Delivery of Iron and Zinc Supplements: Evaluation of Interaction Effect on Biochemical and Clinical Outcomes
Condition: Anemia; Diarrhea; Iron
MeSH terms: Diarrhea
Study type: Interventional
Phase: Phase 4

Summary: 
      With the long-term public health goal of developing an effective micronutrient
      supplementation program to improve child health by improving iron and zinc status and
      decreasing morbidity due to diarrhea in areas with high rates of childhood malnutrition, we
      seek to determine the most efficacious method of decreasing childhood morbidity and mortality
      due to diarrhea in toddlers by re-examining the issue of iron and zinc interaction and
      determining if this interaction can be minimized by separate administration of iron and zinc
      supplementation.
    

Detailed description: 
      Iron supplementation is used in reducing anemia and improving hemoglobin status. Zinc
      supplementation is emerging as possibly an efficacious preventive measure in decreasing
      incidence of severe diarrhea. Previous studies have suggested interactions of zinc and iron
      when given together, reducing the effects of supplementation with both minerals. One study in
      Peru has shown a decrease in interaction effect with separate supplementation of iron and
      zinc in time when compared to iron administration alone or placebo; however, an evaluation of
      clinical outcomes and zinc or iron status when iron and zinc are administered separately
      compared to supplementation of zinc and iron together or each alone has not previously been
      done. This trial will assess the effect of iron and zinc supplementation given on alternate
      days compared with giving them together in a combined supplement.

      We propose a randomized, double blind, placebo-controlled community trial of children 6-23
      months in Mirzapur, Bangladesh. We will recruit and enroll 1000 children 6-23 months old who
      are permanent residents of the selected villages. Each child will be randomly assigned to 1)
      daily alternating zinc and placebo 2) daily alternating iron/folic acid and placebo 3) daily
      alternating zinc/iron/folic acid and placebo 4) daily alternating zinc and iron/folic acid 5)
      daily placebo. Primary outcomes will include incidence of severe diarrhea, evaluated weekly
      for 6 months, hemoglobin, prevalence of anemia, and serum zinc.

      Analysis of the data will be done to compare the effect of separate iron and zinc
      supplementation as compared to combined iron and zinc supplementation as well as compared to
      iron, zinc, or placebo single supplementation. We will evaluate the difference in incidence
      rate of severe diarrhea, serum hemoglobin, percent anemia, and serum zinc. Since this will be
      a randomized, double-blind, placebo controlled trial, differences in effect will be most
      likely explained by the timing of supplement doses. If there is an improvement in clinical
      and biochemical outcomes, this would be consistent with a decreased interaction of
      absorption. If no difference is found, there may be another mechanism for the seeming
      interaction of iron and zinc besides that of mutually inhibitory absorption in the intestine.
    

Intervention name(s): iron and zinc combined; iron and zinc on separate days; iron; Zinc; placebo
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Children >= 12 months received an average of 5mg zinc/day, 6.25 Iron/day, and 25IU folic acid/day. children<12 received half that dose. This dose was alternated daily with placebo. Dissolvable doses were distributed in blister packs and reconstituted with a teaspoon of water. Doses were administered in the morning. For missed doses, the mother gave the child the next morning dose, and a second dose in the evening.; Children >= 12 months received an average of 5mg zinc/day, alternating daily with 6.25 Iron/day, and 25IU folic acid/day. Children<12 received half that dose. Dissolvable doses were distributed in blister packs and reconstituted with a teaspoon of water. Doses were administered in the morning. For missed doses, the mother gave the child the next morning dose, and a second dose in the evening.; Children >= 12 months received an average 6.25 Iron/day, and 25IU folic acid/day. Children<12 received half that dose. This dose was alternated daily with placebo. Dissolvable doses were distributed in blister packs and reconstituted with a teaspoon of water. Doses were administered in the morning. For missed doses, the mother gave the child the next morning dose, and a second dose in the evening.; Children >= 12 months received an average of 5mg zinc/day. Children<12 received half that dose. This dose was alternated daily with placebo. Dissolvable doses were distributed in blister packs and reconstituted with a teaspoon of water. Doses were administered in the morning. For missed doses, the mother gave the child the next morning dose, and a second dose in the evening.; Children received daily placebo. Dissolvable doses were distributed in blister packs and reconstituted with a teaspoon of water. Doses were administered in the morning. For missed doses, the mother gave the child the next morning dose, and a second dose in the evening.
Other intervention name(s): Tablets were manufactured by Nutriset; S.A.S. (Malaunay, France).; Tablets were manufactured by Nutriset; S.A.S. (Malaunay, France).
Intervention MeSH terms: Iron; Zinc
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: zinc; iron; interaction; diarrhea; delivery