Protein Plus: Improving Infant Growth Through Diet and Enteric Health
- Conditions
- Malnutrition; ProteinEnteric PathogensStuntingCampylobacter Infections
- Interventions
- Drug: PlacebosBehavioral: Nutrition EducationDietary Supplement: EggDietary Supplement: Isocaloric SupplementDietary Supplement: Protein Supplement
- Registration Number
- NCT03683667
- Lead Sponsor
- Johns Hopkins Bloomberg School of Public Health
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 5283
- Born to women enrolled in ongoing community trial (NCT02909179) over a one-year period
- Born to women not registered as part of the ongoing community trial (NCT02909179)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Azithromycin & Control Azithromycin Oral Product Azithromycin / Nutrition education Azithromycin & Protein Supplement Azithromycin Oral Product Azithromycin / Protein-rich blended food / Nutrition education Azithromycin and Egg Azithromycin Oral Product Azithromycin Egg Nutrition education Placebo & Isocaloric Supplement Placebos Placebo / Isocaloric blended food / Nutrition education Placebo & Control Nutrition Education Placebo / Nutrition education Placebo & Control Placebos Placebo / Nutrition education Placebo & Egg Placebos Placebo / Egg / Nutrition education Placebo & Isocaloric Supplement Nutrition Education Placebo / Isocaloric blended food / Nutrition education Placebo & Egg Egg Placebo / Egg / Nutrition education Azithromycin & Isocaloric Supplement Azithromycin Oral Product Azithromycin Isocaloric blended food Nutrition education Placebo & Egg Nutrition Education Placebo / Egg / Nutrition education Placebo & Isocaloric Supplement Isocaloric Supplement Placebo / Isocaloric blended food / Nutrition education Azithromycin & Control Nutrition Education Azithromycin / Nutrition education Placebo & Protein Supplement Placebos Placebo / Protein-rich blended food / Nutrition education Placebo & Protein Supplement Nutrition Education Placebo / Protein-rich blended food / Nutrition education Azithromycin & Protein Supplement Nutrition Education Azithromycin / Protein-rich blended food / Nutrition education Azithromycin & Isocaloric Supplement Isocaloric Supplement Azithromycin Isocaloric blended food Nutrition education Azithromycin and Egg Egg Azithromycin Egg Nutrition education Azithromycin and Egg Nutrition Education Azithromycin Egg Nutrition education Placebo & Protein Supplement Protein Supplement Placebo / Protein-rich blended food / Nutrition education Azithromycin & Protein Supplement Protein Supplement Azithromycin / Protein-rich blended food / Nutrition education Azithromycin & Isocaloric Supplement Nutrition Education Azithromycin Isocaloric blended food Nutrition education
- Primary Outcome Measures
Name Time Method Length-for-age Z-score (LAZ) at 12 months of age 12 months
- Secondary Outcome Measures
Name Time Method Body composition 6, 9, 12, 15, and 18 months Fat mass by bioelectrical impedence
Bone biomarkers 6 and 12 months Plasma collagen type X and N-Terminal Pro-C-Type Natriuretic Peptide (NT-ProCNP), by ELISA
Antibiotic resistance 6, 9, 12, 15, and 18 months Resistance of commensal E. coli (stool) or S. pneumoniae (nasopharyngeal swab) to panel of antibiotics, by culture
Growth hormone and stress axes biomarkers 6 and 12 months Serum insulin-like growth factor 1 (IGF-1), IGF binding protein 3, cortisol, by ELISA
Nutrient biomarkers 6 and 12 months 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)
Gut microbiota composition 6, 6.5, 9, 9.5, 12, 15, and 18 months Microbial diversity and abundance, by 16S ribosomal RNA sequencing
Enteropathogen burden 6, 6.5, 9, 9.5, 12, 15, and 18 months Campylobacter, enterotoxigenic Escherichia coli (ETEC), enteroaggregative Escherichia coli (EAEC), enteropathogenic Escherichia coli (EPEC), Shigella and Cryptosporidium, by quantitative polymerase chain reaction (qPCR)
Inflammatory biomarkers 6 and 12 months Plasma alpha-1 acid glycoprotein, C-reactive protein and interleukin-6, by ELISA; stool inflammatory cytokines, by ELISA
Environmental enteric dysfunction biomarkers 6 and 12 months Stool myeloperoxidase and intestinal fatty acid-binding protein concentrations and plasma Endogenous endotoxin-core antibody (EndoCAb), by ELISA
Morbidity incidence 6-12 months Incident diarrhea/dysentery or respiratory infection, based on weekly recalls
Trial Locations
- Locations (1)
JiVitA Maternal and Child & Nutrition Research Site
🇧🇩Gaibandha, Bangladesh