Delivery of Iron and Zinc Supplements: Evaluation of Interaction Effect on Biochemical and Clinical Outcomes

This study has been completed.
Sponsor:
Collaborators:
International Centre for Diarrhoeal Disease Research, Bangladesh
United States Agency for International Development (USAID)
Information provided by:
Johns Hopkins Bloomberg School of Public Health
ClinicalTrials.gov Identifier:
NCT00470158
First received: May 3, 2007
Last updated: August 10, 2011
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Anemia
Diarrhea
Iron
Dietary Supplement: iron and zinc combined
Dietary Supplement: iron and zinc on separate days
Dietary Supplement: iron
Dietary Supplement: Zinc
Dietary Supplement: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Delivery of Iron and Zinc Supplements: Evaluation of Interaction Effect on Biochemical and Clinical Outcomes

Resource links provided by NLM:


Further study details as provided by Johns Hopkins Bloomberg School of Public Health:

Primary Outcome Measures:
  • Incidence of Diarrhea [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    A diarrhea episode was defined as three or more loose, liquid, or watery stools for 2 consecutive days, separated in time from an earlier or subsequent episode by at least 2 consecutive diarrhea-free days.


Secondary Outcome Measures:
  • Change in Hemoglobin [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Change in Zinc Status [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Percent Anemic [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 1000
Study Start Date: May 2007
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: combined iron and zinc
Iron and zinc together
Dietary Supplement: iron and zinc combined
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.
Other Names:
  • Tablets were manufactured by Nutriset
  • S.A.S. (Malaunay, France).
Experimental: Separate iron and zinc
Iron and zinc on separate days
Dietary Supplement: iron and zinc on separate days
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.
Other Names:
  • Tablets were manufactured by Nutriset
  • S.A.S. (Malaunay, France).
Experimental: iron alone
Iron
Dietary Supplement: iron
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.
Experimental: zinc alone
Zinc
Dietary Supplement: Zinc
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.
Placebo Comparator: placebo Dietary Supplement: placebo
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.

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.

  Eligibility

Ages Eligible for Study:   6 Months to 18 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Children 6-18 months old
  • Permanent residents of the selected villages

Exclusion Criteria:

  • Severe malnutrition requiring hospitalization (defined as weight for height <-3 SD Z-score)
  • Severe anemia requiring treatment (hemoglobin < 70 g/L)
  • Chronic illness that would impair feeding ability
  • Likely to move in next 6 months.
  • Fever greater than 38.5
  • Regular iron supplementation
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00470158

Locations
Bangladesh
ICDDR,B
Dhaka, Mohakhali, Bangladesh, 1212
Sponsors and Collaborators
Johns Hopkins Bloomberg School of Public Health
International Centre for Diarrhoeal Disease Research, Bangladesh
United States Agency for International Development (USAID)
Investigators
Principal Investigator: Robert E Black, MD, MPH Johns Hopkins Bloomberg School of Public Health
  More Information

Publications:
Responsible Party: Robert Black, Johns Hopkins School of Public Health
ClinicalTrials.gov Identifier: NCT00470158     History of Changes
Other Study ID Numbers: H.22.05.03.11.C2, GHS-A-00-03-00019-00-90027844
Study First Received: May 3, 2007
Results First Received: August 10, 2011
Last Updated: August 10, 2011
Health Authority: United States: Institutional Review Board
Bangladesh: Ethical Review Committee

Keywords provided by Johns Hopkins Bloomberg School of Public Health:
zinc
iron
interaction
diarrhea
delivery

Additional relevant MeSH terms:
Anemia
Diarrhea
Hematologic Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Zinc
Iron
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014