Community-based Clinical Trial With Microbiota-directed Complementary Foods (MDCFs) Made of Locally Available Food Ingredients for the Management of Children With Primary Moderate Acute Malnutrition

Primary Investigator

  • Tahmeed Ahmed

Study Period

November 2018 - June 2021

Study Description

Burden: A total of 52 million children under 5 are suffering from acute malnutrition globally, of whom 33 million have moderate acute malnutrition (MAM). In Bangladesh, more than 2 million children suffer from MAM. According to Bangladesh Demographic Health Survey 2014 26%, 25% and 17% of children aged less than two years are stunted, underweight and wasted respectively.

Knowledge gap: It has been already demonstrated that children with SAM have immature gut microbiota that is partially corrected with treatment. Children with MAM have an increased risk of mortality, infections and impaired physical and cognitive development compared to well-nourished children. Although the global caseload of MAM is much greater than that of SAM, the condition has not received the same level of attention or priority. Through our previous and ongoing research we now know about the members of the gut microbiota that can promote growth in children and also about certain food ingredients that promote the proliferation of such beneficial microbiota. However, this knowledge needs to be applied on a sufficiently powered community-based clinical trial.

Relevance: The rationale for this study is to assess whether long-term administration of complementary food made of locally available food ingredients can stimulate the proliferation of growth promoting members of the gut microbiota and have a positive impact on child growth. Such a food (the microbiota directed complementary food; MDCF-2) has been identified through our recently concluded Pre-proof of concept trial done on children with primary MAM. We would now like to do a clinical community-based trial of this potential MDCF-2 in the management of children with primary MAM.

Hypothesis: Complementary foods made of locally available food ingredients that stimulate the proliferation of growth promoting gut microbiota (MDCF-2) will improve clinical outcomes.

Methods: We will conduct a proof of concept (POC) clinical trial in 12-18 months old children with primary MAM (Weight-for-Length Z-score, WLZ between -2 and -3). This study will be conducted at Bauniabadh, Radda MCH-FP (Maternal and Child Health- Family Planning) clinic, Gabtoli of Mirpur area and possibly at the Special Nutrition Unit run by Terre des Hommes in Kurigram. We will produce MDCF-2 at the icddr,b Food Processing Laboratory or nutrition centre established at the site in sufficient quantities for clinical study. This formulation will be matched in energy density and micronutrient content of ready-to-use supplementary foods (RUSFs) used for MAM in Bangladesh and other countries, and will meet all other requirements for a complementary/supplementary food for 12-18 months old children with MAM. We will test MDCF-2 and the current RUSF standard of care for primary MAM to see the effect on growth, proteomics and metabolomics of an intervention for 12 weeks, with a 4-week post-intervention phase.

Study Arms

  • Experimental (Intervention Arm): Dietary Supplement: Microbiota Directed Complementary Food (MDCF): MDCF2 with four complementary food ingredients
  • Active Comparator (Control Arm): Dietary Supplement: Ready to Use Supplementary Food (RUSF): Rice-lentil based RUSF

Primary Outcomes

  • Change in Ponderal growth [ Time Frame: At the enrollment (day1), every 15 days during the 3 months of intervention phase and at the end of 1 month of follow up phase by anthropometry ] Rate of weight gain of the enrolled participants
  • Change in Linear growth (LAZ), [ Time Frame: At the enrollment (day1), every 15 days during the 3 months of intervention phase and at the end of q month of follow up phase by anthropometry ] Rate of skeletal human growth
  • Change in Proteomic profile [ Time Frame: A total of 3 Plasma samples will be collected, just before the start of intervention phase, at the end of first month of intervention phase and just after the completion of 3rd month. ]
  • Change in Morbidity [ Time Frame: Data will be collected every day during the 3 months of intervention phase and once at the end of 1 month of follow up phase. ] Assessed by morbidity data.
  • Change in microbiota-for-age Z score [ Time Frame: At the enrollment, at the beginning of the intervention phase, weekly during the 1st month of intervention, at the end of 2nd and 3rd months of intervention and at the end of 1 month of follow up phase. ]

Study Interventions

  • Environmental enteric dysfunction (EED)
  • Fortified blended foods (FBF)

Research Gaps

  • Effectiveness

    How well do different food compositions and interventions prevent or treat undernutrition, when implemented "on the ground"?

  • Innovation

    What novel food-based products and programming methods effectively prevent and treat undernutrition?

Study Population