Iron and Prebiotics Fortification in Kenyan Infants

NCT02118402 | Completed DMC

• 1 other identifier: DSM-2-70790-11
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

Brief Summary

Iron deficiency and anemia are health issues affecting mainly infants and women in developing countries. Iron deficiency in infancy can have long-lasting impact on cognitive and motor development of the child. Iron fortification has shown to be effective against anemia. However, in areas with a high burden of infectious diseases iron may increase the risk of unfavorable gut microbiota composition possibly influencing diarrhea prevalence. Therefore we want to assess the effects of home fortification of complementary food with two iron-containing micronutrient powders (MNPs) with and without the addition of a prebiotic (7.5 g of galactooligosaccharides as GOS-75) compared to a control on the composition of the gut microbiota of Kenyan infants. In addition, iron deficiency may iimpair adaptive immunity. Following Kenyan Minstry of Health guidelines, infants receive their first measles vaccine at 9 months. In this study we will use an MNP with a moderate iron dose of 5 mg, with 2.5 mg of Fe as NaFeEDTA and 2.5 mg of Fe as ferrous fumarate (+Fe). There will be 3 study groups MNP, MNP+Fe and MNP+Fe+GOS. The infants will be enrolled in the study at the age of 6-10 months and will consume a home-fortified maize porridge for four months. At baseline and endpoint (after 4 months of intervention), we will collect blood samples of the infants in order to assess anemia, iron status, and inflammation. In addition, we will assess the effect of iron supplementation on measles vaccine response. Fecal samples (from child and mother) will be collected at baseline, 3 weeks and at endpoint in order to evaluate the changes in gut microbiota and gut inflammation. During the intervention, in a sub-group of children who receive broad-spectrum antibiotics, we will compare how the three different interventions modify the effect of antibiotics on the infant gut microbiota. We will opportunistically select children that are enrolled in the study and who become ill, and who are prescribed antibiotics by the local health care team, according to the local standard of care in the study area. Five additional stool samples from these children will be collected (day 0 (before the first antibiotic dose), 5, 10, 20 and 40) to evaluate the changes in the gut microbiota and gut inflammation. Three years after the study end, we would like to collect a blood and stool sample from the children and examine the iron status and gut microbiome respectively.

Conditions

Anemia; Iron Deficiency; Diarrhea; Malaria; Respiratory Tract Infections (RTI); Antibiotics; Gut Inflammation; Prebiotics; Vaccine Response

Outcome Measures

Primary Outcomes (1)

• The co-primary outcomes are the gut microbiome and gut inflammation

  We will measure key commensal and pathogenic members of the fecal gut microbiota of the infants using qPCR and 16S rDNA sequencing. We will measure fecal calprotectin and serum intestinal fatty acid binding protein as markers of gut inflammation and enterocyte injury. The changes in these measurements during the intervention will be compared among the three groups.

  Change from baseline to 3 weeks and 16 weeks

Secondary Outcomes (5)

• Iron status and systemic inflammation

  Change from baseline to endpoint (16 weeks)

• Anthropometry

  Change from baseline to endpoint (16 weeks)

• Child to -mother transmission of gut microbiota

  Change from baseline to 3 weeks and endpoint (16 weeks)

• Gut microbiota and gut inflammation during and after an oral antibiotic treatment

  Change from baseline day 0 (prior to antibiotic administration) to day 5, 10, 20 and 40

• Morbidity

  Weekly assessment from baseline to endpoint (16 weeks)

Other Outcomes (5)

• Human milk oligosaccharides in breast milk

  Sampling time points at week 3 and week 16

• Long term gut microbiota composition

  Change from endpoint to 3 years after study end

• Long term iron status and systemic inflammation

  Change from endpoint to 3 years after study end

Study Arms (3)

Fortified maize porridge (MNP)

ACTIVE COMPARATOR

The MNP contains 400 µg Vitamin A, 5 µg Vitamin D, 5 mg Tocopherol Equivalent, 0.5 mg Thiamine, 0.5 mg Riboflavin, 0.5 mg Vitamin B6 , 90 µg Folic Acid, 6 mg Niacin, 0.9 µg Vitamin B12, 30 mg Vitamin C, 0.56 mg Copper, 90 µg Iodine, 17 µg Selenium, 4.1 mg Zinc, 190 Phytase-units, maltodextrin carrier (added up to 11g)

Dietary Supplement: Fortified maize porridge

Fortified maize porridge (MNP+Fe)

ACTIVE COMPARATOR

The MNP contains 400 µg Vitamin A, 5 µg Vitamin D, 5 mg Tocopherol Equivalent, 0.5 mg Thiamine, 0.5 mg Riboflavin, 0.5 mg Vitamin B6 , 90 µg Folic Acid, 6 mg Niacin, 0.9 µg Vitamin B12, 30 mg Vitamin C, 0.56 mg Copper, 90 µg Iodine, 17 µg Selenium, 4.1 mg Zinc, 190 Phytase-units, plus 2.5 mg Fe as ferrous fumarate and 2.5 mg Fe as NaFeEDTA, maltodextrin carrier (added up to 11g)

Dietary Supplement: Fortified maize porridge

Fortified maize porridge (MNP+Fe+GOS)

ACTIVE COMPARATOR

The MNP contains 400 µg Vitamin A, 5 µg Vitamin D, 5 mg Tocopherol Equivalent, 0.5 mg Thiamine, 0.5 mg Riboflavin, 0.5 mg Vitamin B6 , 90 µg Folic Acid, 6 mg Niacin, 0.9 µg Vitamin B12, 30 mg Vitamin C, 0.56 mg Copper, 90 µg Iodine, 17 µg Selenium, 4.1 mg Zinc, 190 Phytase-units, 2.5 mg Fe as ferrous fumarate and 2.5 mg Fe as NaFeEDTA plus 7.5 g of galactooligosaccharides given as 10.5 g GOS-75, maltodextrin carrier (added up to 11g)

Dietary Supplement: Fortified maize porridge

Interventions

Fortified maize porridge DIETARY_SUPPLEMENT

Maize porridge will be home-fortified with either A) MNP, B) MNP+Fe, C) MNP+Fe+GOS

Fortified maize porridge (MNP); Fortified maize porridge (MNP+Fe); Fortified maize porridge (MNP+Fe+GOS)

Eligibility Criteria

• Age: 6 Months - 14 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age of 6-10 months at baseline
• Assessment of good health as assessed by professional staff at Kikoneni Health Clinic.
• Willingness of their caregiver to provide informed consent

You may not qualify if:

• Hemoglobin \<7g/dL; these participants will be referred for treatment at the local health clinic according to the guidelines of Kenya Ministry of Health.
• Participants taking part in other studies requiring the drawing of blood.
• Chronic or acute illness or other conditions that in the opinion of the PI or co-researchers would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol.
• Not planning long-term residence in study site
• Participants who are taking iron-containing food supplements or tablets/drops.

Sponsors & Collaborators

• Swiss Federal Institute of Technology: lead
• DSM Nutritional Products, Inc.: collaborator

Study Sites (1)

Kikoneni Health Center

Kikoneni, Kwale County, Kenya

Location

Related Publications (2)

• Paganini D, Uyoga MA, Kortman GAM, Cercamondi CI, Winkler HC, Boekhorst J, Moretti D, Lacroix C, Karanja S, Zimmermann MB. Iron-containing micronutrient powders modify the effect of oral antibiotics on the infant gut microbiome and increase post-antibiotic diarrhoea risk: a controlled study in Kenya. Gut. 2019 Apr;68(4):645-653. doi: 10.1136/gutjnl-2018-317399. Epub 2018 Nov 17.

  PMID: 30448776 DERIVED

• Paganini D, Uyoga MA, Kortman GAM, Cercamondi CI, Moretti D, Barth-Jaeggi T, Schwab C, Boekhorst J, Timmerman HM, Lacroix C, Karanja S, Zimmermann MB. Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron fortification on the gut microbiome: a randomised controlled study in Kenyan infants. Gut. 2017 Nov;66(11):1956-1967. doi: 10.1136/gutjnl-2017-314418. Epub 2017 Aug 3.

  PMID: 28774885 DERIVED

MeSH Terms

Conditions

Anemia; Iron Deficiencies; Diarrhea; Malaria; Respiratory Tract Infections

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Respiratory Tract Diseases

Study Officials

• Michael Zimmermann, MD

  ETH Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2014
• First Posted: April 21, 2014
• Study Start: July 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 5, 2020

Record last verified: 2020-02

Locations

KE (1)