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

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

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.

Study Overview

• Status: Completed
• Conditions: Micronutrient Deficiencies
• Intervention / Treatment: Dietary supplement: MNP + Zn/Fe; Dietary supplement: MNP + Zn; Dietary supplement: Placebo

Detailed Description

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:

1. Characterizing the impact of enteral iron administration on the evolution of the intestinal microbiome in infants from 6 to 9 months of age.

2. 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:

   1. Intestinal inflammation;
   2. Systemic inflammation, bacterial translocation, and oxidant stress;
   3. Iron status and homeostasis
3. Quantify to what degree Fe interferes with Zn absorption (TAZ) and how it affects the size of the infant's exchangeable zinc pool (EZP).

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kenya
  • Eldoret, Kenya
    • Moi University
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 10 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); International Atomic Energy Agency; Moi University
• Investigators: Principal Investigator: Nancy F Krebs, MD, University of Colorado, Denver; Study Director: Fabian Esamai, MD, Moi Univeristy

Publications and helpful links

General Publications

• Esamai F, Liechty E, Ikemeri J, Westcott J, Kemp J, Culbertson D, Miller LV, Hambidge KM, Krebs NF. Zinc absorption from micronutrient powder is low but is not affected by iron in Kenyan infants. Nutrients. 2014 Dec;6(12):5636-51. doi: 10.3390/nu6125636.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: March 28, 2014
• First Submitted That Met QC Criteria: March 28, 2014
• First Posted (Estimate): April 2, 2014

Study Record Updates

• Last Update Posted (Actual): May 21, 2018
• Last Update Submitted That Met QC Criteria: May 18, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Microbiome; Kenya; Home fortification; Zinc absorption; Complementary foods; Micronutrient supplement
• Other Study ID Numbers: 11-0227; 16933 (IAEA); K24DK083772 (U.S. NIH Grant/Contract); 15827 (Other Grant/Funding Number: IAEA)