Zinc-MNP Trial for Prevention of Diarrhea and Promotion of Linear Growth
Primary Purpose
Diarrhea, Stunting
Status
Completed
Phase
Not Applicable
Locations
Bangladesh
Study Type
Interventional
Intervention
Standard MNP
High zinc, low iron MNP
High zinc, low/no iron on alternating days
Dispersible zinc supplement
Intermittent zinc supplement
Placebo powder
Sponsored by
About this trial
This is an interventional prevention trial for Diarrhea focused on measuring Zinc, Multiple micronutrient powders, Diarrhea, Stunting
Eligibility Criteria
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
Sites / Locations
- Icddr,B
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Experimental
Placebo Comparator
Arm Label
1. Standard MNP
2. High zinc, low iron MNP
3. High zinc, low/no iron
4. Dispersible zinc supplement
5. Intermittent zinc supplement
6. Placebo powder
Arm Description
Outcomes
Primary Outcome Measures
Incidence of diarrhea
Incidence of diarrhea is defined as the number of diarrheal episodes per person-weeks of follow-up
Change in length-for-age Z score
Change in length-for-age Z score from enrollment to the end of the 24-week follow-up period
Secondary Outcome Measures
Change in stunting prevalence
Change in the prevalence of stunting (LAZ <-2) in the study population over the 24-week follow-up period
Change in wasting prevalence
Change in the prevalence of wasting (WLZ <-2) in the study population over the 24-week follow-up period
Incidence of dysentery
Dysentery is defined as any diarrheal episode in which the loose or watery stools contain visible red blood
Incidence of diarrhea with dehydration
Incidence of diarrhea with dehydration over the 24-week follow-up period
Incidence of hospitalizations
Hospitalization is defined as an overnight stay in the hospital due to illness
Change in mean serum zinc concentration
Change in mean serum zinc concentration among children in the biochemistry sub-group over the 24-week follow-up period
Change in the prevalence of zinc deficiency
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
Change in the exchangeable zinc pool size
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
Change in ferritin concentrations
Change in mean concentrations of ferritin from enrollment to the end of the 24-week follow-up period among participants in the biochemistry subgroup.
Change in concentrations of soluble transferrin receptor
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.
Change in gut microbiota
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.
Change in amino acid metabolites associated with gut permeability
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.
Change in lipid metabolites associated with gut permeability
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.
Change in genome wide gene expression by RNA-sequencing
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.
Change in specific gene expression by quantitative Polymerase Chain Reaction
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.
Change in cellular immune function by leukocyte profiles
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.
Change in serum cytokines
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.
Full Information
NCT ID
NCT03406793
First Posted
January 12, 2018
Last Updated
October 30, 2020
Sponsor
UCSF Benioff Children's Hospital Oakland
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Johns Hopkins Bloomberg School of Public Health, University of Colorado, Denver
1. Study Identification
Unique Protocol Identification Number
NCT03406793
Brief Title
Zinc-MNP Trial for Prevention of Diarrhea and Promotion of Linear Growth
Official Title
Randomized, Double-blind, Community-based Efficacy Trial of Various Doses of Zinc in Micronutrient Powders or Tablets in Young, Bangladeshi Children
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
February 20, 2018 (Actual)
Primary Completion Date
January 12, 2020 (Actual)
Study Completion Date
January 12, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UCSF Benioff Children's Hospital Oakland
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Johns Hopkins Bloomberg School of Public Health, University of Colorado, Denver
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diarrhea, Stunting
Keywords
Zinc, Multiple micronutrient powders, Diarrhea, Stunting
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2886 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1. Standard MNP
Arm Type
Experimental
Arm Title
2. High zinc, low iron MNP
Arm Type
Experimental
Arm Title
3. High zinc, low/no iron
Arm Type
Experimental
Arm Title
4. Dispersible zinc supplement
Arm Type
Active Comparator
Arm Title
5. Intermittent zinc supplement
Arm Type
Experimental
Arm Title
6. Placebo powder
Arm Type
Placebo Comparator
Intervention Type
Dietary Supplement
Intervention Name(s)
Standard MNP
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
High zinc, low iron MNP
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
High zinc, low/no iron on alternating days
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Dispersible zinc supplement
Intervention Description
10 mg zinc in a dispersible tablet. Daily supplementation for 24 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
Intermittent zinc supplement
Intervention Description
10 mg zinc in a dispersible tablet. Daily supplementation for 14 days at baseline and 3 months, placebo tablet on all other days.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo powder
Intervention Description
Daily provision of a placebo powder for 24 weeks.
Primary Outcome Measure Information:
Title
Incidence of diarrhea
Description
Incidence of diarrhea is defined as the number of diarrheal episodes per person-weeks of follow-up
Time Frame
Incidence over the 24-week follow-up period
Title
Change in length-for-age Z score
Description
Change in length-for-age Z score from enrollment to the end of the 24-week follow-up period
Time Frame
Measured at enrollment and the end of the 24-week follow-up period
Secondary Outcome Measure Information:
Title
Change in stunting prevalence
Description
Change in the prevalence of stunting (LAZ <-2) in the study population over the 24-week follow-up period
Time Frame
Measured at enrollment and the end of the 24-week follow-up period
Title
Change in wasting prevalence
Description
Change in the prevalence of wasting (WLZ <-2) in the study population over the 24-week follow-up period
Time Frame
Measured at enrollment and at the end of the 24-week follow-up period
Title
Incidence of dysentery
Description
Dysentery is defined as any diarrheal episode in which the loose or watery stools contain visible red blood
Time Frame
Measured twice weekly for 24 weeks
Title
Incidence of diarrhea with dehydration
Description
Incidence of diarrhea with dehydration over the 24-week follow-up period
Time Frame
Measured twice weekly for 24 weeks
Title
Incidence of hospitalizations
Description
Hospitalization is defined as an overnight stay in the hospital due to illness
Time Frame
Assessed twice weekly for 24 weeks
Title
Change in mean serum zinc concentration
Description
Change in mean serum zinc concentration among children in the biochemistry sub-group over the 24-week follow-up period
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
Title
Change in the prevalence of zinc deficiency
Description
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
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
Title
Change in the exchangeable zinc pool size
Description
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
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.
Title
Change in ferritin concentrations
Description
Change in mean concentrations of ferritin from enrollment to the end of the 24-week follow-up period among participants in the biochemistry subgroup.
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
Title
Change in concentrations of soluble transferrin receptor
Description
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.
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
Title
Change in gut microbiota
Description
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.
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.
Title
Change in amino acid metabolites associated with gut permeability
Description
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.
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.
Title
Change in lipid metabolites associated with gut permeability
Description
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.
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.
Title
Change in genome wide gene expression by RNA-sequencing
Description
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.
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.
Title
Change in specific gene expression by quantitative Polymerase Chain Reaction
Description
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.
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.
Title
Change in cellular immune function by leukocyte profiles
Description
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.
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.
Title
Change in serum cytokines
Description
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.
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
9 Months
Maximum Age & Unit of Time
11 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Black, MD, MPH
Organizational Affiliation
Johns Hopkins Bloomberg School of Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icddr,B
City
Dhaka
Country
Bangladesh
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35015856
Citation
Islam MM, Black RE, Krebs NF, Westcott J, Long J, Islam KM, Peerson JM, Sthity RA, Khandaker AM, Hasan M, El Arifeen S, Ahmed T, King JC, McDonald CM. Different Doses, Forms, and Frequencies of Zinc Supplementation for the Prevention of Diarrhea and Promotion of Linear Growth among Young Bangladeshi Children: A Six-Arm, Randomized, Community-Based Efficacy Trial. J Nutr. 2022 May 5;152(5):1306-1315. doi: 10.1093/jn/nxab439.
Results Reference
derived
Learn more about this trial
Zinc-MNP Trial for Prevention of Diarrhea and Promotion of Linear Growth
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