Microbiome-Directed Food for Sustained Recovery From Acute Malnutrition

Study Overview
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Brief Summary
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The goal of this experimental study is to test the efficacy of a new formulation - The microbiome-directed food (MDF) to treat acute malnutrition among children aged 6 to 23 months. The main questions it aims to answer are: Does treating children with moderate or severe uncomplicated malnutrition using MDF leads to higher programmatic recovery rate compared to standard of care ? Does treating children with moderate or severe uncomplicated malnutrition using MDF leads to higher sustained recovery rate compared to standard of care ? The MDF will be compared to Ready-to-use supplementary food (RUSF) and a locally available food (LAF) for moderately malnourished children, and to Ready-to-use therapeutic food (RUTF) for severely malnourished children to see the effects on recovery and sustained recovery rate.

Detailed Description
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In this stratified trial, children presenting at the health center and fulfilling the inclusion criteria will randomly assigned to study groups. The supplementation will be done on daily basis according to the child's weight for a maximum of 12 weeks, at which point the recovery assessment is done. Each child will be subsequently followed up to 24 weeks for recovery assessment. Follow-up visits will be done at the health center every week for severe acute malnutrition (SAM) children and every two weeks for moderate acute malnutrition (SAM) children

Official Title
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Efficacy of a Food Targeting the Microbiota for a Sustained Recovery of Children With Uncomplicated Acute Malnutrition

Conditions
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Acute Malnutrition in Childhood

Intervention / Treatment
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* Dietary Supplement: Microbiome-directed food - MAM
* Dietary Supplement: Ready-to-use supplementary food (RUSF)
* Dietary Supplement: Locally available food
* Dietary Supplement: Microbiome-directed food (MDF) - SAM
* Dietary Supplement: Ready-to-use therapeutic food (RUTF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 6 and 23 months Moderate wasting: WHZ < -2 and ≥ -3 or MUAC < 125 mm and ≥ 115mm or - Severe wasting: WHZ < -3 or MUAC < 115 mm Exclusion Criteria: Bilateral pitting edema Not eating/lack of appetite Current illness medical complications requiring inpatient treatment Presence of any congenital abnormality or underlying chronic disease that may affect growth or risk of infection Known contraindication/hypersensitivity/allergy to MDCF of RUSF ingredients (chickpea flour, soy flour, banana, peanut) Relapse from MAM treatment or transfer from SAM treatment Children recently (<2 months) or enrolled in a nutrition program Residence outside the study area

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 23 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Individually randomized and controlled trial, Stratified by severity of malnutrition: 2 arms for Severe Acute malnutrition 3 arms for Moderate acute Malnutrition
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Microbiome-directed food (MDF) - MAM<br>Each (MAM) child will receive a daily ration of MDF corresponding to his weight, for maximum 12 weeks of supplementation | Dietary Supplement: Microbiome-directed food - MAM<br>* Each MAM child will be supplemented with MDF for a maximum of 12 weeks. He will be followed subsequently up to 24 weeks.<br>* Other names: MDF - MAM;|
| Active Comparator: Ready-to-use supplementary food (RUSF)<br>Each (MAM) child will receive a daily ration of MDF corresponding to his weight, for maximum 12 weeks of supplementation | Dietary Supplement: Ready-to-use supplementary food (RUSF)<br>* Each MAM child will be supplemented with RUSF for a maximum of 12 weeks. He will be followed subsequently up to 24 weeks.<br>* Other names: RUSF;|
| Active Comparator: Locally available Food<br>Each (MAM) child will receive a basket of food ingredients to prepare a complementary food at home. The quantity of ingredients is based on child's weight. The food is given a maximum duration of 12 weeks. | Dietary Supplement: Locally available food<br>* Each MAM child will consume a food made of locally available ingredients for a maximum of 12 weeks. He will be followed subsequently up to 24 weeks.<br>* Other names: LAF;|
| Experimental: Microbiome-directed food (MDF) - SAM<br>Each (SAM) child will receive a daily ration of MDF corresponding to his weight, for maximum 12 weeks of supplementation. | Dietary Supplement: Microbiome-directed food (MDF) - SAM<br>* Each SAM child will be supplemented with MDF for a maximum of 12 weeks. He will be followed subsequently up to 24 weeks.<br>* Other names: MDF - SAM;|
| Active Comparator: Ready-to-use therapeutic food (RUTF)<br>Each (SAM) child will receive a daily ration of RUTF corresponding to his weight, for maximum 12 weeks of supplementation | Dietary Supplement: Ready-to-use therapeutic food (RUTF)<br>* Each SAM child will be supplemented with RUTF for a maximum of 12 weeks. He will be followed subsequently up to 24 weeks.<br>* Other names: RUTF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Programmatic recovery defined by Weight-for-height (WHZ) ≥ - 2 z-score or mid-upper arm circumference (MUAC) ≥ 125 mm | Moderate cute malnutrition is defined by Weight-for-height (WHZ) < - 2 z-score or mid-upper arm circumference (MUAC) < 125 mm. Higher WHZ z-score (≥ - 2) or mid-upper arm circumference (MUAC) ≥ 125 mm means better outcome synonym of recovery | 12th weeks from admission to the supplementation program | 
| Sustained recovery defined by WHZ ≥ - 2 z-score or MUAC ≥ 125 mm | Children who sustain recovery (WHZ ≥ - 2 z-score or MUAC ≥ 125 mm) up to 24 weeks | 24 weeks from admission to the supplementation program | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in Weight-for-height (WHZ) z-score | (WHZ z-score at admission) - (WHZ z-score at 12 weeks) | 12 weeks from admission to the supplementation program | 
| Mean change in Weight-for-age (WAZ) z-score | (WAZ z-score at admission) - (WAZ z-score at 12 weeks) | 12 weeks from admission to the supplementation program | 
| Mean change in Height-for-age (HAZ) z-score | (HAZ z-score at admission) - (HAZ z-score at 12 weeks) | 12 weeks from admission to the supplementation program | 
| Time to recovery | Determined by the number of days from admission to programmatic recovery among those who recovered | Up to 12 weeks | 
| Dropouts | Lost to follow up | 12 weeks | 
| Non-response defined by WHZ < -2 z-score, or a MUAC < 125 mm | Children who failed to attain a weight-for-height (WHZ) ≥ - 2 z-score or mid-upper arm circumference (MUAC) ≥ 125 mm | 12 weeks | 
| Complications | Edema Fever >39°C or hypothermia <35°C Severe dehydration Repeated or incessant vomiting Severe respiratory problem (IMCI criteria) severe anemia (significant pallor with difficulty of breathing) Severe malaria Abscess or extensive skin lesions Very weak, apathetic, unconscious Seizure | up to 12 weeks | 
| Failure | Absence of weight gain, assessed at the 3rd consecutive visit; Weight loss since admission to the program, assessed at the 1st visit after admission; Loss of 5% of body weight compared to admission weight. | up to 12 weeks |