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

Not Applicable

Completed

• Conditions: Diarrhea; Stunting
• Interventions: Dietary Supplement: High zinc, low/no iron on alternating days; Dietary Supplement: Standard MNP; Dietary Supplement: Dispersible zinc supplement; Dietary Supplement: Placebo powder; Dietary Supplement: High zinc, low iron MNP; Dietary Supplement: Intermittent zinc supplement

• Registration Number: NCT03406793
• Lead Sponsor: 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.

Study Timeline

• Study First Submitted: 2018-01-12
• Study First Submitted QC: 2018-01-19
• Study First Posted: 2018-01-23
• Study Start: 2018-02-20
• Primary Completion: 2020-01-12
• Study Completion: 2020-01-12
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-30
• Last Update Posted: 2020-11-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2886

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3. High zinc, low/no iron	High zinc, low/no iron on alternating days	-
1. Standard MNP	Standard MNP	-
4. Dispersible zinc supplement	Dispersible zinc supplement	-
6. Placebo powder	Placebo powder	-
2. High zinc, low iron MNP	High zinc, low iron MNP	-
5. Intermittent zinc supplement	Intermittent zinc supplement	-

Primary Outcome Measures

Name	Time	Method
Incidence of diarrhea	Incidence over the 24-week follow-up period	Incidence of diarrhea is defined as the number of diarrheal episodes per person-weeks of follow-up
Change in length-for-age Z score	Measured at enrollment and the end of the 24-week follow-up period	Change in length-for-age Z score from enrollment to the end of the 24-week follow-up period

Secondary Outcome Measures

Name	Time	Method
Change in stunting prevalence	Measured at enrollment and the end of the 24-week follow-up period	Change in the prevalence of stunting (LAZ \<-2) in the study population over the 24-week follow-up period
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 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 wasting prevalence	Measured at enrollment and at the end of the 24-week follow-up period	Change in the prevalence of wasting (WLZ \<-2) in the study population over the 24-week follow-up period
Incidence of diarrhea with dehydration	Measured twice weekly for 24 weeks	Incidence of diarrhea with dehydration over the 24-week follow-up period
Incidence of hospitalizations	Assessed twice weekly for 24 weeks	Hospitalization is defined as an overnight stay in the hospital due to illness
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 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	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 mean concentrations of ferritin from enrollment to the end of the 24-week follow-up period among participants in the biochemistry subgroup.
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.	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 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.	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.
Incidence of dysentery	Measured twice weekly for 24 weeks	Dysentery is defined as any diarrheal episode in which the loose or watery stools contain visible red blood
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 mean serum zinc concentration among children in the biochemistry sub-group over the 24-week follow-up period
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 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	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 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	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.	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 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.	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 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.	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 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.	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.

Trial Locations

Locations (1)

Icddr,B; 🇧🇩 Dhaka, Bangladesh