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

NCT ID: NCT00470158

Last Updated: 2018-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2008-02-29

Brief 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.

Conditions

Anemia; Diarrhea; Iron

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

combined iron and zinc

Iron and zinc together

Group Type: EXPERIMENTAL

iron and zinc combined

Intervention Type: DIETARY_SUPPLEMENT

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.

Separate iron and zinc

Iron and zinc on separate days

Group Type: EXPERIMENTAL

iron and zinc on separate days

Intervention Type: DIETARY_SUPPLEMENT

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.

iron alone

Iron

Group Type: EXPERIMENTAL

iron

Intervention Type: DIETARY_SUPPLEMENT

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.

zinc alone

Zinc

Group Type: EXPERIMENTAL

Zinc

Intervention Type: DIETARY_SUPPLEMENT

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DIETARY_SUPPLEMENT

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Tablets were manufactured by Nutriset; S.A.S. (Malaunay, France).; Tablets were manufactured by Nutriset; S.A.S. (Malaunay, France).

Eligibility 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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 18 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role: collaborator

United States Agency for International Development (USAID)

FED

Sponsor Role: collaborator

Agency for Healthcare Research and Quality (AHRQ)

FED

Sponsor Role: collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert E Black, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Bloomberg School of Public Health

Locations

ICDDR,B

Dhaka, Mohakhali, Bangladesh

Countries

Bangladesh

References

Chang S, El Arifeen S, Bari S, Wahed MA, Rahman KM, Rahman MT, Mahmud AB, Begum N, Zaman K, Baqui AH, Black RE. Supplementing iron and zinc: double blind, randomized evaluation of separate or combined delivery. Eur J Clin Nutr. 2010 Feb;64(2):153-60. doi: 10.1038/ejcn.2009.127. Epub 2009 Nov 11.

Reference Type: RESULT

PMID: 19904293 (View on PubMed)

Other Identifiers

GHS-A-00-03-00019-00-90027844

Identifier Type: -

Identifier Source: secondary_id

H.22.05.03.11.C2

Identifier Type: -

Identifier Source: org_study_id