- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03406793
Zinc-MNP Trial for Prevention of Diarrhea and Promotion of Linear Growth
October 30, 2020 updated by: UCSF Benioff Children's Hospital Oakland
Randomized, Double-blind, Community-based Efficacy Trial of Various Doses of Zinc in Micronutrient Powders or Tablets in Young, Bangladeshi Children
This is a randomized, double-blind, community-based efficacy trial of different doses, forms, and frequencies of zinc supplementation for the prevention of diarrhea and promotion of linear growth among children 9-11 months of age in Dhaka, Bangladesh.
Study Overview
Status
Completed
Detailed Description
Zinc is essential to support growth in young children especially for tissues undergoing rapid cellular differentiation and turnover, such as those in the immune system and gastrointestinal tract.
Therapeutic zinc supplementation has been initiated in low-income countries as part of diarrhea treatment programs to support these needs for young children but, the effects of preventive supplemental zinc as a tablet or as a multiple micronutrient powder (MNP) on child growth and diarrheal disease are mixed and pose programmatic uncertainties.
Thus, a randomized, double-blind community-based efficacy trial of five different doses, forms, and frequencies of preventive zinc supplementation vs. a placebo was designed for a study in children aged 9-11 months in an urban community in Dhaka, Bangladesh.
The primary outcomes of this 24-week study are incidence of diarrheal disease and linear growth.
Study workers will conduct in-home morbidity checks twice weekly; anthropometry will be measured at baseline, 12 weeks and 24 weeks.
Serum zinc and other related biomarkers will be measured in a subsample along with an estimate of the exchangeable zinc pool size using stable isotope techniques in a subgroup.
Therapeutic zinc will be provided as part of diarrhea treatment, in accordance with Bangladesh's national policy.
Therefore, the proposed study will determine the additional benefit of a preventive zinc supplementation intervention.
Study Type
Interventional
Enrollment (Actual)
2886
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Dhaka, Bangladesh
- Icddr,b
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
9 months to 11 months (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 9-11 months of age
- Weight-for-length Z score >= -3 according to the 2006 World Health Organization Growth Standards
- Hemoglobin concentration > = 7.0 g/dL
Exclusion Criteria:
- Presence of severe acute malnutrition, defined as a WLZ <-3 and/or the presence of bipedal edema and/or mid-upper arm circumference <115 mm;
- Presence of severe anemia, defined as a hemoglobin concentration < 7.0 g/dL
- Congenital anomalies (e.g. cardiac defects, cleft lip or palate) or any other conditions that interfere with feeding;
- Chromosomal anomalies and other organic problems (e.g. jaundice, tuberculosis)
- Currently consuming MNPs with no intention of stopping
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 1. Standard MNP
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Standard MNP, 15 micronutrients (Vitamin A 400 µg, vitamin D 5 µg, vitamin E 5 mg, vitamin C 30 mg, thiamine 0.5 mg, riboflavin 0.5 mg, niacin 6 mg, pyridoxine 0.5 mg, vitamin B12 0.9 mg, folate 150 µg, iron 10 mg, zinc 4.1 mg, copper 0.56 mg, selenium 17.0 µg and iodine 90 µg).
Daily supplementation for 24 weeks.
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Experimental: 2. High zinc, low iron MNP
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Same as group 1, except with 10 mg zinc instead of 4.1 mg and 6 mg iron instead of 10 mg.
Daily supplementation for 24 weeks.
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Experimental: 3. High zinc, low/no iron
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Same as study group 1, except with 10 mg zinc instead of 4.1 mg, and 6 mg iron and no iron on alternating days instead of 10 mg.
Daily supplementation for 24 weeks.
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Active Comparator: 4. Dispersible zinc supplement
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10 mg zinc in a dispersible tablet.
Daily supplementation for 24 weeks.
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Experimental: 5. Intermittent zinc supplement
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10 mg zinc in a dispersible tablet.
Daily supplementation for 14 days at baseline and 3 months, placebo tablet on all other days.
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Placebo Comparator: 6. Placebo powder
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Daily provision of a placebo powder for 24 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of diarrhea
Time Frame: Incidence over the 24-week follow-up period
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Incidence of diarrhea is defined as the number of diarrheal episodes per person-weeks of follow-up
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Incidence over the 24-week follow-up period
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Change in length-for-age Z score
Time Frame: Measured at enrollment and the end of the 24-week follow-up period
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Change in length-for-age Z score from enrollment to the end of the 24-week follow-up period
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Measured at enrollment and the end of the 24-week follow-up period
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in stunting prevalence
Time Frame: Measured at enrollment and the end of the 24-week follow-up period
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Change in the prevalence of stunting (LAZ <-2) in the study population over the 24-week follow-up period
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Measured at enrollment and the end of the 24-week follow-up period
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Change in wasting prevalence
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period
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Change in the prevalence of wasting (WLZ <-2) in the study population over the 24-week follow-up period
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Measured at enrollment and at the end of the 24-week follow-up period
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Incidence of dysentery
Time Frame: Measured twice weekly for 24 weeks
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Dysentery is defined as any diarrheal episode in which the loose or watery stools contain visible red blood
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Measured twice weekly for 24 weeks
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Incidence of diarrhea with dehydration
Time Frame: Measured twice weekly for 24 weeks
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Incidence of diarrhea with dehydration over the 24-week follow-up period
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Measured twice weekly for 24 weeks
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Incidence of hospitalizations
Time Frame: Assessed twice weekly for 24 weeks
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Hospitalization is defined as an overnight stay in the hospital due to illness
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Assessed twice weekly for 24 weeks
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Change in mean serum zinc concentration
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
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Change in mean serum zinc concentration among children in the biochemistry sub-group over the 24-week follow-up period
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
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Change in the prevalence of zinc deficiency
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in subgroup of participants in all 6 intervention groups
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Change in the prevalence of zinc deficiency (serum zinc concentration <9.9 umol/L) in the biochemistry subgroup from baseline to the end of the 24-week follow-up period
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Measured at enrollment and at the end of the 24-week follow-up period in subgroup of participants in all 6 intervention groups
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Change in the exchangeable zinc pool size
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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Change in the exchangeable zinc pool size from enrollment to the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP group, dispersible zinc supplement group, and placebo group
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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Change in ferritin concentrations
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
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Change in mean concentrations of ferritin from enrollment to the end of the 24-week follow-up period among participants in the biochemistry subgroup.
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
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Change in concentrations of soluble transferrin receptor
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
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Change in mean concentrations of soluble transferrin receptor from enrollment to the end of the 24-week follow-up period among participants in the biochemistry subgroup.
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
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Change in gut microbiota
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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Change in the composition of gut microbiota from enrollment to the end of the 24-week follow-up period among a subgroup of participants randomized to the high zinc, low-iron; dispersible zinc supplement; and placebo powder groups.
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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Change in amino acid metabolites associated with gut permeability
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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To compare the change in amino acid metabolites associated with gut permeability from enrollment to the end of the 24-week follow-up period among a subgroup of participants randomized to the high zinc, low-iron MNP; dispersible zinc supplement; and placebo groups.
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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Change in lipid metabolites associated with gut permeability
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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To compare the change in lipid metabolites associated with gut permeability from enrollment to the end of the 24-week follow-up period among a subgroup of participants randomized to the high zinc, low-iron MNP; dispersible zinc supplement; and placebo groups.
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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Change in genome wide gene expression by RNA-sequencing
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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To compare the change in genome wide gene expression, measured with RNA-sequencing, from enrollment to the end of the 24-week follow-up period among a subgroup of participants randomized to the high zinc, low-iron MNP; dispersible zinc supplement; and placebo groups.
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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Change in specific gene expression by quantitative Polymerase Chain Reaction
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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To compare the change in specific gene expression, measured by quantitative Polymerase Chain Reaction, from enrollment to the end of the 24-week follow-up period among a subgroup of participants randomized to the high zinc, low-iron MNP; dispersible zinc supplement; and placebo groups.
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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Change in cellular immune function by leukocyte profiles
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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To compare the change in cellular immune function by leukocyte profiles, from enrollment to the end of the 24-week follow-up period among a subgroup of participants randomized to the high zinc, low-iron MNP; dispersible zinc supplement; and placebo groups.
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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Change in serum cytokines
Time Frame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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To compare the change in serum cytokines, measured by Luminex analysis, from enrollment to the end of the 24-week follow-up period among a subgroup of participants randomized to the high zinc, low-iron MNP; dispersible zinc supplement; and placebo groups.
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Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants randomized to the high zinc, low-iron MNP, dispersible zinc supplement, and placebo groups.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Robert Black, MD, MPH, Johns Hopkins Bloomberg School of Public Health
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 20, 2018
Primary Completion (Actual)
January 12, 2020
Study Completion (Actual)
January 12, 2020
Study Registration Dates
First Submitted
January 12, 2018
First Submitted That Met QC Criteria
January 19, 2018
First Posted (Actual)
January 23, 2018
Study Record Updates
Last Update Posted (Actual)
November 3, 2020
Last Update Submitted That Met QC Criteria
October 30, 2020
Last Verified
October 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1.05
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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