Protein Plus: Improving Infant Growth Through Diet and Enteric Health

NCT ID: NCT03683667

Last Updated: 2022-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

5283 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-23

Study Completion Date

2020-03-24

Brief Summary

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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

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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.

Conditions

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Stunting Malnutrition; Protein Enteric Pathogens Campylobacter Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

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).
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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Placebo & Control

Placebo / Nutrition education

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

Contain inert excipients only

Nutrition Education

Intervention Type BEHAVIORAL

Monthly messaging on infant and young child feeding

Placebo & Protein Supplement

Placebo / Protein-rich blended food / Nutrition education

Group Type EXPERIMENTAL

Placebos

Intervention Type DRUG

Contain inert excipients only

Protein Supplement

Intervention Type 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

Nutrition Education

Intervention Type BEHAVIORAL

Monthly messaging on infant and young child feeding

Placebo & Isocaloric Supplement

Placebo / Isocaloric blended food / Nutrition education

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

Contain inert excipients only

Isocaloric Supplement

Intervention Type 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

Nutrition Education

Intervention Type BEHAVIORAL

Monthly messaging on infant and young child feeding

Placebo & Egg

Placebo / Egg / Nutrition education

Group Type EXPERIMENTAL

Placebos

Intervention Type DRUG

Contain inert excipients only

Egg

Intervention Type DIETARY_SUPPLEMENT

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

Nutrition Education

Intervention Type BEHAVIORAL

Monthly messaging on infant and young child feeding

Azithromycin & Control

Azithromycin / Nutrition education

Group Type EXPERIMENTAL

Azithromycin Oral Product

Intervention Type DRUG

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

Nutrition Education

Intervention Type BEHAVIORAL

Monthly messaging on infant and young child feeding

Azithromycin & Protein Supplement

Azithromycin / Protein-rich blended food / Nutrition education

Group Type EXPERIMENTAL

Azithromycin Oral Product

Intervention Type DRUG

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

Protein Supplement

Intervention Type 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

Nutrition Education

Intervention Type BEHAVIORAL

Monthly messaging on infant and young child feeding

Azithromycin & Isocaloric Supplement

Azithromycin Isocaloric blended food Nutrition education

Group Type EXPERIMENTAL

Azithromycin Oral Product

Intervention Type DRUG

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

Isocaloric Supplement

Intervention Type 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

Nutrition Education

Intervention Type BEHAVIORAL

Monthly messaging on infant and young child feeding

Azithromycin and Egg

Azithromycin Egg Nutrition education

Group Type EXPERIMENTAL

Azithromycin Oral Product

Intervention Type DRUG

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

Egg

Intervention Type DIETARY_SUPPLEMENT

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

Nutrition Education

Intervention Type BEHAVIORAL

Monthly messaging on infant and young child feeding

Interventions

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Azithromycin Oral Product

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

Intervention Type DRUG

Placebos

Contain inert excipients only

Intervention Type DRUG

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

Intervention Type DIETARY_SUPPLEMENT

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

Intervention Type DIETARY_SUPPLEMENT

Egg

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

Intervention Type DIETARY_SUPPLEMENT

Nutrition Education

Monthly messaging on infant and young child feeding

Intervention Type BEHAVIORAL

Other Intervention Names

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Azithrocin

Eligibility Criteria

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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)
Minimum Eligible Age

3 Months

Maximum Eligible Age

6 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role collaborator

Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amanda C Palmer, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Bloomberg School of Public Health

Md Iqbal Hossain, PhD

Role: PRINCIPAL_INVESTIGATOR

International Centre for Diarrhoel Disease Research, Bangladesh

Locations

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JiVitA Maternal and Child & Nutrition Research Site

Gaibandha, , Bangladesh

Site Status

Countries

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Bangladesh

References

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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.

Reference Type BACKGROUND
PMID: 28202639 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 23964397 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26031686 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29333282 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39788294 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38759886 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38413997 (View on PubMed)

Other Identifiers

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OPP1163259

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

00008000

Identifier Type: -

Identifier Source: org_study_id

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