A Phase 2/3 interventional study of Azithromycin Oral Liquid Product and Nitazoxanide Oral Suspension in Malnutrition, Stunting and Cognitive Development, sponsored by Haydom Lutheran Hospital. Completed at 1 site in Tanzania. Open to participants aged 0 Days to 14 Days. Per ClinicalTrials.gov, last updated 2021-05-10.
Sponsored by Haydom Lutheran Hospital · Phase 2/3, Interventional, and Treatment
This study aims to assess growth and cognitive effects of treatment with azithromycin and nitazoxanide and/or nicotinamide (vitamin B3) supplementation nicotinamide.
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.
Exclusion Criteria:
Nicotinamide Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension
Drug: Azithromycin Oral Liquid Product · Drug: Nitazoxanide Oral Suspension · Dietary Supplement: Nicotinamide
Placebo Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension
Drug: Azithromycin Oral Liquid Product · Drug: Nitazoxanide Oral Suspension · Drug: Placebos
Nicotinamide Placebo Placebo
Dietary Supplement: Nicotinamide · Drug: Placebos
Placebo Placebo Placebo
Drug: Placebos
Azithromycin 20 mg/kg administered by study personnel at 6, 9, 12 and 15 months
Also known as: Throza DPS
Nitazoxanide 100 mg given twice daily for 3 days at 12 and 15 months
Also known as: Alinia
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
Also known as: Vitamin B3
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
Height-for-age z-score (HAZ) at 18 months
Time frame: 18 months
Weight-for-age z-score (WAZ) at 18 months
Time frame: 18 months
Head circumference-for-age z-score (HCAZ) at 18 months
Time frame: 18 months
Stunting
HAZ \<-2
Time frame: 18 months
All cause mortality
Time frame: 0-18 months
Hospitalization
Time frame: 0-18 months
Childhood illness
Incidence of diarrhea, lower respiratory infection and febrile illness
Time frame: 0-18 months
Anemia
Moderate to severe anemia by WHO definition for age and altitude
Time frame: 12 and 18 months
Enteropathogen burden
Time frame: 6, 6.5, 12, 12.5, 18 months
Microbiota composition
Composition of intestinal microbiome
Time frame: 6, 6.5, 12, 18 months
Stool myeloperoxidase concentration
Stool myeloperoxidase ELISA
Time frame: 6, 12, 18 months
C-reactive protein concentration in serum
High-sensitivity CRP concentration
Time frame: 12 and 18 months
Insulin-like growth factor 1 concentration in serum
Time frame: 12 and 18 months
Collagen X concentration in serum
Time frame: 12 and 18 months
Tryptophan-kynurenine ratio
Ratio of tryptophan concentration to kynurenine concentration in metabolomic testing
Time frame: 12 and 18 months
Niacin and nicotinamide metabolite concentration
Concentration of downstream metabolites of niacin and nicotinamide as tested by metabolomic analysis
Time frame: 6, 12, 18 months
Small intestinal bacterial overgrowth
Prevalence of SIBO as tested via exhaled hydrogen
Time frame: 6, 12 and 18 months
Malawi Developmental Assessment Tool score
The MDAT is a measure of child cognitive development
Time frame: 18 months
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Plan to share: No
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Haydom Lutheran Hospital