Iron Absorption From a Micronutrient Powder Containing Galacto-oligosaccharides (GOS)

Anemia, Iron-Deficiency Clinical Trial

— FeGOS  

Official title:

Testing Iron Absorption From a New Micronutrient Powder Containing Galacto-oligosaccharides (GOS) for Fortification of Infant Foods in Sub-Saharan Africa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02666417
• Other study ID #: FeGOS_KP
• Status: Completed
• Phase: N/A
• Start date: January 2016
• Est. completion date: December 2016

Study information

• Verified date: July 2018
• Source: Swiss Federal Institute of Technology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Infants and young children in sub-Saharan Africa have high rates of iron deficiency anemia (IDA), which adversely affects their growth and cognitive development. In-home iron fortification of complementary foods using micronutrient powders (MNPs) reduces risk for IDA. However, in areas with a high burden of infectious diseases iron may increase the risk of unfavorable gut microbiota composition possibly influencing diarrhea prevalence. Thus, there is an urgent need to find safer formulations of iron fortification for African infants. The investigators recently finished a randomized, double blind controlled intervention trial in Kenya where the investigators tested whether the addition of galacto-oligosaccharides (GOS) in a MNP containing 5 mg of iron protects against the adverse effects of the iron on the infant gut microbiome and gut inflammation (ClincalTrails.gov Identifier: NCT02118402). Prebiotics are also potential enhancers of colonic iron absorption. Therefore, to complement the intervention study, the present study will compare iron absorption from the combination of sodium iron EDTA (NaFeEDTA) and ferrous fumarate (FeFum) with and without prior consumption GOS or 3 weeks. The investigators will enroll 80 Kenyan infants from Kwale County, aged 6-14 months of whom 40 infants will consume maize porridge blended with MNP containing iron and 40 infants will receive a porridge mixed with MNP containing iron+GOS. After 3 weeks of MNP consumption, two test meals will be fed on two consecutive mornings, and will consist of maize porridge containing isotopically labeled FeFum and NaFeEDTA or isotopically labeled ferrous sulfate (FeSO₄), respectively. Fourteen days after the second test meal administration, a whole blood sample will be collected by venipuncture for iron isotopic analysis. Iron and inflammation status parameter will be determined at baseline and endpoint. A stool sample will be collected at baseline and on the first test meal day. The gut microbiome, fecal pH and fecal SCFAs profile will be analyzed. Knowing the expected iron absorption from the iron and GOS containing MNP will inform decisions on type of iron compound and dosing regimens for MNPs to allow the lowest iron dose to be used but still cover the infant requirement for absorbed iron.

Description:

Iron absorption from two iron-fortified maize-based test meals will be measured in two groups of 40 infants (total N=80). Infants will be recruited at Msambweni District Hospital and communities served by Msambweni District Hospital in southern coastal Kenya. In group 1, iron absorption is measured after 3 weeks of MNP consumption containing 5 mg iron in form of NaFeEDTA (2.5 g) and FeFum (2.5 g) but no GOS. In group 2, iron absorption is measured after 3 weeks of MNP consumption containing 5 mg iron in form of NaFeEDTA (2.5 g) and FeFum (2.5 g) and 7.5 g GOS. Iron absorption is measured as the incorporation of stable isotopes into erythrocytes at least 14 days after the test meal administration.

At baseline, a blood sample will be collected from potential study participants for the determination of the following iron and inflammation status parameters: hemoglobin (Hb), plasma ferritin (PF), soluble transferrin receptor (sTfR), zinc protoporphyrin (ZnPP), C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP). Anthropometrics (height, weight, mid-upper arm and head circumference) will be measured, and demographics, the medical history and the feeding habits will be assessed using a questionnaire. On day 1, infants will be enrolled and randomized into the two groups, and then start the intervention. The infants will consume 1 MNP sachet added to maize porridge per day for a total of 5 weeks. A stool sample will be collected on day 1 for the determination of gut microbiota composition, fecal pH and fecal SCFAs. After 3 weeks of MNP consumption, the two isotopically labelled test meals will be fed to the infants by their caregivers under supervision of the research team on two consecutive mornings between 7 and 8 am. Test meal A will contain 2.5 mg 57Fe in form of FeFum and 2.5 mg iron as NaFeEDTA (given as 1.5 mg 56Fe and 1 mg 58Fe). Test meal B will contain 5 mg iron in form of FeSO₄ (3 mg of 56Fe and 2 mg of 54Fe). The test meals will consist of maize porridge (5-10% dry weight) and mineral water (30 ml) and will be randomly administered on the two consecutive days (AB or BA). Overnight, only breast milk will be allowed to the infant and no breast milk will be given at least 3 h before test meal administration. Infants will not be allowed to eat or drink for 2 h after the test meal. On the day of the first test meal, a stool sample will be collected and analyzed for gut microbiota composition, fecal pH and fecal SCFAs. Fourteen days after the second test meal administration, 3 ml of whole blood will be collected by venipuncture for iron isotopic analysis and iron and inflammation status. Anthropometrics and the baseline questionnaire will be repeated. Compliance of MNP consumption and adverse event reporting (morbidity monitoring) will be done during weekly visits of the infants.

In a follow-on study, iron absorption from the two above described mentioned iron-fortified maize-based test meals will be measured in 24 infants aged 6-12 months without pre-feeding of GOS. All procedures will be done identical as described above.

Other known NCT identifiers

• NCT03357510

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: December 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 14 Months

Eligibility

Inclusion Criteria:

• Age of 6-14 months at baseline

• Assessment of good health as assessed by professional staff at Msambweni District Hospital

• Willingness of their caregiver to provide informed consent

Exclusion Criteria:

• Hemoglobin <70 g/L ; these infants will be referred for treatment according to local standard of care.

• Severe underweight (Z-score weight-for-age <-3) and /or severe wasting (Z-score weight-for-height<-3)

• Chronic or acute illness or other conditions that in the opinion of the Principle Investigator (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

• Participants taking part in other studies requiring the drawing of blood

• Participants who are taking iron-containing food supplements or tablets/drops

• Participants who are taking antibiotics

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency

Intervention

Dietary Supplement:
• Fortified maize porridge (MNP+iron)
Maize porridge will be home-fortified with the MNP + iron. Maize porridge for the test meal will be fortified with labelled iron compounds
• Fortified maize porridge (MNP+iron+GOS)
Maize porridge will be home-fortified with the MNP + iron + GOS. Maize porridge for the test meal will be fortified with labelled iron compounds

Locations

Country	Name	City	State
Kenya	Msambweni District Hopsital	Msambweni	Kwale County

Sponsors (4)

Lead Sponsor	Collaborator
Swiss Federal Institute of Technology	International Centre for Behavioural Studies, Jomo Kenyatta University of Agriculture and Technology, Msambweni District Hospital

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in the isotopic ratio of iron in blood at week 5	The change in the isotopic ratio of iron will be measured after the administration of test meals including iron isotopes.	Baseline and Week 5
Secondary	Gut microbiome composition	The changes in the gut microbiome composition from baseline to week 3 will be compared among the two groups and correlated to the iron absorption from the test meal.	Baseline and Week 3
Secondary	Fecal pH	The changes in fecal pH from baseline to week 3 will be compared among the two groups and correlated to the iron absorption from the test meal.	Baseline and Week 3
Secondary	Fecal short chain fatty acids (SCFAs)	The changes in SCFAs from baseline to week 3 will be compared among the two groups and correlated to the iron absorption from the test meal.	Baseline and Week 3
Secondary	H.pylori	H.pylori infection as determinant of iron absorption	Baseline