Comparing Several Strategies to Manage Moderate Acute Malnutrition Among Children From 6 to 24 Months Old

Phase 3

Completed

• Conditions: Moderate Acute Malnutrition
• Interventions: Drug: Albendazole; Drug: Azythromycin; Dietary Supplement: Inuline and fructo-oligosaccharides; Dietary Supplement: Fortified blend flour

• Registration Number: NCT03474276
• Lead Sponsor: Institut Pasteur

Brief Summary

The aim of this open-label randomized controlled trial conducted in four African countries (Madagascar, Niger, Central African Republic and Senegal) is to compare three strategies of renutrition for moderate acute malnutrition (MAM) in children based on modulation of the gut microbiota with enriched flours alone, enriched flours with prebiotics or enriched flours coupled with antibiotic treatment. Cognitive development of children (Senegal) will also be studied and compared.

Detailed Description

The main objective of this study is to improve the nutrition strategy used to take in charge moderate acute malnutrition (MAM) which is the major milestone before severe malnutrition. This will be based on the modulation of the gut microbiota with adjunct product added to standard nutrition flours.

The purpose of the MALINEA study is to compare three management strategies for Moderate Acute Malnutrition (MAM) in children aged between 6 months and 2 years old on recovery defined by a weight/size gain at 3 months.

The 3 groups will be compared on several anthropometric measurements \[Weight, length, Mid Upper Arm Circumference (MUAC)\], clinical characteristics, adherence and tolerance to interventions between before and after a 3 months intervention Cognitive development of children (Senegal) will also be studied and compared, at inclusion, 3 months and 6 months after inclusion.

The investigators will also investigate the microbiomes of malnourished children at inclusion and at 3 and 6 months after inclusion to compare it to the ones of normonourished children.

Study Timeline

• Study First Submitted: 2016-06-13
• Study Start: 2018-01-31
• Study First Submitted QC: 2018-03-15
• Study First Posted: 2018-03-22
• Primary Completion: 2018-12-31
• Study Completion: 2019-06-30
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-23
• Last Update Posted: 2022-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1357

Inclusion Criteria

• Children aged from 6 to 24 months olds.
• Moderate acute malnutrition defined by a -3 ≤ Weight/Height z-score < -2 SD.
• Written informed consent of parents or legal guardian.
• Child able to be brought back to the centre on the two following days of inclusion.
• Child able to be followed up during at least three months.

Exclusion Criteria

• Severe malnutrition defined by a mid upper arm circumference < 115 mm OR Weight/Height z-score < -3 SD OR presence of nutritional oedema.
• Clinical complications or according to the physician any clinical sign requiring care outside of the recruitment centre (referral to specialised centre or hospitalisation)
• Diarrhea with mucus and bloody stools.
• Current incompatible treatment : Antacids, Cetirizine, Digoxin, Ergotamine, Azidothymidine.
• Known hypersensitivity to macrolides or albendazole (or one of its components)
• Known allergy to enriched flours or prebiotics used in the study, or one of its components.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Albendazole	Fortified Blended Flour (in association with a single dose of Albendazole at inclusion for children older than 12 months). 200 grams / day for children between 6 and 11 months. 300 grams / day for children aged from 12 to 24 months old.
Control group	Fortified blend flour	Fortified Blended Flour (in association with a single dose of Albendazole at inclusion for children older than 12 months). 200 grams / day for children between 6 and 11 months. 300 grams / day for children aged from 12 to 24 months old.
Azythromycin	Azythromycin	Fortified Blended Flour (in association with a single dose of Albendazole at inclusion for children older than 12 months) associated to Azythromycin, 20mg/kgs/days during the three first days of the study.
Azythromycin	Albendazole	Fortified Blended Flour (in association with a single dose of Albendazole at inclusion for children older than 12 months) associated to Azythromycin, 20mg/kgs/days during the three first days of the study.
Azythromycin	Fortified blend flour	Fortified Blended Flour (in association with a single dose of Albendazole at inclusion for children older than 12 months) associated to Azythromycin, 20mg/kgs/days during the three first days of the study.
Prebiotic	Inuline and fructo-oligosaccharides	Fortified Blended Flour mixed with Inuline and fructo-oligosaccharides (Synergy1) 2g/day, given to the child through the whole intervention (in association with a single dose of Albendazole at inclusion for children older than 12 months)
Prebiotic	Albendazole	Fortified Blended Flour mixed with Inuline and fructo-oligosaccharides (Synergy1) 2g/day, given to the child through the whole intervention (in association with a single dose of Albendazole at inclusion for children older than 12 months)
Prebiotic	Fortified blend flour	Fortified Blended Flour mixed with Inuline and fructo-oligosaccharides (Synergy1) 2g/day, given to the child through the whole intervention (in association with a single dose of Albendazole at inclusion for children older than 12 months)

Primary Outcome Measures

Name	Time	Method
Recovery at three month	Three month	Recovery at three months, defined by: Weight/Size Z-score ≥ -1.5 SD measured at 2 following consultations without hospitalization, transfer, death or lost to follow up

Secondary Outcome Measures

Name	Time	Method
Comparison of the Operational Taxonomic Unit composition of stool samples according to the nutritional status	Baseline, three and six months after inclusion	Each sample will be ADN extracted using Quiagen technology 16S and 18S amplification will be conducted following Hughert et al. (2014) and Tang et al. (2015). PCR products will be sequenced using NGS Illumina plateform. Sequences will be analyzed using Mothur 1.37.6 software and Silva data base (https://www.arb-silva.de/browser). OTU (Operational Taxonomic Unit) composition will be determined for each sample.; OTU composition of samples from well and malnourished children will be compared using mann whitney test, and shift in OTUs during renutrition will be analysed using survival analysis.
Cognitive-motor development (Senegal)	Baseline, three, six and nine months after inclusion	Developmental Milestones Checklist II (DMC II) questionnaire to evaluate participating children cognitive and motor abilities.

Trial Locations

Locations (4)

Institut Pasteur de bangui - Centre Nutritionnel de Gbangouma et Centre de Santé Saint-Joseph; 🇨🇫 Bangui, Central African Republic

Institut Pasteur de Madagascar - CRENAM Andohotapenaka et Centre de Santé Mitia; 🇲🇬 Antananarivo, Madagascar

Centre de santé intégré ACF de Tchake et d'Issawanne; 🇳🇪 Maradi, Niger

Institut Pasteur de Dakar - Poste de Santé Hamo V; 🇸🇳 Dakar, Guédiawaye, Senegal