Protein Plus: Improving Infant Growth Through Diet and Enteric Health

Stunting Clinical Trial

— JiVitA-6  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03683667
• Other study ID #: 00008000
• Secondary ID: OPP1163259
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 23, 2018
• Est. completion date: March 24, 2020

Study information

• Verified date: December 2022
• Source: Johns Hopkins Bloomberg School of Public Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5283
• Est. completion date: March 24, 2020
• Est. primary completion date: March 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 6 Months

Eligibility

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)

Related Conditions & MeSH terms

• Campylobacter Infections
• Enteric Pathogens
• Kwashiorkor
• Malnutrition
• Malnutrition; Protein
• Stunting

Intervention

Drug:
• Azithromycin Oral Product
Azithromycin oral suspension (10 mg/kg; 3 days) administered by study personnel at 6 and 9 months of age
• Placebos
Contain inert excipients only

Dietary Supplement:
• Protein 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
• Isocaloric 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
• Egg
Egg provided daily to infants from 6-12 months of age

Behavioral:
• Nutrition Education
Monthly messaging on infant and young child feeding

Locations

Country	Name	City	State
Bangladesh	JiVitA Maternal and Child & Nutrition Research Site	Gaibandha

Sponsors (3)

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

Country where clinical trial is conducted

Bangladesh, 

References & Publications (4)

Arsenault JE, Brown KH. Dietary Protein Intake in Young Children in Selected Low-Income Countries Is Generally Adequate in Relation to Estimated Requirements for Healthy Children, Except When Complementary Food Intake Is Low. J Nutr. 2017 May;147(5):932-939. doi: 10.3945/jn.116.239657. Epub 2017 Feb 15. — View Citation

Lang D; MAL-ED Network Investigators. Opportunities to assess factors contributing to the development of the intestinal microbiota in infants living in developing countries. Microb Ecol Health Dis. 2015 May 29;26:28316. doi: 10.3402/mehd.v26.28316. eCollection 2015. — View Citation

MAL-ED Network Investigators. Relationship between growth and illness, enteropathogens and dietary intakes in the first 2 years of life: findings from the MAL-ED birth cohort study. BMJ Glob Health. 2017 Dec 28;2(4):e000370. doi: 10.1136/bmjgh-2017-000370. eCollection 2017. — View Citation

Uauy R. Keynote: rethinking protein. Food Nutr Bull. 2013 Jun;34(2):228-31. doi: 10.1177/156482651303400213. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length-for-age Z-score (LAZ) at 12 months of age		12 months
Secondary	Nutrient biomarkers	Serum essential, conditionally essential amino acids and choline (by metabolomic analysis); retinol and tocopherols (HPLC); vitamin B12 (microbiological assay); zinc (AAS); ferritin and thyroglobulin (ELISA)	6 and 12 months
Secondary	Growth hormone and stress axes biomarkers	Serum insulin-like growth factor 1 (IGF-1), IGF binding protein 3, cortisol, by ELISA	6 and 12 months
Secondary	Enteropathogen burden	Campylobacter, enterotoxigenic Escherichia coli (ETEC), enteroaggregative Escherichia coli (EAEC), enteropathogenic Escherichia coli (EPEC), Shigella and Cryptosporidium, by quantitative polymerase chain reaction (qPCR)	6, 6.5, 9, 9.5, 12, 15, and 18 months
Secondary	Gut microbiota composition	Microbial diversity and abundance, by 16S ribosomal RNA sequencing	6, 6.5, 9, 9.5, 12, 15, and 18 months
Secondary	Environmental enteric dysfunction biomarkers	Stool myeloperoxidase and intestinal fatty acid-binding protein concentrations and plasma Endogenous endotoxin-core antibody (EndoCAb), by ELISA	6 and 12 months
Secondary	Inflammatory biomarkers	Plasma alpha-1 acid glycoprotein, C-reactive protein and interleukin-6, by ELISA; stool inflammatory cytokines, by ELISA	6 and 12 months
Secondary	Bone biomarkers	Plasma collagen type X and N-Terminal Pro-C-Type Natriuretic Peptide (NT-ProCNP), by ELISA	6 and 12 months
Secondary	Morbidity incidence	Incident diarrhea/dysentery or respiratory infection, based on weekly recalls	6-12 months
Secondary	Body composition	Fat mass by bioelectrical impedence	6, 9, 12, 15, and 18 months
Secondary	Antibiotic resistance	Resistance of commensal E. coli (stool) or S. pneumoniae (nasopharyngeal swab) to panel of antibiotics, by culture	6, 9, 12, 15, and 18 months