Prebiotic GOS and Lactoferrin With Iron Supplements

NCT03866837 | Completed Results DMC

• 2 other identifiers: AAAR8900R01DK115449
• Study Type: interventional
• Target: 288
• Locations: 2 countries
• Sites: 2

Brief Summary

The ultimate goal of this research is to develop a means to safely administer iron supplements to infants in settings with a high infection burden. The investigators will conduct a randomized clinical trial in 6 month-old Kenyan infants in conjunction with mechanistic microbiota studies using a novel long-term continuous polyfermenter platform inoculated with immobilized fecal microbiota from Kenyan infants. Oral iron supplements are associated with a significant 15% increase in the rate of diarrhea in children in malaria-endemic areas. The most recent studies have shown that prebiotic galacto-oligosaccharides (GOS) can provide partial amelioration of the adverse effects of iron supplementation by enhancing the growth of barrier populations of bifidobacteria and lactobacilli. The investigators hypothesize that the combination of GOS with bovine lactoferrin, adding iron sequestration as well as antimicrobial and immunomodulatory activities, will provide almost complete protection against the adverse effects of added iron on the intestinal microbiota.

Conditions

Iron-deficiency

Keywords

Iron-deficiency; Iron supplementation; Galacto-oligosaccharides; Lactoferrin; Ferrous fumarate; Clinical trial; Microbiome; PolyFermS; Polyfermenter intestinal model

Outcome Measures

Primary Outcomes (1)

• Ratio of Harmful to Beneficial Bacterial Genera in Fecal Microbiota as Determined by Quantitative Polymerase Chain Reaction (qPCR) at 1 Month

  The primary outcome measure will be the ratio of the abundances of potentially harmful (enteropathogenic and/or enterotoxigenic E. coli, C. difficile, members of the C. perfringens group, B. cereus, S. aureus, sum of Shigella spp., and Salmonella) to beneficial (bifidobacteria and the group of Lactobacillus/Leuconostoc/Pediococcus spp.) bacterial genera in fecal microbiota as determined by quantitative polymerase chain reaction (qPCR) at 1 month.

  1 month

Secondary Outcomes (11)

• Ratio of Harmful to Beneficial Bacterial Genera in Fecal Microbiota as Determined by Quantitative Polymerase Chain Reaction (qPCR) at 6 Months

  6 months

• Ratio of Harmful to Beneficial Bacterial Genera in Fecal Microbiota as Determined by Quantitative Polymerase Chain Reaction (qPCR) at 9 Months

  9 months

• Microbiota Composition as Determined by Quantitative Polymerase Chain Reaction (qPCR).

  1, 6 and 9 months

• Number of Participants Who Experienced Diarrhea

  Up to 9 months

• Number of Participants Who Experienced Malaria

  Up to 9 months

Study Arms (4)

Study group A: GOS

ACTIVE COMPARATOR

This study group will receive daily in-home fortification for 6 months with multiple micronutrient powders with 5 mg iron (as sodium iron EDTA \[2.5 mg\] and ferrous fumarate \[2.5 mg\]) and galacto-oligosaccharides (GOS), 7.5 mg.

Dietary Supplement: Galacto-oligosaccharides; Dietary Supplement: Multiple micronutrient powders with 5 mg iron

Study group B: bLF

ACTIVE COMPARATOR

This study group will receive daily in-home fortification for 6 months with multiple micronutrient powders with 5 mg iron (as sodium iron EDTA \[2.5 mg\] and ferrous fumarate \[2.5 mg\]), bovine lactoferrin (bLF), 1.0 g.

Dietary Supplement: Bovine lactoferrin; Dietary Supplement: Multiple micronutrient powders with 5 mg iron

Study group C: GOS + bLF

ACTIVE COMPARATOR

This study group will receive daily in-home fortification for 6 months with multiple micronutrient powders with 5 mg iron (as sodium iron EDTA \[2.5 mg\] and ferrous fumarate \[2.5 mg\]), galacto-oligosaccharides (GOS), 7.5 mg, and bovine lactoferrin (bLF), 1.0 g.

Dietary Supplement: Galacto-oligosaccharides; Dietary Supplement: Bovine lactoferrin; Dietary Supplement: Multiple micronutrient powders with 5 mg iron

Study group D

PLACEBO COMPARATOR

This study group will receive daily in-home fortification for 6 months with multiple micronutrient powders with 5 mg iron (as sodium iron EDTA \[2.5 mg\] and ferrous fumarate \[2.5 mg\]) alone, with no galacto-oligosaccharides (GOS), and no bovine lactoferrin (bLF).

Dietary Supplement: Multiple micronutrient powders with 5 mg iron

Interventions

Galacto-oligosaccharides DIETARY_SUPPLEMENT

Galacto-oligosaccharides are classified as Generally Recognized As Safe (GRAS) by the U.S. Food and Drug Administration, are components of cow's milk and have been used repeatedly in clinical trials without adverse effects.

Study group A: GOS; Study group C: GOS + bLF

Bovine lactoferrin DIETARY_SUPPLEMENT

Bovine lactoferrin is classified as Generally Recognized As Safe (GRAS) by the U.S. Food and Drug Administration, is a component of cow's milk and has been used repeatedly in clinical trials without adverse effects.

Study group B: bLF; Study group C: GOS + bLF

Multiple micronutrient powders with 5 mg iron DIETARY_SUPPLEMENT

The multiple micronutrient powders are composed of Vitamin A, 400 μg; Vitamin D, 5 μg; Tocopherol Equivalents, 5 mg; Thiamine, 0.5 mg; Riboflavin, 0.5 mg; Vitamin B6, 0.5 mg; Folic Acid, 90 μg; Niacin, 6 mg; Vitamin B12, 0.9 μg; Vitamin C, 30 mg; Copper, 0.56 mg; Iodine, 90 μg; Selenium, 17 μg; Zinc, 4.1 mg; Phytase, 190 FTU; Iron, 5 mg \[(as Ferrous fumarate, 2.5 mg and sodium iron ethylenediaminetetraacetate (NaFeEDTA), 2.5 mg\].

Study group A: GOS; Study group B: bLF; Study group C: GOS + bLF; Study group D

Eligibility Criteria

• Age: 21 Weeks - 27 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• vaginal or cesarean delivery
• an infant age of 6 months (±3 weeks)
• mother ≥15 years of age
• infant still breastfeeding
• anticipated residence in the area for the study duration.

You may not qualify if:

• inability to provide informed consent
• hemoglobin \< 70 g/L
• Z scores for weight-for-age (WAZ) or weight-for-height (WHZ) \<3,
• any maternal or infant chronic illness
• administration of any infant vitamin or mineral supplements for the past 2 months
• history of infant antibiotic treatment within 7 days before study enrollment.

Sponsors & Collaborators

• Columbia University: lead
• Swiss Federal Institute of Technology: collaborator
• Jomo Kenyatta University of Agriculture and Technology: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Jomo Kenyatta University of Agriculture and Technology

Nairobi, 00200, Kenya

Location

Swiss Federal Institute of Technology (ETH Zürich)

Zurich, 8092, Switzerland

Location

Related Publications (27)

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MeSH Terms

Conditions

Anemia, Iron-Deficiency

Interventions

Iron

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Results Point of Contact

• Title: Gary M. Brittenham, M.D.
• Organization: Columbia University

gmb31@cumc.columbia.edu

212 305 7005

Study Officials

• Gary M Brittenham, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Stratified randomization will be carried out by the Trial Statistician using computer-generated randomly permuted blocks of size 2, 4 or 6 with stratification by gender and assignment of eligible infants to one of the 4 intervention groups using 4 color codes. Allocation will be known solely by the Trial Statistician and the Clinical Trial Safety Officer and concealed from all other study personnel.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Medicine

Model Details: The study is a single-center, double-blinded, randomized, 9-month clinical trial with a 2X2 factorial design to determine the efficacy of galacto-oligosaccharides and bovine lactoferrin in preserving a beneficial gut microbiota during iron supplementation in Kenyan infants.

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 7, 2019
• Study Start: January 15, 2020
• Primary Completion: April 30, 2023
• Study Completion: April 30, 2023
• Last Updated: January 8, 2025
• Results First Posted: January 8, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

KE (1); CH (1)