Shelf-Stable MDCF-2 for Children With Undernutrition

NCT05094024 | Unknown

• 1 other identifier: PR-21019
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Equivalence in the response to MDCF-2 and a test MDCF formulation, based on the change in representation of gut bacterial taxa after 4-weeks of treatment with MDCF-2, compared to the change after treatment with the test MDCF for 4-weeks.

  V4-16S rDNA amplicons and shotgun sequencing datasets will be generated from fecal samples collected from each child in each group prior to, during, and after treatment to determine the abundances of MDCF-2 responsive bacterial taxa. Equivalence will be defined as the absence of a statistically significant difference after 4-weeks of treatment in the representation of fecal bacterial taxa associated with the response to MDCF-2 in participants receiving a test MDCF, compared to the representation of these bacterial taxa in participants after receiving the reference MDCF-2 formulation for 4-weeks.

  Baseline to 4-weeks of treatment.

Other Outcomes (2)

• Changes in the abundances of 7000 circulating plasma proteins

  Baseline to end of Week 4

• Changes in the concentrations of fecal protein biomarkers of gut inflammation

  Baseline to end of Week 4

Study Arms (5)

Central kitchen-prepared MDCF-2 arm

ACTIVE COMPARATOR

Children randomized to this arm will receive 25gm of kitchen-prepared version of MDCF-2 twice daily.

Dietary Supplement: Central kitchen-prepared version of MDCF-2

Ready-to-use supplementary food (RUSF) arm

EXPERIMENTAL

Children randomized to this arm will receive 25g RUSF twice daily.

Dietary Supplement: Ready-to-use supplementary food (RUSF) arm

Freshly reconstituted MDCF-2 ingredients

EXPERIMENTAL

Children randomized to this arm will receive individually packaged MDCF-2 ingredients, combined into 21.72g servings provided twice daily.

Dietary Supplement: Freshly reconstituted MDCF-2 ingredients

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

EXPERIMENTAL

Children randomized to this arm will receive 21.77gm of shelf-stable foil pouch prototype with green banana powder twice daily.

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

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

EXPERIMENTAL

Children randomized to this arm will receive 23.34gm of MDCF prototype with sweet potato twice daily.

Dietary Supplement: MDCF-2 shelf-stable foil pouch prototype with sweet potato

Interventions

Central kitchen-prepared version of MDCF-2 DIETARY_SUPPLEMENT

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.

Central kitchen-prepared MDCF-2 arm

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

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.

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

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

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.

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

Freshly reconstituted MDCF-2 ingredients DIETARY_SUPPLEMENT

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.

Freshly reconstituted MDCF-2 ingredients

Ready-to-use supplementary food (RUSF) arm DIETARY_SUPPLEMENT

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.

Ready-to-use supplementary food (RUSF) arm

Eligibility Criteria

• Age: 8 Months - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Parent(s) willing to sign consent form
• Child aged 8-12 months
• WLZ score \<-2 to -3 without bilateral pedal edema at the time of randomization
• Parent(s) willing to bring the child to the feeding centre according to the pre-defined schedule

You may not qualify if:

• Medical conditions: Malnourished children with complications requiring acute phase treatment in a hospital, children with tuberculosis (diagnosis based on WHO 2014 guidelines which have been incorporated in the national TB control guidelines of Bangladesh). The guidelines depend upon the following five diagnostic principles (three out of five should be positive):
• Specific symptoms of TB
• Specific signs of TB
• Chest X-ray
• Mantoux test
• History of contact
• Severe anemia (\< 8 mg/dl)
• Antibiotic use (within last 15 days before the onset of intervention)
• Ongoing maternal antibiotic usage for breastfeeding infants
• Receiving concurrent treatment for another condition

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Mirpur

Dhaka, 1221, Bangladesh

RECRUITING

Related Publications (6)

• Raman AS, Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, Subramanian S, Kang G, Bessong PO, Lima AAM, Kosek MN, Petri WA Jr, Rodionov DA, Arzamasov AA, Leyn SA, Osterman AL, Huq S, Mostafa I, Islam M, Mahfuz M, Haque R, Ahmed T, Barratt MJ, Gordon JI. A sparse covarying unit that describes healthy and impaired human gut microbiota development. Science. 2019 Jul 12;365(6449):eaau4735. doi: 10.1126/science.aau4735.

  PMID: 31296739 RESULT

• Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, Kung VL, Cheng J, Chen RY, Subramanian S, Cowardin CA, Meier MF, O'Donnell D, Talcott M, Spears LD, Semenkovich CF, Henrissat B, Giannone RJ, Hettich RL, Ilkayeva O, Muehlbauer M, Newgard CB, Sawyer C, Head RD, Rodionov DA, Arzamasov AA, Leyn SA, Osterman AL, Hossain MI, Islam M, Choudhury N, Sarker SA, Huq S, Mahmud I, Mostafa I, Mahfuz M, Barratt MJ, Ahmed T, Gordon JI. Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Science. 2019 Jul 12;365(6449):eaau4732. doi: 10.1126/science.aau4732.

  PMID: 31296738 RESULT

• Subramanian S, Huq S, Yatsunenko T, Haque R, Mahfuz M, Alam MA, Benezra A, DeStefano J, Meier MF, Muegge BD, Barratt MJ, VanArendonk LG, Zhang Q, Province MA, Petri WA Jr, Ahmed T, Gordon JI. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature. 2014 Jun 19;510(7505):417-21. doi: 10.1038/nature13421. Epub 2014 Jun 4.

  PMID: 24896187 RESULT

• Chen RY, Mostafa I, Hibberd MC, Das S, Mahfuz M, Naila NN, Islam MM, Huq S, Alam MA, Zaman MU, Raman AS, Webber D, Zhou C, Sundaresan V, Ahsan K, Meier MF, Barratt MJ, Ahmed T, Gordon JI. A Microbiota-Directed Food Intervention for Undernourished Children. N Engl J Med. 2021 Apr 22;384(16):1517-1528. doi: 10.1056/NEJMoa2023294. Epub 2021 Apr 7.

  PMID: 33826814 RESULT

• Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016 Jul;13(7):581-3. doi: 10.1038/nmeth.3869. Epub 2016 May 23.

  PMID: 27214047 RESULT

• Mostafa I, Fahim SM, Das S, Gazi MA, Hasan MM, Saqeeb KN, Mahfuz M, Lynn HB, Barratt MJ, Gordon JI, Ahmed T. Developing shelf-stable Microbiota Directed Complementary Food (MDCF) prototypes for malnourished children: study protocol for a randomized, single-blinded, clinical study. BMC Pediatr. 2022 Jul 1;22(1):385. doi: 10.1186/s12887-022-03436-6.

  PMID: 35778675 DERIVED

MeSH Terms

Conditions

Malnutrition

Condition Hierarchy (Ancestors)

Nutrition Disorders; Nutritional and Metabolic Diseases

Central Study Contacts

Tahmeed Ahmed, PhD

CONTACT

01713044799; tahmeed@icddrb.org

Shah Mohammad Fahim, MPH

CONTACT

01912682540; mohammad.fahim@icddrb.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: October 26, 2021
• Study Start: October 31, 2021
• Primary Completion: August 31, 2024
• Study Completion: February 28, 2025
• Last Updated: February 8, 2022

Record last verified: 2022-01

Locations

BA (1)