Clinical trial NCT03406793: 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
Overall status: COMPLETED
Phase: NA
Conditions: Diarrhea
Stunting
Keywords: Zinc
Multiple micronutrient powders
Diarrhea
Stunting
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Johns Hopkins Bloomberg School of Public Health
name: University of Colorado, Denver
First posted: 2018-01-23
Enrollment: 2886
Sex: ALL
Minimum age (years): 9
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Incidence of diarrhea
timeFrame: Incidence over the 24-week follow-up period
measure: Change in length-for-age Z score
timeFrame: Measured at enrollment and the end of the 24-week follow-up period
Secondary outcomes:
measure: Change in stunting prevalence
timeFrame: Measured at enrollment and the end of the 24-week follow-up period
measure: Change in wasting prevalence
timeFrame: Measured at enrollment and at the end of the 24-week follow-up period
measure: Incidence of dysentery
timeFrame: Measured twice weekly for 24 weeks
measure: Incidence of diarrhea with dehydration
timeFrame: Measured twice weekly for 24 weeks
measure: Incidence of hospitalizations
timeFrame: Assessed twice weekly for 24 weeks
measure: Change in mean serum zinc concentration
timeFrame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
measure: Change in the prevalence of zinc deficiency
timeFrame: Measured at enrollment and at the end of the 24-week follow-up period in subgroup of participants in all 6 intervention groups
measure: Change in the exchangeable zinc pool size
timeFrame: 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.
measure: Change in ferritin concentrations
timeFrame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
measure: Change in concentrations of soluble transferrin receptor
timeFrame: Measured at enrollment and at the end of the 24-week follow-up period in a subgroup of participants in all 6 intervention groups
measure: Change in gut microbiota
timeFrame: 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.
measure: Change in amino acid metabolites associated with gut permeability
timeFrame: 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.
measure: Change in lipid metabolites associated with gut permeability
timeFrame: 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.
measure: Change in genome wide gene expression by RNA-sequencing
timeFrame: 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.
measure: Change in specific gene expression by quantitative Polymerase Chain Reaction
timeFrame: 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.
measure: Change in cellular immune function by leukocyte profiles
timeFrame: 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.
measure: Change in serum cytokines
timeFrame: 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.
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Icddr,B
Study officials:
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Robert Black, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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.