Effectiveness of a Microbiome-directed Food to Promote Programmatic and Sustained Nutritional Recovery Among Children With Uncomplicated Acute Malnutrition

This study is an individually randomized controlled trial comparing microbiome-directed foods to standard nutritional therapy among children aged 6 to < 24 months with uncomplicated acute malnutrition in terms of programmatic recovery by 12 weeks from admission and sustained recovery at 24 weeks from admission.

Study Overview

• Status: Recruiting
• Conditions: Malnutrition, Child
• Intervention / Treatment: Dietary supplement: MDF; Dietary supplement: RUTF; Dietary supplement: RUSF

• Study Type: Interventional
• Enrollment (Estimated): 7356
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sheila Isanaka, ScD; Email: sisanaka@hsph.harvard.edu

Study Locations

• Niger
  • Maradi, Niger
    • Recruiting
    • Epicentre Niger
    • Contact: Ousmane Guindo, MD; Email: ousmane.guindo@epicentre.msf.org
    • Contact: Ibrahim Ngoumboute, MD; Email: ibrahim.ngoumboute@epicentre.msf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• for children with Severe Acute Malnutrition (SAM): MUAC < 115 mm and/or WLZ < -3 and/or mild (+) or moderate (++) edema
• for children with Moderate Acute Malnutrition (MAM): 115 mm ≤ MUAC < 125 mm and/or -3 ≤ WHZ < -2
• Caregiver providing informed consent

Exclusion Criteria:

• Medical complications requiring inpatient treatment, as identified by the national protocol
• Not eating/lack of appetite (as informed by appetite test and investigator judgement)
• Re-admission into the program within 2 months of previous default
• for children with Severe Acute Malnutrition (SAM): Referral from inpatient care (therapeutic feeding center, TFC) or supplementary feeding program (SFP)
• for children with Moderate Acute Malnutrition (MAM): Referral from SAM treatment (TFC or OTP)
• Presence of congenital abnormality or underlying chronic disease that may affect growth or risk of infection
• Known contraindication/ hypersensitivity/allergy to study interventions (chickpea/soy flour, banana, peanut)
• Residence outside the study catchment area or in a non-fixed (e.g. nomadic) community

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Microbiome directed food (MDF); The MDF in this study was developed by the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,B). This MDF is the lead icddr,B prototype that has demonstrated the strongest increase in biomarkers critical to growth, including growth hormone receptor and leptin, and re-establishment of the maturity of the microbiome among moderately malnourished children. Ingredients include chickpea flour, soy flour, peanut paste, green banana powder, sugar, oil, and micronutrients. The same MDF is provided for the treatment of SAM and MAM at modified doses.	Dietary supplement: MDF; MDF will be provided to children on a weekly basis for children with SAM and bi-weekly basis for children with MAM at the health center until programmatic recovery but not thereafter.
Active Comparator: Standard nutritional treatment (RUTF/RUSF); The standard RUTF used in this study for the treatment of SAM is Plumpy'Nut (Nutriset France). RUTF is a specialized therapeutic food that can be consumed without preparation and meets the nutritional requirements for the recovery of SAM. Ingredients include oil, peanut, skimmed milk powder, sugar and micronutrients. The standard RUSF used in this study is Plumpy'Sup (Nutriset France). RUSF is a lipid-based nutritional supplement with a high vitamin and mineral content, specifically designed for the treatment of MAM. Ingredients include oil, peanut, skimmed milk powder, sugar and micronutrients.	Dietary supplement: RUTF; RUTF will be provided to all children on a weekly basis at the health center until programmatic recovery but not thereafter; Other Names: Standard RUTF; Dietary supplement: RUSF; RUSF will be provided on a biweekly basis at the health center until programmatic recovery but not thereafter; Other Names: Standard RUSF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Programmatic recovery by 12 weeks from admission	Defined as the proportion of SAM and MAM children achieving a WLZ ≥ -2 AND MUAC ≥ 125mm AND no edema during 2 consecutive visits	12 weeks
Sustained recovery at 24 weeks from admission	Proportion of recovered SAM and MAM children with WLZ ≥ -2 AND MUAC ≥ 125mm AND no edema	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Default	Defined as 2 consecutive missed scheduled program visits	12 weeks
Non-response	Defined as WLZ < -2 or MUAC < 125 mm during 2 consecutive visits, or for SAM children only: persistent edema at 12 weeks	12 weeks
Time to recovery	Measured as days from admission to programmatic recovery among recovered children	12 weeks
For MAM children: Deterioration to SAM	Weight-for-height z-score (WHZ) inferior to -3	24 weeks
Change in weight gain	Change in g/kg/day	From enrollment to 4, 8 and 12 weeks
Change in MUAC	Change in mm	From enrollment to 4, 8 and 12 weeks
Serious adverse events	Combined safety endpoint, including hospitalization and death	24 weeks
Hospitalization	Inpatient stay > 24h	24 weeks
Death	All-cause mortality	24 weeks
Motor, cognitive, language, social-emotional, and mental health skills	As measured by the Caregiver Reported Early Development Instrument (CREDI)	24 weeks
Cost effectiveness	As defined by the incremental cost per child recovered and per child sustained recovered	24 weeks
Dietary intake	As measured by 24h recall	24 weeks
Adherence	Defined as the sum of sachets returned used divided by the total number of sachets distributed	12 weeks
Microbiome profile at enrollment, week 4, program discharge, and study discharge	Defined as PCR-confirmed enteric viral, bacterial, and protozoan pathogens present	24 weeks
Plasma proteome profile at enrollment, week 4, program discharge, and study discharge	Defined as circulating plasma proteins (IGFBP-2, thrombospondin-5, granulysin, GDF-15, and MMP-8)	24 weeks
Environmental enteric dysfunction at enrollment, program discharge, and study discharge	Measured by anti-LPS IgA and IgG; anti-flagellin IgA and IgG; sCD14; I-FABP; myeloperoxidase (MPO); and calprotectin	24 weeks
Change of fat mass and fat-free mass at program discharge and study discharge	Measured by deuterium dilution	24 weeks
Micronutrient status at enrollment, program discharge and study discharge	Defined as ferritin; soluble transferrin binding protein; alpha-tocopherol; retinol; folate; and vitamin B12	24 weeks
Immuno-sufficiency at week 2, week 4, program discharge, week 12 and study discharge (SAM only)	As defined by T-cell receptor excision circles (TRECs) and kappa-receptor excision circles (KRECs)	24 weeks
Change in weight-for-length Z (WLZ)	Change in WLZ calculated using the 2006 WHO Growth Standards	From enrollment to 4, 8 and 12 weeks
Change in length-for-age Z (LAZ)	Change in LAZ calculated using the 2006 WHO Growth Standards	From enrollment to 4, 8 and 12 weeks
Change in weight-for-age Z (WAZ)	Change in WAZ calculated using the 2006 WHO Growth Standards	From enrollment to 4, 8 and 12 weeks

Collaborators and Investigators

• Sponsor: Epicentre
• Collaborators: Epicentre, Niger; National Nutrition Direction, Niger; Ministry of Public Health and Social Affairs, Niger; Regional Direction of Public Health, Maradi
• Investigators: Study Chair: Rebecca Grais, PhD, Epicentre

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 18, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 26, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Child; Microbiome; Malnutrition; SAM; MAM; MDF
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Child Nutrition Disorders
• Other Study ID Numbers: 823779-MDF Niger

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No