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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Moderate Acute Malnutrition

Intervention / Treatment
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* Drug: Azythromycin
* Dietary Supplement: Inuline and fructo-oligosaccharides
* Drug: Albendazole
* Dietary Supplement: Fortified blend flour


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>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<br>* Administration of Albendazole at inclusion of the child : 200mgs, one administration<br>* Other names: Antiparasitic drug;Dietary Supplement: Fortified blend flour<br>* 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<br>* Other names: Lacteal flour;|
| Active Comparator: Azythromycin<br>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: Azythromycin<br>* Administration of azythromycin to the child at inclusion (3 days) 20 mgs/kgs/day : three days<br>* Other names: Antibiotics;Drug: Albendazole<br>* Administration of Albendazole at inclusion of the child : 200mgs, one administration<br>* Other names: Antiparasitic drug;Dietary Supplement: Fortified blend flour<br>* 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<br>* Other names: Lacteal flour;|
| Active Comparator: Prebiotic<br>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) | Dietary Supplement: Inuline and fructo-oligosaccharides<br>* Administration of inuline and fructo-oligosaccharides (Synergy1) 2g/day, mixed with the fortified blend flour given to the child through the whole intervention.<br>* Other names: Prebiotic;Drug: Albendazole<br>* Administration of Albendazole at inclusion of the child : 200mgs, one administration<br>* Other names: Antiparasitic drug;Dietary Supplement: Fortified blend flour<br>* 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<br>* Other names: Lacteal flour;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children, Africa, Metagenomic, Prebiotic, Randomized Controlled Trial, Pragmatic trial, Azithromycin, Cognitive impairment