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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03268902
Other study ID # 19465
Secondary ID
Status Completed
Phase Phase 2/Phase 3
First received
Last updated
Start date September 5, 2017
Est. completion date March 26, 2020

Study information

Verified date April 2021
Source Haydom Lutheran Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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 information / eligibility

Status Completed
Enrollment 1188
Est. completion date March 26, 2020
Est. primary completion date February 28, 2020
Accepts healthy volunteers No
Gender All
Age group N/A to 14 Days
Eligibility Inclusion Criteria: 1. Maternal age =18 2. Infant = 14 days Exclusion Criteria: 1. Maternal inability to adhere to protocol 2. Multiple gestation 3. Severe illness (significant birth defect, hospitalization, severe neonatal illness) 4. Birth weight <1500 g 5. Lack of breastfeeding at enrollment (and lack of intention to continue breastfeeding at time of enrollment).

Study Design


Intervention

Drug:
Azithromycin Oral Liquid Product
Azithromycin 20 mg/kg administered by study personnel at 6, 9, 12 and 15 months
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

Locations

Country Name City State
Tanzania Haydom Lutheran Hospital Haydom Manyara

Sponsors (3)

Lead Sponsor Collaborator
Haydom Lutheran Hospital Bill and Melinda Gates Foundation, University of Virginia

Country where clinical trial is conducted

Tanzania, 

Outcome

Type Measure Description Time frame Safety issue
Primary Height-for-age z-score (HAZ) at 18 months 18 months
Secondary Weight-for-age z-score (WAZ) at 18 months 18 months
Secondary Head circumference-for-age z-score (HCAZ) at 18 months 18 months
Secondary Stunting HAZ <-2 18 months
Secondary All cause mortality 0-18 months
Secondary Hospitalization 0-18 months
Secondary Childhood illness Incidence of diarrhea, lower respiratory infection and febrile illness 0-18 months
Secondary Anemia Moderate to severe anemia by WHO definition for age and altitude 12 and 18 months
Secondary Enteropathogen burden 6, 6.5, 12, 12.5, 18 months
Secondary Microbiota composition Composition of intestinal microbiome 6, 6.5, 12, 18 months
Secondary Stool myeloperoxidase concentration Stool myeloperoxidase ELISA 6, 12, 18 months
Secondary C-reactive protein concentration in serum High-sensitivity CRP concentration 12 and 18 months
Secondary Insulin-like growth factor 1 concentration in serum 12 and 18 months
Secondary Collagen X concentration in serum 12 and 18 months
Secondary Tryptophan-kynurenine ratio Ratio of tryptophan concentration to kynurenine concentration in metabolomic testing 12 and 18 months
Secondary Niacin and nicotinamide metabolite concentration Concentration of downstream metabolites of niacin and nicotinamide as tested by metabolomic analysis 6, 12, 18 months
Secondary Small intestinal bacterial overgrowth Prevalence of SIBO as tested via exhaled hydrogen 6, 12 and 18 months
Secondary Malawi Developmental Assessment Tool score The MDAT is a measure of child cognitive development 18 months
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