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

A Multi-center, Randomized Controlled Comparison of Three Renutrition Strategies for the Management of Moderate Acute Malnutrition Among Children From 6 to 24 Months (Madagascar, Niger, Central African Republic and Senegal)

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.

Study Overview

• Status: Completed
• Conditions: Moderate Acute Malnutrition
• Intervention / Treatment: Drug: Albendazole; Dietary supplement: Fortified blend flour; Drug: Azythromycin; Dietary supplement: Inuline and fructo-oligosaccharides

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 Type: Interventional
• Enrollment (Actual): 1357
• Phase: Phase 3

Contacts and Locations

Study Locations

• Central African Republic
  • Bangui, Central African Republic, BP 923
    • Institut Pasteur de bangui - Centre Nutritionnel de Gbangouma et Centre de Santé Saint-Joseph
• Madagascar
  • Antananarivo, Madagascar, 101
    • Institut Pasteur de Madagascar - CRENAM Andohotapenaka et Centre de Santé Mitia
• Niger
  • Maradi, Niger
    • Centre de santé intégré ACF de Tchake et d'Issawanne
• Senegal
  • Guédiawaye
    • Dakar, Guédiawaye, Senegal
      • Institut Pasteur de Dakar - Poste de Santé Hamo V

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; 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.	Drug: Albendazole; Administration of Albendazole at inclusion of the child : 200mgs, one administration; Other Names: Antiparasitic drug; Dietary supplement: Fortified blend flour; Children from 6 to 11 months : 200 grams / day Children from 12 to 24 months : 300 grams / day Compostion of the fortified blend flour per 100 grams : either : Mil (whole grains): 58,56 g/100g, Soybeans (fat meal): 16,54g/100g Peanuts (roasted seeds): 8,75g/100g, Cane sugar: 7,35 g/100g Whole milk (Powder): 7,56g/100g, MSV MAM: 0,28g/100g, iodized salt :0,45g/100g, CaC03: 0,48g/100g,Amylase BAN: 0,03g/100g OR Corn (whole grains): 53,29g/100g, Soybeans (dry seeds): 17,82g/100g, Peanuts (roasted seeds): 9,00 g/100g, Cane sugar: 11,00 Whole milk (Powder): 5,00g/100g, Soybean Oil (Purified): 1,24g/100g, Peanut oil (Purified): 1,13g/100g, MSV MAM: 0,27g/100g, iodized salt: 0,53 g/100g, Ca3(PO4)2: 0,62g/100g, KCl: 0,09g/100g; Other Names: Lacteal flour
Active Comparator: 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.	Drug: Albendazole; Administration of Albendazole at inclusion of the child : 200mgs, one administration; Other Names: Antiparasitic drug; Dietary supplement: Fortified blend flour; Children from 6 to 11 months : 200 grams / day Children from 12 to 24 months : 300 grams / day Compostion of the fortified blend flour per 100 grams : either : Mil (whole grains): 58,56 g/100g, Soybeans (fat meal): 16,54g/100g Peanuts (roasted seeds): 8,75g/100g, Cane sugar: 7,35 g/100g Whole milk (Powder): 7,56g/100g, MSV MAM: 0,28g/100g, iodized salt :0,45g/100g, CaC03: 0,48g/100g,Amylase BAN: 0,03g/100g OR Corn (whole grains): 53,29g/100g, Soybeans (dry seeds): 17,82g/100g, Peanuts (roasted seeds): 9,00 g/100g, Cane sugar: 11,00 Whole milk (Powder): 5,00g/100g, Soybean Oil (Purified): 1,24g/100g, Peanut oil (Purified): 1,13g/100g, MSV MAM: 0,27g/100g, iodized salt: 0,53 g/100g, Ca3(PO4)2: 0,62g/100g, KCl: 0,09g/100g; Other Names: Lacteal flour; Drug: Azythromycin; Administration of azythromycin to the child at inclusion (3 days) 20 mgs/kgs/day : three days; Other Names: Antibiotics
Active Comparator: Prebiotic; 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)	Drug: Albendazole; Administration of Albendazole at inclusion of the child : 200mgs, one administration; Other Names: Antiparasitic drug; Dietary supplement: Fortified blend flour; Children from 6 to 11 months : 200 grams / day Children from 12 to 24 months : 300 grams / day Compostion of the fortified blend flour per 100 grams : either : Mil (whole grains): 58,56 g/100g, Soybeans (fat meal): 16,54g/100g Peanuts (roasted seeds): 8,75g/100g, Cane sugar: 7,35 g/100g Whole milk (Powder): 7,56g/100g, MSV MAM: 0,28g/100g, iodized salt :0,45g/100g, CaC03: 0,48g/100g,Amylase BAN: 0,03g/100g OR Corn (whole grains): 53,29g/100g, Soybeans (dry seeds): 17,82g/100g, Peanuts (roasted seeds): 9,00 g/100g, Cane sugar: 11,00 Whole milk (Powder): 5,00g/100g, Soybean Oil (Purified): 1,24g/100g, Peanut oil (Purified): 1,13g/100g, MSV MAM: 0,27g/100g, iodized salt: 0,53 g/100g, Ca3(PO4)2: 0,62g/100g, KCl: 0,09g/100g; Other Names: Lacteal flour; Dietary supplement: Inuline and fructo-oligosaccharides; Administration of inuline and fructo-oligosaccharides (Synergy1) 2g/day, mixed with the fortified blend flour given to the child through the whole intervention.; Other Names: Prebiotic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery at 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	Three month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive-motor development (Senegal)	Developmental Milestones Checklist II (DMC II) questionnaire to evaluate participating children cognitive and motor abilities.	Baseline, three, six and nine months after inclusion
Comparison of the Operational Taxonomic Unit composition of stool samples according to the nutritional status	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.	Baseline, three and six months after inclusion

Collaborators and Investigators

• Sponsor: Institut Pasteur
• Collaborators: Institut Pasteur de Madagascar; Action Contre la Faim; Centre de Recherches Médicales et Sanitaires CERMES Niger; Institut Pasteur de Bangui; Institut Pasteur de Dakar
• Investigators: Principal Investigator: Ronan JAMBOU, PhD, Institut Pasteur; Principal Investigator: Muriel Vray, phD, Institut Pasteur

Publications and helpful links

General Publications

• Vray M, Hedible BG, Adam P, Tondeur L, Manirazika A, Randremanana R, Mainassara H, Briend A, Artaud C, von Platen C, Altmann M, Jambou R. A multicenter, randomized controlled comparison of three renutrition strategies for the management of moderate acute malnutrition among children aged from 6 to 24 months (the MALINEA project). Trials. 2018 Dec 4;19(1):666. doi: 10.1186/s13063-018-3027-3. Erratum In: Trials. 2019 Apr 11;20(1):211.

Helpful Links

• GRET: French development NGO fighting poverty and inequalities, providing solutions for development [150 projects per year in 30 countries]
• Institut Pasteur: Private non-profit foundation whose mission is to prevent and treat diseases through research, teaching, and public health initiatives.
• Action contre la faim [Action against hunger] : International humanitarian organization providing communities with access to safe water and sustainable solutions to hunger.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2018
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: June 13, 2016
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (Actual): March 22, 2018

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Children; Prebiotic; Randomized Controlled Trial; Cognitive impairment; Azithromycin; Africa; Pragmatic trial; Metagenomic
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiprotozoal Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Anti-Bacterial Agents; Azithromycin; Albendazole; Antiparasitic Agents
• Other Study ID Numbers: 2014-062; FPC N° 2013-4025 (Other Grant/Funding Number: Ministère de l'Europe et des Affaires Etrangères)

Drug and device information, study documents

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