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

Completed

• Conditions: Environmental Enteric Dysfunction; Zinc Deficiency; Vitamin A Deficiency
• Interventions: Drug: 3 mg zinc sulfate supplement; Drug: 0.5 mg of 13C10-retinyl-acetate

• Registration Number: NCT02760095
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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.

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 Timeline

• Study First Submitted: 2015-07-24
• Study Start: 2015-11
• Study First Submitted QC: 2016-04-29
• Study First Posted: 2016-05-03
• Primary Completion: 2017-06
• Study Completion: 2017-06
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-27
• Last Update Posted: 2019-07-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Children with EED	3 mg zinc sulfate supplement	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).
Children with EED	0.5 mg of 13C10-retinyl-acetate	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).
Children without EED	3 mg zinc sulfate supplement	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).
Children without EED	0.5 mg of 13C10-retinyl-acetate	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).

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (2)

University of Colorado Denver School of Medicine; 🇺🇸 Aurora, Colorado, United States

icddr,b (International Centre for Diarrheal Disease Research, Bangladesh; 🇧🇩 Dhaka, Bangladesh