Early Life Interventions for Childhood Growth and Development In Tanzania

Malnutrition Clinical Trial

— ELICIT  

Official title:

Early Life Interventions for Childhood Growth and Development In Tanzania

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03268902
• Other study ID #: 19465
• Status: Completed
• Phase: Phase 2/Phase 3
• 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
• 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).

Related Conditions & MeSH terms

• Cognitive Development
• Enteric Pathogens
• Malnutrition
• Stunting

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