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

Not Applicable

Recruiting

• Conditions: Malnutrition, Child
• Interventions: Dietary Supplement: RUTF; Dietary Supplement: MDF; Dietary Supplement: RUSF

• Registration Number: NCT06382857
• Lead Sponsor: Epicentre

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-16
• Study First Submitted QC: 2024-04-18
• Study First Posted: 2024-04-24
• Study Start: 2024-05-02
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-26
• Last Update Posted: 2024-08-27
• Primary Completion: 2025-11-01
• Study Completion: 2026-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 7356

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard nutritional treatment (RUTF/RUSF)	RUTF	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.
Standard nutritional treatment (RUTF/RUSF)	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.
Microbiome directed food (MDF)	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Epicentre Niger; 🇳🇪 Maradi, Niger