Three‐arm clinical trial of improved flour targeting intestinal microbiota (MALINEA)

• Published in: Maternal and child nutrition Vol. 20; no. 3; pp. e13649 - n/a
• Main Authors: Vray, Muriel, Tondeur, Laura, Hedible, Boris G., Randremanana, Rindra Vatosoa, Manirakiza, Alexandre, Lazoumar, Ramatoulaye Hamidou, Platen, Cassandre Van, Vargas, Antonio, Briend, André, Jambou, Ronan, Andrianantenaina, Rado Ernestau Marice, Andrianomenjanahary, Nirina Nadia, Barry, Oumar, Batoumbou, Yvette, Buttarelli, Emilie, Carbonne, Fabrice, Djibo, Ousmane Moussa, Dougnon, Abdias Ogobara, Gado, Abdal‐Aziz Ousma, Diop, Mareme Gaye, Gnocchi, Viola, Gody, Jean‐Chrysostome, Kane, Dieynaba, Lombart, Jean‐Pierre, Mamane, Sani, Maronne, Dior, Ndongo, Youmou, Nguiamba, Deborah, Oumarou, Garda Ide, Rabemiafara, Hobitiana Marietta, Rafanomezantsoa, Antsanirina Sitrakantenaina, Andrianaly, Voahanginirina Rakotoarimivo, Rakotondramanana, Rojovola, Randriamparany, Ravaka, Randrianarisoa, Christelle Mioranirina, Rasetamalala, Ratrimonirina, Hanta Viviane, Razanarimanana, Marie‐Florence, Sakanga, Olga, Sarr, Auguste, Seck, Abdoulaye, Sy, Aminata, Voarinirina, Tokiravakiniaina
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.07.2024; Wiley; John Wiley and Sons Inc
• Subjects: Age; Anti-Bacterial Agents - administration & dosage; Antibiotics; Azithromycin - administration & dosage; Bacteria; Central African Republic; Child, Preschool; Children; Children & youth; Clinical research; Clinical trials; Community health care; Diarrhea; Edema; Female; Flour; Food, Fortified; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - physiology; Humans; Infant; Infections; Inulin - administration & dosage; Life Sciences; Madagascar; Male; Males; Malnutrition; Microbiology and Parasitology; Microbiota; Niger; Nutrition; Oligosaccharides - administration & dosage; Original; Parasitology; prebiotic; Prebiotics; Prebiotics - administration & dosage; Senegal; Suspension; Senegal; Niger; Madagascar; microbiota; malnutrition; Niger; Senegal; Madagascar; Central African Republic; prebiotic
• ISSN: 1740-8695; 1740-8709; 1740-8709
• DOI: 10.1111/mcn.13649

The main objective of this project was to compare in the field conditions two strategies of re‐nutrition of children with moderate acute malnutrition (MAM) aged from 6 to 24 months, targeting the microbiota in comparison with a standard regimen. A three‐arm, open‐label, pragmatic randomised trial was conducted in four countries (Niger, CAR, Senegal and Madagascar). Children received for 12 weeks either fortified blended flour (FBF control) = arm 1, or FBF + azithromycin (oral suspension of 20 mg/kg/day daily given with a syringe) for the first 3 days at inclusion = arm 2 or mix FBF with inulin/fructo‐oligosaccharides (6 g/day if age ≥12 months and 4 g if age <12 months) = arm 3. For each arm, children aged from 6 to 11 months received 100 g x 2 per day of flours and those aged from 12 to 24 months received 100 g × 3 per day of FBF. The primary endpoint was nutritional recovery, defined by reaching a weight‐for‐height z‐score (WHZ) ≥ −1.5 within 12 weeks. Overall, 881 children were randomised (297, 290 and 294 in arm 1, arm 2 and arm 3, respectively). Three hundred and forty‐four children were males (39%) and median/mean age were 14.6/14.4 months (SD = 4.9, IQR = 10.5–18.4). At inclusion, the three arms were comparable for all criteria, but differences were observed between countries. Overall, 44% (390/881) of the children recovered at week 12 from MAM, with no significant difference between the three arms (41.4%, 45.5% and 45.9%, in arm 1, arm 2 and arm 3, respectively, p = 0.47). This study did not support the true advantages of adding a prebiotic or antibiotic to flour. When using a threshold of WHZ ≥ −2 as an exploratory endpoint, significant differences were observed between the three arms, with higher success rates in arms with antibiotics or prebiotics compared to the control arm (66.9%, 66.0% and 55.2%, respectively, p = 0.005). This open‐label randomised trial, conducted in the field conditions with locally produced supplements in 881 children with moderate acute malnutrition in four African countries, did not support the true advantages of adding a prebiotic or a treatment with antibiotic to flour in that it did not achieve, as it failed to meet the primary endpoint retained, that is, WHZ ≥ −1.5. †No successive visits at Week‐12; Lost to follow‐up at week‐12; Missing data at Week‐12; Other (Two maternal deaths, 1 mother's inability to continue the study and one case of flour refusal of the child) Arm 1: daily Fortified Blended Flour; Arm 2; daily Fortified Blended Flour + azithromycin; Arm 3: daily Fortified Blended Flour containing inulin/Fructo‐oligosaccharides Key messages Re‐nutrition of children with MAM is still a concern as the duration of recovery is always long and recurrences are frequent. Literature suggests that prebiotics and antibiotics show potentially useful properties to speed this process of recovery. However, in this open‐label study, prebiotics and antibiotics did not lead to advantages on the recovery rates defined by reaching the WHZ (−1.5) cut‐off.