Protein Plus: Improving Infant Growth Through Diet and Enteric Health

NCT03683667 | Completed Phase 2 DMC

• 2 other identifiers: 00008000OPP1163259
• Study Type: interventional
• Target: 5,283
• Locations: 1 country
• Sites: 1

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.

Conditions

Stunting; Malnutrition; Protein; Enteric Pathogens; Campylobacter Infections

Keywords

linear growth; infant feeding; environmental enteric dysfunction

Outcome Measures

Primary Outcomes (1)

• Length-for-age Z-score (LAZ) at 12 months of age

  12 months

Secondary Outcomes (10)

• Nutrient biomarkers

  6 and 12 months

• Growth hormone and stress axes biomarkers

  6 and 12 months

• Enteropathogen burden

  6, 6.5, 9, 9.5, 12, 15, and 18 months

• Gut microbiota composition

  6, 6.5, 9, 9.5, 12, 15, and 18 months

• Environmental enteric dysfunction biomarkers

  6 and 12 months

Study Arms (8)

Placebo & Control

PLACEBO COMPARATOR

Placebo / Nutrition education

Drug: Placebos; Behavioral: Nutrition Education

Placebo & Protein Supplement

EXPERIMENTAL

Placebo / Protein-rich blended food / Nutrition education

Drug: Placebos; Dietary Supplement: Protein Supplement; Behavioral: Nutrition Education

Placebo & Isocaloric Supplement

PLACEBO COMPARATOR

Placebo / Isocaloric blended food / Nutrition education

Drug: Placebos; Dietary Supplement: Isocaloric Supplement; Behavioral: Nutrition Education

Placebo & Egg

EXPERIMENTAL

Placebo / Egg / Nutrition education

Drug: Placebos; Dietary Supplement: Egg; Behavioral: Nutrition Education

Azithromycin & Control

EXPERIMENTAL

Azithromycin / Nutrition education

Drug: Azithromycin Oral Product; Behavioral: Nutrition Education

Azithromycin & Protein Supplement

EXPERIMENTAL

Azithromycin / Protein-rich blended food / Nutrition education

Drug: Azithromycin Oral Product; Dietary Supplement: Protein Supplement; Behavioral: Nutrition Education

Azithromycin & Isocaloric Supplement

EXPERIMENTAL

Azithromycin Isocaloric blended food Nutrition education

Drug: Azithromycin Oral Product; Dietary Supplement: Isocaloric Supplement; Behavioral: Nutrition Education

Azithromycin and Egg

EXPERIMENTAL

Azithromycin Egg Nutrition education

Drug: Azithromycin Oral Product; Dietary Supplement: Egg; Behavioral: Nutrition Education

Interventions

Azithromycin Oral Product DRUG

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

Also known as: Azithrocin

Azithromycin & Control; Azithromycin & Isocaloric Supplement; Azithromycin & Protein Supplement; Azithromycin and Egg

Placebos DRUG

Contain inert excipients only

Placebo & Control; Placebo & Egg; Placebo & Isocaloric Supplement; Placebo & Protein Supplement

Protein Supplement DIETARY_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

Azithromycin & Protein Supplement; Placebo & Protein Supplement

Isocaloric Supplement DIETARY_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

Azithromycin & Isocaloric Supplement; Placebo & Isocaloric Supplement

Egg DIETARY_SUPPLEMENT

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

Azithromycin and Egg; Placebo & Egg

Nutrition Education BEHAVIORAL

Monthly messaging on infant and young child feeding

Azithromycin & Control; Azithromycin & Isocaloric Supplement; Azithromycin & Protein Supplement; Azithromycin and Egg; Placebo & Control; Placebo & Egg; Placebo & Isocaloric Supplement; Placebo & Protein Supplement

Eligibility Criteria

• Age: 3 Months - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

JiVitA Maternal and Child & Nutrition Research Site

Gaibandha, Bangladesh

Location

Related Publications (7)

• 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.

  PMID: 28202639 BACKGROUND

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

  PMID: 23964397 BACKGROUND

• 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.

  PMID: 26031686 BACKGROUND

• 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.

  PMID: 29333282 BACKGROUND

• Palmer AC, Hossain MI, Ali H, Ayesha K, Shaikh S, Islam MT, Johura FT, Pasqualino MM, Rahman H, Haque R, Alland K, Wu LS, Schulze KJ, Chakraborty S, West KP Jr, Alam M, Ahmed T, Labrique AB. Protein supplementation delivered alone or in combination with presumptive azithromycin treatment for enteric pathogens did not improve linear growth in Bangladeshi infants: results of a cluster-randomized controlled trial. Am J Clin Nutr. 2025 Mar;121(3):597-609. doi: 10.1016/j.ajcnut.2024.12.027. Epub 2025 Jan 7.

  PMID: 39788294 DERIVED

• Pasqualino MM, Shaikh S, Hossain MI, Islam MT, Ali H, Haque R, Ayesha K, Wu LS, Dyer B, Hasan K, Alland K, Schulze KJ, Johura FT, Alam M, West KP Jr, Ahmed T, Labrique AB, Palmer AC. An Egg Intervention Improves Ponderal But Not Linear Growth Among Infants 6-12 mo of Age in Rural Bangladesh. J Nutr. 2024 Jul;154(7):2290-2299. doi: 10.1016/j.tjnut.2024.05.006. Epub 2024 May 15.

  PMID: 38759886 DERIVED

• Tong H, Thorne-Lyman A, Palmer AC, Shaikh S, Ali H, Gao Y, Pasqualino MM, Wu L, Alland K, Schulze K, West KP Jr, Hossain MI, Labrique AB. Prelacteal feeding is not associated with infant size at 3 months in rural Bangladesh: a prospective cohort study. Int Breastfeed J. 2024 Feb 27;19(1):15. doi: 10.1186/s13006-024-00621-4.

  PMID: 38413997 DERIVED

MeSH Terms

Conditions

Growth Disorders; Kwashiorkor; Campylobacter Infections

Interventions

Eggs; Nutrition Assessment

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Severe Acute Malnutrition; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health

Study Officials

• Amanda C Palmer, PhD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

• Md Iqbal Hossain, PhD

  International Centre for Diarrhoel Disease Research, Bangladesh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: September 21, 2018
• First Posted: September 25, 2018
• Study Start: September 23, 2018
• Primary Completion: March 19, 2020
• Study Completion: March 24, 2020
• Last Updated: December 5, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)