Effects of EED on Zn Absorption and Retention in Children From a Standard Dose (ZEED1)

Effects of Environmental Enteric Dysfunction (EED) on Zinc (Zn) Absorption and Retention in Young Children: Study 1 - Absorption of Zn and Vitamin A From a Standard Dose

The overall objective is to determine the impact of EED on zinc absorption and homeostasis, and its impact on the absorptive capacity of vitamin A absorption of young 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; Vitamin A Deficiency; Zinc Deficiency
• Intervention / Treatment: Drug: 3 mg zinc sulfate supplement; Drug: 0.5 mg of 13C10-retinyl-acetate

Detailed Description

Participating children are screened for EED using the lactulose:mannitol ratio test and assigned to one of two groups: +EED or -EED. All participants will be given standard, physiological dose of 3 mg zinc sulfate with a zinc stable isotope tracer on study day 8.

On study day 11, 0.5 mg of 13C10-retinyl-acetate will be administered orally to all participants.

Spot urine samples will be collected twice daily from study days 11-14. Complete fecal collections will be obtained for days 11-14. Duplicate diets of all foods consumed will be collected on days 11-14. On study day 14, a blood sample will be taken for analysis of vitamin A isotope status.

• Study Type: Observational
• Enrollment (Actual): 46

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 School of Medicine

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Toddlers aged 18-24 mos living in Dhaka, Bangladesh

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-score (LAZ) between -1.5 to -3.0
• Hemoglobin (Hgb) ≥ 8

Exclusion Criteria:

• Outside age range
• Hgb < 8
• Chronic illness
• Recent diarrhea (within past 2 weeks, treated with supplemental zinc)
• Severe stunting and/or severe acute malnutrition (SAM): LAZ <-3; Weight-for-age Z-score (WHZ) <-3 or mid-upper arm circumference (MUAC) < 115 or edema

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children with EED; Children are placed in this arm if they screen positive for EED using the urinary lactulose:mannitol (L:M) recovery ratio. Children will receive a one-time 3 mg standard dose of zinc sulfate with stable isotope zinc tracer and 0.5 mg standard dose of 13C10-retinyl-acetate (vitamin A isotope).	Drug: 3 mg zinc sulfate supplement; Drug: 0.5 mg of 13C10-retinyl-acetate; Other Names: Vitamin A isotope
Children without EED; Children are placed in this arm if they screen negative for EED using the urinary lactulose:mannitol (L:M) recovery ratio. Children will receive a one-time 3 mg standard dose of zinc sulfate with stable isotope zinc tracer and 0.5 mg standard dose of 13C10-retinyl-acetate (vitamin A isotope).	Drug: 3 mg zinc sulfate supplement; Drug: 0.5 mg of 13C10-retinyl-acetate; Other Names: Vitamin A isotope

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absorption of zinc (AZ) from standard dose	Absorption of zinc from standard 3 mg dose will be measured using zinc isotope tracer methods	1 day
Endogenous fecal zinc (EFZ)	EFZ measured from zinc isotope ratios in complete fecal collections	4 days
Vitamin A absorption	Absorption efficiency of retinol will be measured by isotope ratios in blood	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma zinc	Plasma zinc concentration	1 day
Alkaline phosphatase		1 day
Serum retinol		1 day
Methyl malonic acid	serum	1 day
Vitamin B12		1 day
Serum ferritin		1 day
Soluble transferrin receptors		1 day
C-reactive Protein (CRP)		1 day
Alpha-Glycoprotein (AGP)		1 day
Tumor necrosis factor (TNF) alpha		1 day
Serum endocab		1 day
Fecal neopterin		1 day
Myeloperoxidase		1 day
Alpha 1 antitrypsin		1 day
Calprotectin		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

• Mondal P, Long JM, Westcott JE, Islam MM, Ahmed M, Mahfuz M, Ahmed T, Miller LV, Krebs NF. Zinc Absorption and Endogenous Fecal Zinc Losses in Bangladeshi Toddlers at Risk for Environmental Enteric Dysfunction. J Pediatr Gastroenterol Nutr. 2019 Jun;68(6):874-879. doi: 10.1097/MPG.0000000000002361.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: July 24, 2015
• First Submitted That Met QC Criteria: April 29, 2016
• First Posted (Estimate): May 3, 2016

Study Record Updates

• Last Update Posted (Actual): July 1, 2019
• Last Update Submitted That Met QC Criteria: June 27, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: zinc; Bangladesh; vitamin A; environmental enteric dysfunction; environmental enteropathy
• Additional Relevant MeSH Terms: Eye Diseases; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vision Disorders; Night Blindness; Vitamin A Deficiency; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunologic Factors; Protective Agents; Dermatologic Agents; Micronutrients; Anti-Bacterial Agents; Adjuvants, Immunologic; Vitamins; Anticarcinogenic Agents; Astringents; Zinc Sulfate; Acetic Acid; Vitamin A; Retinol acetate
• Other Study ID Numbers: 14-2430A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No