Early Life Interventions for Childhood Growth and Development In Tanzania (ELICIT)

Haydom Lutheran Hospital

Status and phase: Completed; Phase 3; Phase 2

Conditions: Cognitive Development; Malnutrition; Stunting; Enteric Pathogens

Treatments: Drug: Azithromycin Oral Liquid Product; Drug: Nitazoxanide Oral Suspension; Dietary Supplement: Nicotinamide; Drug: Placebos

Study type: Interventional

Funder types: Other

Identifiers

NCT03268902

19465

Details and patient eligibility

About

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

Full 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.

Enrollment: 1,188 patients

Sex: All

Ages: Under 14 days old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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1,188 participants in 4 patient groups, including a placebo group

Nicotinamide and Antimicrobials

Experimental group

Description:

Nicotinamide Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension

Treatment:

Dietary Supplement: Nicotinamide

Drug: Nitazoxanide Oral Suspension

Drug: Azithromycin Oral Liquid Product

Antimicrobials only

Experimental group

Description:

Placebo Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension

Treatment:

Drug: Nitazoxanide Oral Suspension

Drug: Placebos

Drug: Azithromycin Oral Liquid Product

Nicotinamide only

Experimental group

Description:

Nicotinamide Placebo Placebo

Treatment:

Dietary Supplement: Nicotinamide

Drug: Placebos

No active treatment

Placebo Comparator group

Description:

Placebo Placebo Placebo

Treatment:

Drug: Placebos