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

Summary

Background (brief):

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.

Hypothesis to be tested:

In a hypothesis testing research proposal, briefly mention the hypothesis to be tested and provide the scientific basis of the hypothesis, critically examining the observations leading to the formulation of the hypothesis.

Complementary foods made of locally available food ingredients that stimulate the proliferation of growth promoting gut microbiota (MDCF) will provide a new way to improve clinical outcomes, for example by improving growth of children with MAM.

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 ponderal and linear growth in children (iv) improving the metabolomic profile with MAM

Conditions

• Microbiota
• Complementary Food
• Nutrition

Interventions

DIETARY_SUPPLEMENT

Microbiota Directed Complementary Food (MDCF)

MDCF2 with four complementary food ingredients (rationale: lead with evidence from Pre-POC clinical trials to optimize lead microbiota-directed complementary food prototypes for their ability to repair microbiota immaturity and positive effects on growth)

DIETARY_SUPPLEMENT

Ready to Use Supplementary Food (RUSF)

Rice-lentil based RUSF (rationale: reference standard of care for MAM; based on knowledge of its effects on the gut microbiota or microbiota immaturity)

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 · Scientist, Nutrition and Clinical Services Division, icddr,b

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

• Sayeeda Haque, MPH, MBBS · Associate Scientist, Consultant Physician, Nutrition Ward, Nutrition & Clinical Services Division, icddr,b

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

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

• Nurun Nahar Naila, MPH, MBBS · Assistant 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

2021-06-28

Completion

2021-06-28

Countries

• Bangladesh

Study Locations