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| Name | Class |
|---|---|
| International Centre for Diarrhoeal Disease Research, Bangladesh | OTHER |
| Johns Hopkins Bloomberg School of Public Health | OTHER |
| University of Colorado, Denver | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1. Standard MNP | Experimental |
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| 2. High zinc, low iron MNP | Experimental |
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| 3. High zinc, low/no iron | Experimental |
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| 4. Dispersible zinc supplement | Active Comparator |
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| 5. Intermittent zinc supplement | Experimental |
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| 6. Placebo powder | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard MNP | Dietary Supplement | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Change in wasting prevalence |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert Black, MD, MPH | Johns Hopkins Bloomberg School of Public Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icddr,B | Dhaka | Bangladesh |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35015856 | Derived | 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. |
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| High zinc, low iron MNP | Dietary Supplement | 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. |
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| High zinc, low/no iron on alternating days | Dietary Supplement | 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. |
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| Dispersible zinc supplement | Dietary Supplement | 10 mg zinc in a dispersible tablet. Daily supplementation for 24 weeks. |
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| Intermittent zinc supplement | Dietary Supplement | 10 mg zinc in a dispersible tablet. Daily supplementation for 14 days at baseline and 3 months, placebo tablet on all other days. |
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| Placebo powder | Dietary Supplement | Daily provision of a placebo powder for 24 weeks. |
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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 |
| 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 |
| Incidence of diarrhea with dehydration | Incidence of diarrhea with dehydration over the 24-week follow-up period | Measured twice weekly for 24 weeks |
| Incidence of hospitalizations | Hospitalization is defined as an overnight stay in the hospital due to illness | Assessed twice weekly for 24 weeks |
| 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 |
| 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 |
| 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. |
| 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 |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| ID | Term |
|---|---|
| D003967 | Diarrhea |
| D006130 | Growth Disorders |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010335 | Pathologic Processes |
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