Effects of EED on Zn Absorption and Retention in Children From a MNP (ZEED2)

Effects of Environmental Enteric Dysfunction (EED) on Zinc (Zn) Absorption and Retention in Young Children: Study 2 - Absorption of Zn From a Multi-micronutrient Powder (MNP)

The overall objective is to determine the impact of EED on total daily zinc absorption of young Bangladeshi children (18-24 months of age) in an austere setting with high rates of diarrhea, stunting, and micro-nutrient deficiencies..

Study Overview

• Status: Completed
• Conditions: Environmental Enteric Dysfunction; Zinc Deficiency
• Intervention / Treatment: Dietary supplement: Micronutrient Powder (MNP) + 15 mg Zn; Dietary supplement: MNP + 10 mg Zn; Dietary supplement: MNP + 5 mg Zn; Dietary supplement: MNP without Zn

Detailed Description

Participating children are screened for EED using the lactulose:mannitol ratio test and assigned to one of two groups: +EED or -EED. After assignment to one of the two groups, proposed subjects will be randomized to one of four supplement groups: Micronutrient powder (MNP) with 15 mg Zn, MNP with 10 mg Zn, MNP with 5 mg Zn, and MNP with 0 mg Zn. Children will receive the supplement once with a meal on Day 8 of the study. Absorption of zinc from the supplement and from other non-supplemented meals will be determined using zinc stable isotope technology.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • icddr,b (International Centre for Diarrheal Disease Research, Bangladesh
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Absence of apparent health problems that would impair ability to consume regular diet, to tolerate zinc supplements, or to comply with demands of metabolic studies
• Length for age Z (LAZ) score between -1.5 to -3.0
• Hg ≥ 8

Exclusion Criteria:

• Outside age range
• Hb < 8
• Chronic illness
• Zinc supplement within past 2 weeks (including for treatment of diarrhea or MNP containing zinc)
• Severe stunting and/or severe acute malnutrition (SAM): LAZ <-3; WHZ <-3 or MUAC < 115 or edema

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Micronutrient Powder (MNP) + 15 mg Zn; 1 sachet of Micronutrient Powder (MNP) + 15 mg Zn will be added to a single meal on study day 8	Dietary supplement: Micronutrient Powder (MNP) + 15 mg Zn; Children will have the supplement powder added to one meal on study day 1. Absorption of zinc from this meal will be measured using zinc stable isotope techniques.
Active Comparator: MNP + 10 mg Zn; 1 sachet of MNP + 10 mg Zn will be added to a single meal on study day 8	Dietary supplement: MNP + 10 mg Zn; Same as above except MNP will contain 10 mg Zn
Active Comparator: MNP + 5 mg Zn; 1 sachet of MNP + 5 mg Zn will be added to a single meal on study day 8	Dietary supplement: MNP + 5 mg Zn; Same as above except MNP will contain 5 mg Zn
Placebo Comparator: MNP without Zn; 1 sachet of MNP without Zn will be added to a single meal on study day 8	Dietary supplement: MNP without Zn; Same as above except MNP will not contain Zn

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total daily absorbed zinc (TAZ)	Measured during the meal to determine the effects of EED on zinc absorption.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exchangeable zinc pool (EZP)	Size of exchangeable Zn pool (EZP) measured with zinc isotope methods prior to the meal.	1 day
Plasma zinc	Measured prior to the meal.	1 day
Alkaline phosphatase	Measured prior to the meal.	1 day
Serum retinol	Measured prior to the meal.	1 day
Methyl malonic acid	Measured prior to the meal.	1 day
Vitamin B12	Measured prior to the meal.	1 day
Serum ferritin	Measured prior to the meal.	1 day
Soluble transferrin receptors	Measured prior to the meal.	1 day
CRP	Measured prior to the meal.	1 day
AGP	Measured prior to the meal.	1 day
TNF alpha	Measured prior to the meal.	1 day
Serum endocab	Measured prior to the meal.	1 day
Neopterin	Measured prior to the meal.	1 day
Myeloperoxidase	Measured prior to the meal.	1 day
Calprotectin	Measured prior to the meal.	1 day
alpha 1 antitrypsin	Measured prior to the meal.	1 day

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: International Centre for Diarrhoeal Disease Research, Bangladesh
• Investigators: Principal Investigator: Nancy F Krebs, MD, MS, University of Colorado, Denver

Publications and helpful links

General Publications

• Long JM, Mondal P, Westcott JE, Miller LV, Islam MM, Ahmed M, Mahfuz M, Ahmed T, Krebs NF. Zinc Absorption from Micronutrient Powders Is Low in Bangladeshi Toddlers at Risk of Environmental Enteric Dysfunction and May Increase Dietary Zinc Requirements. J Nutr. 2019 Jan 1;149(1):98-105. doi: 10.1093/jn/nxy245.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: April 27, 2016
• First Submitted That Met QC Criteria: April 28, 2016
• First Posted (Estimate): May 2, 2016

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 1, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Bangladesh; toddlers; environmental enteric dysfunction; environmental enteropathy; zinc absorption; zinc isotope
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Trace Elements
• Other Study ID Numbers: 14-2430B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes