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)

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

Conditions

• Microbiota
• Complementary Food
• Nutrition

Interventions

DIETARY_SUPPLEMENT

Microbiota Directed Complementary Food-2

MDCF prototype with four complimentary food ingredients without powdered milk (rationale: lead with evidence from the recently completed pre-POC clinical trial of promoting growth promoting microbiota and positive effects on growth

DIETARY_SUPPLEMENT

Ready to Use Supplementary Food

Rice-lentil based RUSF (rationale: reference standard of care for post-SAM, MAM; based on knowledge of its effects on child growth and the gut microbiota)

Sponsors & Collaborators

• Washington University School of Medicine

  collaborator OTHER

• International Centre for Diarrhoeal Disease Research, Bangladesh

  lead OTHER

Principal Investigators

• Tahmeed Ahmed, PhD, MBBS · Senior Director, Nutrition & Clinical Services Division, icddr,b

• Munirul Islam, PhD, MBBS · Senior Scientist, Nutrition and Clinical Services Division, icddr,b

• Sayeeda Haque, MPH, MBBS · Associate scientist, Nutrition and Clinical Services Division, icddr,b

• Ishita Mostafa, MPH, MBBS · Research Investigator, Nutrition and Clinical Services Division, icddr,b

• Imteaz Mahmud, MBBS · Research Fellow, Nutrition and Clinical Services Division, icddr,b

• Nurun Nahar Naila, MPH, MBBS · Assistant Scientist, Nutrition and Clinical Services Division, icddr,b

• Mustafa Mahfuz, MPH, MBBS · Associate scientist, Nutrition & Clinical Services Division, icddr,b

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

12 Months

Max Age

18 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-11-01

Primary Completion

2021-06-30

Completion

2021-06-30

Countries

• Bangladesh

Study Locations