Zinc-MNP Trial for Prevention of Diarrhea and Promotion of Linear Growth

Randomized, Double-blind, Community-based Efficacy Trial of Various Doses of Zinc in Micronutrient Powders or Tablets in Young, Bangladeshi Children

Sponsors

Lead Sponsor: UCSF Benioff Children's Hospital Oakland

Collaborator: International Centre for Diarrhoeal Disease Research, Bangladesh
Johns Hopkins Bloomberg School of Public Health
University of Colorado, Denver

Source UCSF Benioff Children's Hospital Oakland
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.

Overall Status Completed
Start Date 2018-02-20
Completion Date 2020-01-12
Primary Completion Date 2020-01-12
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Incidence of diarrhea Incidence over the 24-week follow-up period
Change in length-for-age Z score Measured at enrollment and the end of the 24-week follow-up period
Secondary Outcome
Measure Time Frame
Change in stunting prevalence Measured at enrollment and the end of the 24-week follow-up period
Change in wasting prevalence Measured at enrollment and at the end of the 24-week follow-up period
Incidence of dysentery Measured twice weekly for 24 weeks
Incidence of diarrhea with dehydration Measured twice weekly for 24 weeks
Incidence of hospitalizations Assessed twice weekly for 24 weeks
Change in mean serum zinc concentration Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
Change in the prevalence of zinc deficiency Measured at enrollment and at the end of the 24-week follow-up period in subgroup of participants in all 6 intervention groups
Change in the exchangeable zinc pool size 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.
Change in ferritin concentrations Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
Change in concentrations of soluble transferrin receptor Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
Change in gut microbiota 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.
Change in amino acid metabolites associated with gut permeability 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.
Change in lipid metabolites associated with gut permeability 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.
Change in genome wide gene expression by RNA-sequencing 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.
Change in specific gene expression by quantitative Polymerase Chain Reaction 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.
Change in cellular immune function by leukocyte profiles 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.
Change in serum cytokines 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.
Enrollment 2886
Condition
Intervention

Intervention Type: Dietary Supplement

Intervention Name: Standard MNP

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.

Arm Group Label: 1. Standard MNP

Intervention Type: Dietary Supplement

Intervention Name: High zinc, low iron MNP

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.

Arm Group Label: 2. High zinc, low iron MNP

Intervention Type: Dietary Supplement

Intervention Name: High zinc, low/no iron on alternating days

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.

Arm Group Label: 3. High zinc, low/no iron

Intervention Type: Dietary Supplement

Intervention Name: Dispersible zinc supplement

Description: 10 mg zinc in a dispersible tablet. Daily supplementation for 24 weeks.

Arm Group Label: 4. Dispersible zinc supplement

Intervention Type: Dietary Supplement

Intervention Name: Intermittent zinc supplement

Description: 10 mg zinc in a dispersible tablet. Daily supplementation for 14 days at baseline and 3 months, placebo tablet on all other days.

Arm Group Label: 5. Intermittent zinc supplement

Intervention Type: Dietary Supplement

Intervention Name: Placebo powder

Description: Daily provision of a placebo powder for 24 weeks.

Arm Group Label: 6. Placebo powder

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

Gender:

All

Minimum Age:

9 Months

Maximum Age:

11 Months

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Robert Black, MD, MPH Principal Investigator Johns Hopkins Bloomberg School of Public Health
Location
Facility: Icddr,B
Location Countries

Bangladesh

Verification Date

2020-10-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 6
Arm Group

Label: 1. Standard MNP

Type: Experimental

Label: 2. High zinc, low iron MNP

Type: Experimental

Label: 3. High zinc, low/no iron

Type: Experimental

Label: 4. Dispersible zinc supplement

Type: Active Comparator

Label: 5. Intermittent zinc supplement

Type: Experimental

Label: 6. Placebo powder

Type: Placebo Comparator

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

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