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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Environmental Enteric Dysfunction, Zinc Deficiency, Vitamin A Deficiency

Intervention / Treatment
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* Drug: 3 mg zinc sulfate supplement
* Drug: 0.5 mg of 13C10-retinyl-acetate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children with EED<br>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<br> <br> Drug: 0.5 mg of 13C10-retinyl-acetate<br> <br> * Other names: Vitamin A isotope;|
| Children without EED<br>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<br> <br> Drug: 0.5 mg of 13C10-retinyl-acetate<br> <br> * Other names: Vitamin A isotope;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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environmental enteric dysfunction, environmental enteropathy, zinc, vitamin A, Bangladesh