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CompletedNCT03474276MALINEAUpdated May 24, 2022

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

A Phase 3 interventional study of Azythromycin and Inuline and fructo-oligosaccharides in Moderate Acute Malnutrition, sponsored by Institut Pasteur. Completed at 4 sites in 4 countries. Open to participants aged 6 Months to 24 Months, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-05-24.

Sponsored by Institut Pasteur · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,357
Allocation
Randomized
Ages
6 Months to 24 Months
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Moderate Acute Malnutrition

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Keywords

  • Children
  • Africa
  • Metagenomic
  • Prebiotic
  • Randomized Controlled Trial
  • Pragmatic trial
  • Azithromycin
  • Cognitive impairment
03

Who can participate

Ages eligible
6 Months to 24 Months
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
1,357 participants (actual)

Study arms

  • 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 · Dietary Supplement: Fortified blend 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: Azythromycin · Drug: Albendazole · Dietary Supplement: Fortified blend flour

  • 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)

    Dietary Supplement: Inuline and fructo-oligosaccharides · Drug: Albendazole · Dietary Supplement: Fortified blend flour

Interventions

  • DrugAzythromycin

    Administration of azythromycin to the child at inclusion (3 days) 20 mgs/kgs/day : three days

    Also known as: Antibiotics

  • Dietary supplementInuline 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.

    Also known as: Prebiotic

  • DrugAlbendazole

    Administration of Albendazole at inclusion of the child : 200mgs, one administration

    Also known as: Antiparasitic drug

  • Dietary supplementFortified 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

    Also known as: Lacteal flour

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: Three month

Secondary outcomes

  1. Cognitive-motor development (Senegal)

    Developmental Milestones Checklist II (DMC II) questionnaire to evaluate participating children cognitive and motor abilities.

    Time frame: Baseline, three, six and nine months after inclusion

  2. 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.

    Time frame: Baseline, three and six months after inclusion

06

Study locations

4 sites
  • Institut Pasteur de bangui - Centre Nutritionnel de Gbangouma et Centre de Santé Saint-Joseph
    Bangui, BP 923, Central African Republic
  • Institut Pasteur de Madagascar - CRENAM Andohotapenaka et Centre de Santé Mitia
    Antananarivo, 101, 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
07

References and documents

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. doi: 10.1186/s13063-019-3339-y. PubMed 30514364 ↗
08

Registry details

Key details

Study ID
NCT03474276
Lead sponsor
Institut Pasteur
Collaborators
Action Contre la Faim, Centre de Recherches Médicales et Sanitaires CERMES Niger, Institut Pasteur de Madagascar, Institut Pasteur de Bangui, Institut Pasteur de Dakar
Responsible party
Sponsor
First posted
Mar 22, 2018
Start date
Jan 31, 2018
Primary completion
Dec 31, 2018
Completion
Jun 30, 2019
Last update
May 24, 2022

Study contacts

Ronan JAMBOU, PhD
principal investigator · Institut Pasteur
Muriel Vray, phD
principal investigator · Institut Pasteur

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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