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Protein Plus: Improving Infant Growth Through Diet and Enteric Health

Efficacy of Supplemental Protein, Delivered Alone or in Combination With Treatment for Enteric Pathogens, to Prevent Growth Faltering in Bangladeshi Infants

Status
Completed
Phases
Phase 2Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03683667
Acronym
JiVitA-6
Enrollment
5283
Registered
2018-09-25
Start date
2018-09-23
Completion date
2020-03-24
Last updated
2022-12-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Stunting, Malnutrition; Protein, Enteric Pathogens, Campylobacter Infections

Keywords

linear growth, infant feeding, environmental enteric dysfunction

Brief summary

This cluster-randomized controlled trial is designed to address linear growth faltering in 6-12-mo-old Bangladesh infants through a proof-of-concept package of interventions to a) increase intake of high quality protein and b) control enteric pathogens.

Detailed description

Stunting a major public health problem in Bangladesh, where 36% of children under the age of five are too short for their age. While dietary data indicate that protein intakes of infants and young children are largely in line with requirements, the extent to which requirements derived for healthy infants and young children are relevant in the context of frequent infections remains an important research question. Recent investigations indicate widespread pathogen carriage among Bangladeshi infants, with virtually all having at least one detectable pathogen in nondiarrheal stools by six months of age. Campylobacter and pathogenic E. Coli predominate in this setting. Enteric pathogens can compete with the host for available nutrients or alter nutrient metabolism. Acting via environmental enteric dysfunction, they can alter both digestion-through loss of digestive enzymes-and absorption of nutrients. Microbial translocation may further alter specific amino acid requirements. Even in the absence of acute diarrheal disease, enteric pathogen carriage is strongly associated with linear growth faltering. Combining the effects of high pathogen burden and poor diet, as indicated by low energy and protein from complementary foods, observational evidence suggests that the potentially preventable length-for-age Z-score deficit may be as high as 0.98. The present trial will test the combination of a) protein supplementation in the form of a protein-rich blended food or an egg, both fed daily to infants 6-12 months of age, and b) azithromycin treatment for enteric pathogens. The primary outcome will be change in length-for-age Z-score from the 6 to 12 months. Biochemical, microbiological and clinical intermediates will be measured to inform our secondary aims.

Interventions

Azithromycin oral suspension (10 mg/kg; 3 days) administered by study personnel at 6 and 9 months of age

DRUGPlacebos

Contain inert excipients only

DIETARY_SUPPLEMENTProtein Supplement

Blended food providing 125 kcal and 10 g protein as egg white powder prepared as porridge and fed daily to infants from 6-12 months of age

DIETARY_SUPPLEMENTIsocaloric Supplement

Blended food providing 125 kcal and 1 g protein as rice powder prepared as porridge and fed daily to infants from 6-12 months of age

DIETARY_SUPPLEMENTEgg

Egg provided daily to infants from 6-12 months of age

BEHAVIORALNutrition Education

Monthly messaging on infant and young child feeding

Sponsors

International Centre for Diarrhoeal Disease Research, Bangladesh
CollaboratorOTHER
Bill and Melinda Gates Foundation
CollaboratorOTHER
Johns Hopkins Bloomberg School of Public Health
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Participants, care providers, investigators and outcomes assessors will be blinded to the azithromycin or placebo interventions. Neither participants nor outcomes assessors will be masked to the nutrition interventions. Investigators will be masked to the nutrition interventions.

Intervention model description

For this 2 x 4 factorial, cluster-randomized trial, 566 previously defined clusters will be assigned independently to 8 different combinations of interventions: 1) azithromycin and protein supplementation; 2) azithromycin and isocaloric supplementation; 3) azithromycin and egg; 4) azithromycin and control (nutrition education); 5) placebo and protein supplementation; 6) placebo and isocaloric supplementation; 7) placebo and egg; 8) placebo and control (nutrition education).

Eligibility

Sex/Gender
ALL
Age
3 Months to 6 Months
Healthy volunteers
No

Inclusion criteria

* Born to women enrolled in ongoing community trial (NCT02909179) over a one-year period

Exclusion criteria

* Born to women not registered as part of the ongoing community trial (NCT02909179)

Design outcomes

Primary

MeasureTime frame
Length-for-age Z-score (LAZ) at 12 months of age12 months

Secondary

MeasureTime frameDescription
Inflammatory biomarkers6 and 12 monthsPlasma alpha-1 acid glycoprotein, C-reactive protein and interleukin-6, by ELISA; stool inflammatory cytokines, by ELISA
Bone biomarkers6 and 12 monthsPlasma collagen type X and N-Terminal Pro-C-Type Natriuretic Peptide (NT-ProCNP), by ELISA
Morbidity incidence6-12 monthsIncident diarrhea/dysentery or respiratory infection, based on weekly recalls
Nutrient biomarkers6 and 12 monthsSerum essential, conditionally essential amino acids and choline (by metabolomic analysis); retinol and tocopherols (HPLC); vitamin B12 (microbiological assay); zinc (AAS); ferritin and thyroglobulin (ELISA)
Body composition6, 9, 12, 15, and 18 monthsFat mass by bioelectrical impedence
Enteropathogen burden6, 6.5, 9, 9.5, 12, 15, and 18 monthsCampylobacter, enterotoxigenic Escherichia coli (ETEC), enteroaggregative Escherichia coli (EAEC), enteropathogenic Escherichia coli (EPEC), Shigella and Cryptosporidium, by quantitative polymerase chain reaction (qPCR)
Gut microbiota composition6, 6.5, 9, 9.5, 12, 15, and 18 monthsMicrobial diversity and abundance, by 16S ribosomal RNA sequencing
Environmental enteric dysfunction biomarkers6 and 12 monthsStool myeloperoxidase and intestinal fatty acid-binding protein concentrations and plasma Endogenous endotoxin-core antibody (EndoCAb), by ELISA
Antibiotic resistance6, 9, 12, 15, and 18 monthsResistance of commensal E. coli (stool) or S. pneumoniae (nasopharyngeal swab) to panel of antibiotics, by culture
Growth hormone and stress axes biomarkers6 and 12 monthsSerum insulin-like growth factor 1 (IGF-1), IGF binding protein 3, cortisol, by ELISA

Countries

Bangladesh

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 7, 2026