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

Diarrhea Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03406793
• Other study ID #: 1.05
• Status: Completed
• Phase: N/A
• Start date: February 20, 2018
• Est. completion date: January 12, 2020

Study information

• Verified date: October 2020
• Source: UCSF Benioff Children's Hospital Oakland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2886
• Est. completion date: January 12, 2020
• Est. primary completion date: January 12, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 9 Months to 11 Months

Eligibility

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

Related Conditions & MeSH terms

• Diarrhea
• Growth Disorders
• Stunting

Intervention

Dietary Supplement:
• Standard MNP
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.
• High zinc, low iron MNP
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.
• High zinc, low/no iron on alternating days
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.
• Dispersible zinc supplement
10 mg zinc in a dispersible tablet. Daily supplementation for 24 weeks.
• Intermittent zinc supplement
10 mg zinc in a dispersible tablet. Daily supplementation for 14 days at baseline and 3 months, placebo tablet on all other days.
• Placebo powder
Daily provision of a placebo powder for 24 weeks.

Locations

Country	Name	City	State
Bangladesh	Icddr,B	Dhaka

Sponsors (4)

Lead Sponsor	Collaborator
UCSF Benioff Children's Hospital Oakland	International Centre for Diarrhoeal Disease Research, Bangladesh, Johns Hopkins Bloomberg School of Public Health, University of Colorado, Denver

Country where clinical trial is conducted

Bangladesh, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of diarrhea	Incidence of diarrhea is defined as the number of diarrheal episodes per person-weeks of follow-up	Incidence over the 24-week follow-up period
Primary	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	Measured at enrollment and the end of the 24-week follow-up period
Secondary	Change in stunting prevalence	Change in the prevalence of stunting (LAZ <-2) in the study population over the 24-week follow-up period	Measured at enrollment and the end of the 24-week follow-up period
Secondary	Change in wasting prevalence	Change in the prevalence of wasting (WLZ <-2) in the study population over the 24-week follow-up period	Measured at enrollment and at the end of the 24-week follow-up period
Secondary	Incidence of dysentery	Dysentery is defined as any diarrheal episode in which the loose or watery stools contain visible red blood	Measured twice weekly for 24 weeks
Secondary	Incidence of diarrhea with dehydration	Incidence of diarrhea with dehydration over the 24-week follow-up period	Measured twice weekly for 24 weeks
Secondary	Incidence of hospitalizations	Hospitalization is defined as an overnight stay in the hospital due to illness	Assessed twice weekly for 24 weeks
Secondary	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	Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
Secondary	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	Measured at enrollment and at the end of the 24-week follow-up period in subgroup of participants in all 6 intervention groups
Secondary	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	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.
Secondary	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.	Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
Secondary	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.	Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.