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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03268902
Recruitment Status : Completed
First Posted : August 31, 2017
Last Update Posted : May 10, 2021
Sponsor:
Collaborators:
University of Virginia
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Haydom Lutheran Hospital

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

Condition or disease Intervention/treatment Phase
Malnutrition Stunting Cognitive Development Enteric Pathogens Drug: Azithromycin Oral Liquid Product Drug: Nitazoxanide Oral Suspension Dietary Supplement: Nicotinamide Drug: Placebos Phase 2 Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1188 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description: Each intervention will be assigned independently. Intervention domains will be randomized separately on an individual basis. This will provide 4 different combinations of interventions: 1). Nicotinamide, azithromycin and nitazoxanide 2). Azithromycin and nitazoxanide 3). Nicotinamide only 4). No active treatment.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Both participants and investigators will be blinded to the treatments allocated to each participant. The members of the DSMB will also be blinded.
Primary Purpose: Treatment
Official Title: Early Life Interventions for Childhood Growth and Development In Tanzania
Actual Study Start Date : September 5, 2017
Actual Primary Completion Date : February 28, 2020
Actual Study Completion Date : March 26, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Nicotinamide and Antimicrobials
Nicotinamide Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension
 Drug: Azithromycin Oral Liquid Product
Azithromycin 20 mg/kg administered by study personnel at 6, 9, 12 and 15 months
Other Name: Throza DPS

Drug: Nitazoxanide Oral Suspension
Nitazoxanide 100 mg given twice daily for 3 days at 12 and 15 months
Other Name: Alinia

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

Other Name: Vitamin B3
Experimental: Antimicrobials only
Placebo Azithromycin Oral Liquid Product Nitazoxanide Oral Suspension
 Drug: Azithromycin Oral Liquid Product
Azithromycin 20 mg/kg administered by study personnel at 6, 9, 12 and 15 months
Other Name: Throza DPS

Drug: Nitazoxanide Oral Suspension
Nitazoxanide 100 mg given twice daily for 3 days at 12 and 15 months
Other Name: Alinia

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
Experimental: Nicotinamide only
Nicotinamide Placebo Placebo
 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

Other Name: Vitamin B3

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
Placebo Comparator: No active treatment
Placebo Placebo Placebo
 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


Outcome Measures
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Primary Outcome Measures :
  1. Height-for-age z-score (HAZ) at 18 months [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. Weight-for-age z-score (WAZ) at 18 months [ Time Frame: 18 months ]
  2. Head circumference-for-age z-score (HCAZ) at 18 months [ Time Frame: 18 months ]
  3. Stunting [ Time Frame: 18 months ]
    HAZ <-2

  4. All cause mortality [ Time Frame: 0-18 months ]
  5. Hospitalization [ Time Frame: 0-18 months ]
  6. Childhood illness [ Time Frame: 0-18 months ]
    Incidence of diarrhea, lower respiratory infection and febrile illness

  7. Anemia [ Time Frame: 12 and 18 months ]
    Moderate to severe anemia by WHO definition for age and altitude

  8. Enteropathogen burden [ Time Frame: 6, 6.5, 12, 12.5, 18 months ]
  9. Microbiota composition [ Time Frame: 6, 6.5, 12, 18 months ]
    Composition of intestinal microbiome

  10. Stool myeloperoxidase concentration [ Time Frame: 6, 12, 18 months ]
    Stool myeloperoxidase ELISA

  11. C-reactive protein concentration in serum [ Time Frame: 12 and 18 months ]
    High-sensitivity CRP concentration

  12. Insulin-like growth factor 1 concentration in serum [ Time Frame: 12 and 18 months ]
  13. Collagen X concentration in serum [ Time Frame: 12 and 18 months ]
  14. Tryptophan-kynurenine ratio [ Time Frame: 12 and 18 months ]
    Ratio of tryptophan concentration to kynurenine concentration in metabolomic testing

  15. Niacin and nicotinamide metabolite concentration [ Time Frame: 6, 12, 18 months ]
    Concentration of downstream metabolites of niacin and nicotinamide as tested by metabolomic analysis

  16. Small intestinal bacterial overgrowth [ Time Frame: 6, 12 and 18 months ]
    Prevalence of SIBO as tested via exhaled hydrogen

  17. Malawi Developmental Assessment Tool score [ Time Frame: 18 months ]
    The MDAT is a measure of child cognitive development


Eligibility Criteria
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Ages Eligible for Study:   0 Days to 14 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03268902


Locations
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Tanzania
Haydom Lutheran Hospital
Haydom, Manyara, Tanzania
Sponsors and Collaborators
Haydom Lutheran Hospital
University of Virginia
Bill and Melinda Gates Foundation
Investigators
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Principal Investigator: Estomih Mduma Haydom Lutheran Hospital
  Study Documents (Full-Text)

Documents provided by Haydom Lutheran Hospital:
Statistical Analysis Plan  [PDF] February 5, 2020

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Haydom Lutheran Hospital
ClinicalTrials.gov Identifier: NCT03268902    
Other Study ID Numbers: 19465
First Posted: August 31, 2017    Key Record Dates
Last Update Posted: May 10, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Malnutrition
Nutrition Disorders
Niacinamide
Niacin
Nicotinic Acids
Azithromycin
Nitazoxanide
Vitamins
Micronutrients
Physiological Effects of Drugs
 Anti-Bacterial Agents
Anti-Infective Agents
Vitamin B Complex
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents
Antiparasitic Agents