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

Study Description

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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.

Condition or disease	Intervention/treatment	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

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.

Study Design

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	1000 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	Delivery of Iron and Zinc Supplements: Evaluation of Interaction Effect on Biochemical and Clinical Outcomes
Study Start Date :	May 2007
Actual Primary Completion Date :	February 2008
Actual Study Completion Date :	February 2008

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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.

Outcome Measures

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Primary Outcome Measures :

1. Incidence of Diarrhea [ Time Frame: 6 months ]
   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 :

1. Change in Hemoglobin [ Time Frame: 6 months ]
2. Change in Zinc Status [ Time Frame: 6 months ]
3. Percent Anemic [ Time Frame: 6 months ]

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	6 Months to 18 Months (Child)
Sexes Eligible for Study:	All
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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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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)

Agency for Healthcare Research and Quality (AHRQ)

Investigators

Principal Investigator:	Robert E Black, MD, MPH	Johns Hopkins Bloomberg School of Public Health

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

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.

Responsible Party:	Johns Hopkins Bloomberg 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
First Posted:	May 7, 2007
Results First Posted:	September 19, 2011
Last Update Posted:	April 20, 2018
Last Verified:	December 2009

Keywords provided by Johns Hopkins Bloomberg School of Public Health:

zinc; iron; interaction; diarrhea; delivery

Additional relevant MeSH terms:

Diarrhea; Signs and Symptoms, Digestive; Signs and Symptoms; Iron; Zinc	Trace Elements; Micronutrients; Growth Substances; Physiological Effects of Drugs