collected every month to establish a reference MAZ score in the population for comparing against children with MAM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 90.00 Day(s) 至 18.00 Month(s)（—）
- 性别
- All
入选标准
- •INTERVENTIONAL COHORT: 1.Children aged 6-18 months of either gender and no longer exclusively breastfed 2.Weight to length Z (WLZ) score <−2 to -3 without bilateral pedal edema at the time of randomization (for MAM children) 3.Parent(s) willing for study participation and aid in following study procedures 4.Agree to remain in the study area for the study duration HEALTHY COHORT:
- •Age between 90 days to 119 days (3 to < 4 months)
- •Anthropometric scores (WLZ above -1SD)
- •Willing to stay in the study area for 2 years.
排除标准
- •INTERVENTIONAL COHORT: 1.Any ongoing fever or medical condition persisting for >last 14 days or requires hospitalization 2.Any congenital/acquired disorder affecting growth 3.History of soy, milk protein or peanut allergy 4.Severe pallor on examination 5.Antibiotic use (within last 15 days before the onset of intervention) 6.Ongoing maternal antibiotic usage for breastfeeding infants 7.Receiving concurrent treatment for another condition 8.Failure to obtain informed written consent from parents/guardians 9.Any other condition that in the opinion of the study investigator serves as an exclusion Note: Criteria No 1, 4, 5,7 will be temporary exclusion criterion, children will be eligible for inclusion if they are not having any medical conditions, severe pallor, antibiotic use on any concurrent treatment for last 15 days from the day of enrolment.
- •HEALTHY COHORT:
- •No history of antibiotic consumption in the past 15 days (temporary exclusion)
- •History of any medical illness in the past 15 days (temporary exclusion)
- •Any medical condition persisting for >last 14 days prior to enrolment or requires hospitalization (temporary exclusion)).
结局指标
主要结局
1.Acceptability of the food supplements (MDCF and RUSF) amongst study participants and caregivers and compliance to the intervention.
时间窗: 1. At week 2 to Week 6 from enrollment | 2. during overall study period.
2.Feasibility of collection, transport and storage of fecal samples
时间窗: 1. At week 2 to Week 6 from enrollment | 2. during overall study period.
次要结局
- Microbiota for age Z-score (MAZ).(At week 0 to week 8 except week 7 for the interventional cohort and every month of healthy cohort)
- Enteropathogenic burden (estimated using PCR-based analysis of the fecal samples)(end of study)
- Metabolic markers: Plasma proteomic profile (including mediators of bone growth and ossification, proteins associated with ponderal growth, and CNS development).(At week 2 and week 6 from enrollment)
- Weight-for-length z-score (WLZ), weight-for-age z-score (WAZ), length-for-age z-score (LAZ) and mid-upper arm circumference (MUAC) at the end of the study.(At week 8 from enrollment)