NCT03268902

Early Life Interventions for Childhood Growth and Development In Tanzania

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 1,188 (actual)
• Sponsor: Haydom Lutheran Hospital · Academic / Other
• Sex: All
• Age: 0 Days – 14 Days
• Healthy volunteers: Not accepted

Summary

This study aims to assess growth and cognitive effects of treatment with azithromycin and nitazoxanide and/or nicotinamide (vitamin B3) supplementation nicotinamide.

Detailed description

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.

Conditions

• Malnutrition
• Stunting
• Cognitive Development
• Enteric Pathogens

Interventions

Type	Name	Description
DRUG	Azithromycin Oral Liquid Product	Azithromycin 20 mg/kg administered by study personnel at 6, 9, 12 and 15 months
DRUG	Nitazoxanide Oral Suspension	Nitazoxanide 100 mg given twice daily for 3 days at 12 and 15 months
DIETARY_SUPPLEMENT	Nicotinamide	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
DRUG	Placebos	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

Timeline

• Start date: 2017-09-05
• Primary completion: 2020-02-28
• Completion: 2020-03-26
• First posted: 2017-08-31
• Last updated: 2021-05-10

Locations

1 site across 1 country: Tanzania

Regulatory

• FDA-regulated drug study