Official Title
Early Life Interventions for Childhood Growth and Development In Tanzania
Phase
Phase 2/Phase 3Lead Sponsor
Haydom Lutheran HospitalStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Malnutrition Stunting Cognitive Development Enteric PathogensIntervention/Treatment
Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension Nicotinamide ...Study Participants
1188This study aims to assess growth and cognitive effects of treatment with azithromycin and nitazoxanide and/or nicotinamide (vitamin B3) supplementation nicotinamide.
Children living in rural sub-Saharan Africa experience massive challenges to child thriving, with poor linear growth and delays in child development. In a cohort of 211 children living in the rural Haydom area of Tanzania (participating in the Interactions of Malnutrition & Enteric Infections: Consequences for Child Health and Development "MAL-ED" Study), 70.6% had stunted growth at 18 months. This rate of moderate and severe stunting (length-for-age z-score [HAZ] <-2 standard deviations) was the highest of the 8 study sites in MAL-ED.
This enormous deficit is likely associated with high rates of enteric infections with Campylobacter, E. coli pathotypes, Cryptosporidium, and Giardia, organisms susceptible to azithromycin and/or nitazoxanide. Infections such as these occur frequently in developing areas and are often associated with environmental enteropathy, including ongoing enteric inflammation and loss of enterocyte integrity, leading to possible bacterial translocation and poorer absorption of ingested nutrients. The consequences of these infections, enteric dysfunction and poor nutrient absorption frequently include growth stunting, learning delays, and an overall loss of human capital.
Emerging evidence suggests a potential role for the tryptophan-niacin pathway (including the end-product nicotinamide, an isoform of vitamin B3) in decreasing mucosal inflammation and affecting enteral microbiota. At the Tanzania site of MAL-ED, serum levels of tryptophan were related to subsequent linear growth, further suggesting importance of the tryptophan-niacin pathway. What is not clear is whether early childhood growth and development could be improved by targeting enteric infection and the tryptophan-niacin pathway by 1) delivering antibiotics against specific bacteria and/or 2) providing vitamin B3 as nicotinamide/niacinamide.
The main analysis will be intention-to-treat but a secondary analysis will be per protocol.
Azithromycin 20 mg/kg administered by study personnel at 6, 9, 12 and 15 months
Nitazoxanide 100 mg given twice daily for 3 days at 12 and 15 months
Mothers in the nicotinamide arm will be given nicotinamide 250 mg daily from delivery through 6 months post-partum in capsule form. Children in the nicotinamide arm will be given 100 mg/d in powder form between 6 and 18 months of age
Contain inert excipients only. Azithromycin placebo 20 mg/kg administered by study personnel at 6, 9, 12 and 15 months. Nitazoxanide placebo 100 mg given twice daily for 3 days at 12 and 15 months. Mothers in the nicotinamide placebo arm will be given placebo 250 mg daily from delivery through 6 months post-partum in capsule form. Children in the nicotinamide placebo arm will be given 100 mg/d of placebo in powder form between 6 and 18 months of age
Nicotinamide Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension
Placebo Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension
Nicotinamide Placebo Placebo
Inclusion Criteria: Maternal age ≥18 Infant ≤ 14 days Exclusion Criteria: Maternal inability to adhere to protocol Multiple gestation Severe illness (significant birth defect, hospitalization, severe neonatal illness) Birth weight <1500 g Lack of breastfeeding at enrollment (and lack of intention to continue breastfeeding at time of enrollment).
