Effect of Sprinkles With and w/o Fe on Zn Absorption in Kenyan Toddlers

Study Overview
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Brief Summary
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The investigators propose to study the effects of increased iron intake by home fortification of complementary foods on the gastrointestinal microbial development, inflammatory responses, and zinc (Zn) absorption. The proposed subjects are 9 month olds living in a malaria endemic area of rural Kenya who are randomized at 6 months of age to one of three fortificant groups: 1) Sprinkles™ with 12mg Iron(Fe)/day + other micronutrients, including 5mg/d Zn (test); Sprinkles™ with 0 mg/d Fe + other micronutrients, including 5mg/d Zn (control); Sprinkles™ with no micronutrients (placebo). The investigators hypothesize that the microbiome will be significantly different in the three groups and that Zn absorption and status, in addition to immune and oxidant status will be improved in the non-Fe fortified groups when compared to the Fe-fortified group.

Detailed Description
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Specific aims include exploration of possible mechanisms of adverse events that have been observed in iron supplementation trials in infants in malaria endemic regions by: Characterizing the impact of enteral iron administration on the evolution of the intestinal microbiome in infants from 6 to 9 months of age. Characterizing iron administration-associated inflammatory responses and correlate these with changes in the intestinal microbiome in infants from 6 to 9 months of age. Specifically, changes in the microbiome will be correlated with biomarkers reflecting: Intestinal inflammation; Systemic inflammation, bacterial translocation, and oxidant stress; Iron status and homeostasis Quantify to what degree Fe interferes with Zn absorption (TAZ) and how it affects the size of the infant's exchangeable zinc pool (EZP).

Official Title
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Effects of Sprinkles With and Without Iron on Zinc Absorption From Local Foods in Kenyan Toddlers, Including the Gut Microbiome

Conditions
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Micronutrient Deficiencies

Intervention / Treatment
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* Dietary Supplement: MNP + Zn/Fe
* Dietary Supplement: MNP + Zn
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Term infant Birthweight > 2500 g Healthy with no apparent congenital anomalies Up-to-date with vaccinations Hb >10 g/dL Breastfeeding with intent to continue for duration of study Negative blood slide for malaria Written informed consent Exclusion Criteria: Acute malnutrition Current or anticipated used of infant formula or other fortified products Current or planned use of iron (or zinc) supplements Previous hospitalization for malaria within the last four weeks Persistent diarrhea

Ages Eligible for Study
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Minimum Age: 5 Months
Maximum Age: 10 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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Micronutrient Powder (MNP) + Zn/Fe<br>Micronutrient Powder with 5 mg Zn and 12 mg Fe | Dietary Supplement: MNP + Zn/Fe<br>* Micronutrient powder with 12 mg Fe and 5 mg Zn provided daily from 6-9 months of age<br>|
| Active Comparator: MNP + Zn<br>Micronutrient Powder with 5 mg Zn | Dietary Supplement: MNP + Zn<br>* Micronutrient powder with 5 mg Zn provided daily from 6-9 months of age<br>|
| Placebo Comparator: Control<br>Placebo sachets without micronutrients | Dietary Supplement: Placebo<br>* Placebo powder without micronutrients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in GI microbiome | Identify and quantify the phylogenic distribution of bacterial genera in the infants from 6 to 9 months in prevalence or abundance with iron supplementation at baseline, mid-point and 9 months. | 6 and 9 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Biomarkers of intestinal and system inflammation | Compare mean baseline and 9 month values biomarkers of intestinal and systemic inflammation and look at differences among the 3 groups. | 6 and 9 months of age | 
| Absorption of Zn | Determine the effects of increased iron intake on zinc absorption from micronutrient powder added to local complementary foods of Kenyan toddlers in a malaria-endemic area. | 9 months of age | 
| Size of exchangeable Zn pool | Determine the effect of increase iron intake on size of exchangeable Zn pool (EZP) after 3 months of home fortification with micronutrient powder in maize-based diets in rural Kenyan infants. | 9 months of age | 
| Change in Biomarkers of bacterial translocation | To compare biomarkers of bacterial translocation among the 3 groups and look at longitudinal differences between 6 and 9 mo of age. | 6 and 9 mo of age | 
| Change in Biomarkers of oxidative stress | Compare biomarkers of oxidative stress among the 3 groups and look at longitudinal differences at 6 and 9 mo of age. | 6 and 9 mo of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zinc absorption, Micronutrient supplement, Kenya, Complementary foods, Home fortification, Microbiome