AnemiaPhase 4NCT00470158
Delivery of Iron and Zinc Supplements: Evaluation of Interaction Effect on Biochemical and Clinical Outcomes
A Phase 4 study testing iron and zinc combined, iron and zinc on separate days and iron in people with Anemia and Diarrhea, run by Johns Hopkins Bloomberg School of Public Health at 1 site in Bangladesh.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 to 18 monthsHealthy volunteers can take part
- What is being tested?
- iron and zinc combined, iron and zinc on separate days and iron
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,000 participants
- Where
- 1 siteBangladesh
- Study dates
- May 2007to Feb 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Children 6-18 months old
- Permanent residents of the selected villages
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Being tested
- iron and zinc combined, iron and zinc on separate days, iron, Zinc, placebo
- Keywords
- zinc, iron, interaction, diarrhea, delivery
- Medical subject headings
- Anemia, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iron and zinc combinedDietary supplement
Also called Tablets were manufactured by Nutriset, S.A.S. (Malaunay, France).
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.
iron and zinc on separate daysDietary supplement
Also called Tablets were manufactured by Nutriset, S.A.S. (Malaunay, France).
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.
ironDietary 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.
ZincDietary 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.
placeboDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| combined iron and zinc | Experimental | Iron and zinc together Receives: Dietary Supplement: iron and zinc combined |
| Separate iron and zinc | Experimental | Iron and zinc on separate days Receives: Dietary Supplement: iron and zinc on separate days |
| iron alone | Experimental | Iron Receives: Dietary Supplement: iron |
| zinc alone | Experimental | Zinc Receives: Dietary Supplement: Zinc |
| placebo | Placebo comparator | Not described Receives: Dietary Supplement: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Diarrhea
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.
Measured: 6 months
Secondary outcomes (3)
Change in Hemoglobin
Measured: 6 months
Change in Zinc Status
Measured: 6 months
Percent Anemic
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2007 (estimated)
- Study startMay 2007
- Primary completionFeb 2008
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AnemiaStudies of the same condition, open and under way.
- More trials run by Johns Hopkins Bloomberg School of Public HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins Bloomberg School of Public Health
- Sponsor type
- University, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh, United States Agency for International Development (USAID), Agency for Healthcare Research and Quality (AHRQ)
- Responsible party
- Sponsor
- Investigators
- Robert E Black, MD, MPH, Principal investigator, Johns Hopkins Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00470158
- Sponsor's protocol ID
- H.22.05.03.11.C2
- Other IDs
- GHS-A-00-03-00019-00-90027844
- Status last verified
- Dec 2009
- First submitted
- 3 May 2007
- Last updated
- 20 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 19904293
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Delivery of Iron and Zinc Supplements: Evaluation of Interaction Effect on Biochemical and Clinical Outcomes
- ClinicalTrials.gov ID
- NCT00470158
- Acronym / sponsor ID
- H.22.05.03.11.C2
- Keywords
- zinc, iron, interaction, diarrhea, delivery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,000 participants (actual)
- Lead sponsor
- Johns Hopkins Bloomberg School of Public HealthUniversity, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh, United States Agency for International Development (USAID), Agency for Healthcare Research and Quality (AHRQ)
- Study start
- May 2007
- Primary completion
- Feb 2008 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 7 May 2007 (estimated)
- Results
- Posted 19 Sep 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| combined iron and zinc | Experimental | Dietary Supplement: iron and zinc combinedIron and zinc together |
| Separate iron and zinc | Experimental | Dietary Supplement: iron and zinc on separate daysIron and zinc on separate days |
| iron alone | Experimental | Dietary Supplement: ironIron |
| zinc alone | Experimental | Dietary Supplement: ZincZinc |
| placebo | Placebo comparator | Dietary Supplement: placebo |
Who may qualify
- Ages
- 6 to 18 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Children 6-18 months old
- Permanent residents of the selected villages
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iron and zinc combinedAlso: Tablets were manufactured by Nutriset, S.A.S. (Malaunay, France).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. | Dietary supplement | combined iron and zinc |
| iron and zinc on separate daysAlso: Tablets were manufactured by Nutriset, S.A.S. (Malaunay, France).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. | Dietary supplement | Separate iron and zinc |
| ironChildren >= 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. | Dietary supplement | iron alone |
| ZincChildren >= 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. | Dietary supplement | zinc alone |
| placeboChildren 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. | Dietary supplement | placebo |
Primary outcome
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.
3 secondary outcomes
Change in Hemoglobin
Time frame: 6 months
Change in Zinc Status
Time frame: 6 months
Percent Anemic
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19904293Chang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert E Black, MD, MPH principal investigator
Johns Hopkins Bloomberg School of Public Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing iron and zinc combined, iron and zinc on separate days and iron in people with Anemia and Diarrhea, run by Johns Hopkins Bloomberg School of Public Health at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Diarrhea (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00470158, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2018.