Protein Plus: Improving Infant Growth Through Diet and Enteric Health
Condition: Stunting; Malnutrition; Protein; Enteric Pathogens; Campylobacter Infections
MeSH terms: Campylobacter Infections; Malnutrition; Kwashiorkor
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): Azithromycin Oral Product; Placebos; Protein Supplement; Isocaloric Supplement; Egg; Nutrition Education
Intervention type(s): Drug; Drug; Dietary Supplement; Dietary Supplement; Dietary Supplement; Behavioral
Intervention description(s): Azithromycin oral suspension (10 mg/kg; 3 days) administered by study personnel at 6 and 9 months of age; Contain inert excipients only; 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; 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 provided daily to infants from 6-12 months of age; Monthly messaging on infant and young child feeding
Other intervention name(s): Azithrocin
Intervention MeSH terms: Azithromycin
Allocation: Randomized
Intervention model: Factorial Assignment
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).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: linear growth; infant feeding; environmental enteric dysfunction