Early Life Interventions for Childhood Growth and Development In Tanzania
- Conditions
- MalnutritionStuntingCognitive DevelopmentEnteric Pathogens
- Interventions
- Dietary Supplement: NicotinamideDrug: Placebos
- Registration Number
- NCT03268902
- Lead Sponsor
- Haydom Lutheran Hospital
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1188
- Maternal age ≥18
- Infant ≤ 14 days
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Nicotinamide and Antimicrobials Azithromycin Oral Liquid Product Nicotinamide Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension Nicotinamide and Antimicrobials Nitazoxanide Oral Suspension Nicotinamide Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension Nicotinamide and Antimicrobials Nicotinamide Nicotinamide Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension Antimicrobials only Azithromycin Oral Liquid Product Placebo Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension Antimicrobials only Nitazoxanide Oral Suspension Placebo Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension Antimicrobials only Placebos Placebo Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension Nicotinamide only Nicotinamide Nicotinamide Placebo Placebo Nicotinamide only Placebos Nicotinamide Placebo Placebo No active treatment Placebos Placebo Placebo Placebo
- Primary Outcome Measures
Name Time Method Height-for-age z-score (HAZ) at 18 months 18 months
- Secondary Outcome Measures
Name Time Method Stunting 18 months HAZ \<-2
All cause mortality 0-18 months Weight-for-age z-score (WAZ) at 18 months 18 months Head circumference-for-age z-score (HCAZ) at 18 months 18 months Hospitalization 0-18 months Childhood illness 0-18 months Incidence of diarrhea, lower respiratory infection and febrile illness
Anemia 12 and 18 months Moderate to severe anemia by WHO definition for age and altitude
Enteropathogen burden 6, 6.5, 12, 12.5, 18 months Microbiota composition 6, 6.5, 12, 18 months Composition of intestinal microbiome
Stool myeloperoxidase concentration 6, 12, 18 months Stool myeloperoxidase ELISA
C-reactive protein concentration in serum 12 and 18 months High-sensitivity CRP concentration
Insulin-like growth factor 1 concentration in serum 12 and 18 months Collagen X concentration in serum 12 and 18 months Tryptophan-kynurenine ratio 12 and 18 months Ratio of tryptophan concentration to kynurenine concentration in metabolomic testing
Niacin and nicotinamide metabolite concentration 6, 12, 18 months Concentration of downstream metabolites of niacin and nicotinamide as tested by metabolomic analysis
Small intestinal bacterial overgrowth 6, 12 and 18 months Prevalence of SIBO as tested via exhaled hydrogen
Malawi Developmental Assessment Tool score 18 months The MDAT is a measure of child cognitive development
Trial Locations
- Locations (1)
Haydom Lutheran Hospital
🇹🇿Haydom, Manyara, Tanzania