Community-based Clinical Trial With Microbiota Directed Complementary Foods (MDCFs) Made of Locally Available Food Ingredients for the Management of Children With Post-severe Acute Malnutrition Moderate Acute Malnutrition (Post-SAM MAM)

Primary Investigator

  • Tahmeed Ahmed

Study Period

November 2018 - February 2021

Study Description

Brief Summary:

Background (brief):

  1. Burden: A total of 52 million children under 5 are suffering from acute malnutrition globally, of whom 33 million suffer from moderate acute malnutrition (MAM). In Bangladesh, around 2 million children suffer from MAM. In absolute numbers, according to Bangladesh Demographic Health Survey 2014, 26%, 25% and 17% of children aged less than two years are stunted, underweight and wasted respectively.1
  2. Knowledge gap: We have already demonstrated that children with acute malnutrition 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 large scale community-based clinical trial.
  3. Relevance: The rationale for this study is to assess whether long-term administration of complementary food made of locally available food ingredients that can stimulate the proliferation of growth promoting gut microbiota (MDCF-2), as identified in our Pre-POC trial, is able to produce predictable changes in the microbiota of Bangladeshi children with Post-SAM MAM as well as in their nutritional status. We would now like to do a community-based clinical trial of this potential MDCF-2 in the management of children with Post-SAM MAM.

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

Objectives: To investigate the efficacy of complementary food made of locally available food ingredients that can stimulate the proliferation of growth promoting gut microbiota (Microbiota Directed Complementary Food: MDCF-2) in (i) promoting repair of microbiota immaturity (ii) promoting proliferation of beneficial bacteria (iii) improving both linear and ponderal growth in children with Post-SAM MAM (iv) improving the metabolomic profile of children with Post-SAM MAM

Methods: We will conduct a proof of concept (POC) clinical trial in 12-18 months old children with post-SAM MAM (Weight-for-Length Z-score, WLZ <-2 to -3) over the course of approximately two years. This study will be undertaken at Mirpur area of Dhaka city and in Kurigram. We will produce MDCF-2 at the icddr,b Food Processing Laboratory in sufficient quantities for the trial. This formulation is matched for energy density and micronutrient content of ready to use supplementary food (RUSF) used for MAM. It itself is not a ready-to-use food but is rather a cooked food made of locally available food ingredients (chickpea, green banana, peanut, soybean flour) which have been found to enhance growth promoting members of the gut microbiota in children. We will test MDCF-2 and the current RUSF standard of care for Post SAM MAM to see the effect on growth, proteomics and metabolomics of an intervention for 12 weeks, with a 4-week post-intervention phase.

Outcome measures/variables:

  • Ponderal growth (rate of weight gain as the primary outcome variable), measured at different time points by anthropometry
  • Linear growth, measured at different time points by anthropometry
  • Proteomic profile, assayed by DNA aptamer based SOMAlogic scan
  • Morbidity, assessed by daily records
  • Change in microbiota-for-age Z score

Hypothesis to be tested:

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

Specific Objectives To investigate the efficacy of complementary food made of locally available food ingredients that can stimulate the proliferation of growth promoting gut microbiota (Microbiota Directed Complementary Food: MDCF-2) in

(i) promoting repair of microbiota immaturity (ii) promoting proliferation of beneficial bacteria (iii) improving both linear and ponderal growth in children with Post-SAM MAM (iv) improving the metabolomic profile of children with Post-SAM MAM

Study Arms

  • Experimental: Intervention arm MDCF-2 prototype with four complimentary food ingredients without powdered milk
  • Active Comparator: Control arm Rice-lentil based RUSF

Primary Outcomes

  • Change in Ponderal growth
  • Change in Liner growth (LAZ)
  • Change in Proteomic profile
  • Change in Morbidity
  • Change in Microbiota-for-Age Z (MAZ) score

Study Interventions

  • Environmental enteric dysfunction (EED)
  • Standard Fortified Food Blends
  • Locally produced

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

124