Study Protocol for a Randomized, Double-Blind, Community-Based Efficacy Trial of Various Doses of Zinc in Micronutrient Powders or Tablets in Young Bangladeshi Children

Abstract

Zinc is essential to supporting 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. The protocol has been approved by the Institutional Review Boards (IRBs) of icddr,b and Children’s Hospital Oakland Research Institute (CHORI). The IRB review process is underway at the University of Colorado Denver as well.

Improving nutritional status among urban poor children in sub‐Saharan Africa: An evidence‐informed Delphi‐based consultation

“…Our search also yielded three published protocol papers linked to ongoing intervention studies, one of which met our inclusion criteria. The study of Islam et al (2018) aims to evaluate the effect of various doses, forms and frequencies of preventative daily zinc supplementation over a 24‐week period on reducing diarrhoea and improving growth, specifically LAZ, in IYC aged 9–11 months in the peri‐urban low‐income area of Mirpur (Dhaka, Bangladesh) (Clinical trials.gov: NCT03406793).…”

Exchangeable Zinc Pool Size Reflects Form of Zinc Supplementation in Young Children and Is Not Associated with Markers of Inflammation

“…This was a sub-study of the randomized, partially blinded, multi-arm, placebo-controlled zinc in powders trial (ZiPT) [ 6 , 7 ]. The primary aim was to compare the change in the EZP size from baseline to endline in a subgroup of children at risk for zinc deficiency who were preventively supplemented with 10 mg of zinc as part of an MNP added to a single meal each day, as a standalone daily dispersible tablet, vs. a placebo powder for 24 weeks.…”

“…To determine the extent to which EZP responds to changes in zinc intake and reflects zinc status, large randomized clinical trials are needed [ 5 ]. The zinc in powders trial (ZiPT) provided an opportunity to prospectively measure the effect of different forms of zinc supplementation on changes in EZP in a study population of young children at risk for zinc deficiency [ 6 , 7 ].…”

Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children

“…The present analysis is a sub-study of a randomized, controlled, partially blind, community-based efficacy trial comparing five different doses, frequencies and/or forms of preventive zinc supplementation to a placebo powder, provided for 24 weeks to children 9 to 11 months of age living in Dhaka, Bangladesh (clinicaltrials.gov NCT03406793) [ 10 ]. The primary outcomes of the parent trial were incidence of diarrhea and linear growth (change in length-for-age z-score (LAZ)), measured and analyzed according to the 2006 WHO Child Growth Standards [ 11 ].…”

“…Furthermore, we sought to assess whether peripheral blood gene expression could be used as a biomarker for zinc intervention status. In a sub-study of young children enrolled in a large randomized, controlled, community-based efficacy trial in Dhaka, Bangladesh [ 10 ], we undertook transcriptome-wide RNA sequencing and high-sensitivity cytokine analysis to define the effects of preventive zinc supplementation (provided as either a daily dispersible tablet or as a component of MNPs), in comparison with placebo powders, on peripheral blood gene expression and cytokine levels.…”