Shelf-Stable MDCF-2 for Children With Undernutrition

Summary

Background: Children with acute malnutrition have immature gut microbial communities compared to age-matched children with healthy growth that can not be repaired by existing therapeutic foods (Subramanian et al., Nature. 2014). Hence, investigators' recent work in Bangladesh has focused on developing Microbiota-Directed Complementary Foods (MDCF) containing locally-available food ingredients, that repair the gut microbiota of children with acute malnutrition to a configuration that resembles that of healthy children living in the same urban community (Raman et al., Science 2019; Gherig et al., Science 2019).

The investigators recently completed a randomized, controlled proof-of-concept (POC) study of current lead microbiota-directed complementary food, MDCF-2 compared to a standard ready-to-use supplementary food (RUSF), in Bangladeshi children with moderate acute malnutrition (MAM)(Chen et al., N Engl J Med 2021). Children who received MDCF-2 for 3 months exhibited significantly greater repair of their gut microbial communities and faster rates of ponderal growth compared to those treated with RUSF (a formulation that was not designed based on knowledge of its effects on the gut microbiota). The superior effect of MDCF-2 on gut microbiota repair and weight gain was even more notable as the RUSF was significantly more energy dense than MDCF-2.

In the aforementioned POC study, MDCF-2 was prepared fresh daily in icddr,b field kitchens prior to distribution and supervised administration to study participants. The lack of a shelf-stable, bio-equivalent formulation of MDCF-2 limits the ability to perform larger studies in Bangladesh as well as in other geographic settings. This pre-POC study in Bangladeshi children with MAM will assess the bioequivalence of MDCF prototypes that the investigators have developed with the potential for improved storage stability compared to current MDCF-2, using the degree of microbiota repair after 4-weeks of treatment as the primary outcome.

Objective: To develop a scalable, shelf-stable formulation that is bioequivalent to MDCF-2 with respect to microbiota repair in 8-12 month-old Bangladeshi children with MAM after 4-weeks of treatment.

Methods: A 5-arm, randomized single-blind pre-POC study will be conducted in 8-12-month-old Bangladeshi children with MAM to compare the efficacy of alternative MDCF formulations in repairing their gut microbiomes compared to the repair produced by the current kitchen prepared MDCF-2 formulation.

Arm 1 - Reference control: kitchen-prepared MDCF-2

Arm 2 - Ready-to-use supplementary food

Arm 3 - Individually packaged, pre-measured sachets of MDCF-2 ingredients, combined and reconstituted in the home setting prior to consumption.

Arm 4 - MDCF-2 shelf-stable foil pouch formulation with green banana powder.

Arm 5 - MDCF shelf-stable foil pouch formulation with sweet potato instead of green banana.

Conditions

• Undernutrition

Interventions

DIETARY_SUPPLEMENT

Central kitchen-prepared version of MDCF-2

Kitchen-prepared MDCF-2 containing chickpea flour, peanut flour, soybean flour, green banana pulp, sugar, soybean oil and micronutrient mix. This version of MDCF-2 will be freshly prepared in central kitchens on a daily basis and provided to participants on the same day. Every child in this arm will be offered 25g of the MDCF-2 formulation twice daily.

DIETARY_SUPPLEMENT

MDCF-2 shelf-stable foil pouch prototype with green banana powder

This shelf-stable foil pouch prototype of MDCF-2 contains chickpea flour, peanut flour, soybean flour, green banana powder, sugar, soybean oil and micronutrient mix, prepared by an industry partner following the formulation developed at icddr,b. Every child in this arm will be offered 21.77g of the formulation twice daily.

DIETARY_SUPPLEMENT

MDCF-2 shelf-stable foil pouch prototype with sweet potato

This shelf-stable MDCF prototype contains chickpea flour, peanut flour, soybean flour, sweet potato, sugar, soybean oil and micronutrient mix. This version of MDCF-2 will be prepared by an industry partner following the formulation developed at icddr,b. Every child in this arm will be offered 23.34g of the MDCF formulation twice daily.

DIETARY_SUPPLEMENT

Freshly reconstituted MDCF-2 ingredients

This version of MDCF-2 is comprised of its individually packaged ingredients. Separate premeasured sachets of chickpea flour, peanut paste, soybean flour, green banana powder, sugar, soybean oil and micronutrient mix will be combined and reconstituted prior to each feeding session. Every child in this arm will be offered 21.72g of the formulation twice daily.

DIETARY_SUPPLEMENT

Ready-to-use supplementary food (RUSF) arm

Locally-produced ready-to-use supplementary food (RUSF) is used as part of a nutritional program to treat moderate acute malnutrition in children over 6 months-of-age. RUSF is eaten directly from the package with no dilution, mixing or cooking. RUSF contains rice, lentil, powdered low-fat milk, soybean flour, sugar, and micronutrient mix. Every child in this arm will be offered 25g of the formulation twice daily.

Sponsors & Collaborators

• Washington University School of Medicine

  collaborator OTHER

• International Centre for Diarrhoeal Disease Research, Bangladesh

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

8 Months

Max Age

12 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-10-31

Primary Completion

2024-08-31

Completion

2025-02-28

Countries

• Bangladesh

Study Locations