Iron-deficiencyNCT03866837

Prebiotic GOS and Lactoferrin With Iron Supplements

A study testing Galacto-oligosaccharides, Bovine lactoferrin and Multiple micronutrient powders with 5 mg iron in people with Iron-deficiency, run by Columbia University at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 21 to 27 weeksHealthy volunteers can take part
Conditions the study is for: Iron-deficiency
What is being tested?: Galacto-oligosaccharides, Bovine lactoferrin and Multiple micronutrient powders with 5 mg iron
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 288 participants
Where: 2 sitesin 2 countries
Study dates: 15 Jan 2020to 30 Apr 2023
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 27 weeks
All sexes
Healthy volunteers accepted
Child

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

2 sites in 2 countries.

Country

City, postcode or hospital

2 sites in 2 countries

Kenya1 site

Jomo Kenyatta University of Agriculture and Technology
Nairobi, 00200

Other trials in Kenya

Switzerland1 site

Swiss Federal Institute of Technology (ETH Zürich)
Zurich, 8092

Other trials in Switzerland

About this study

Official title: Prebiotic GOS and Lactoferrin for Beneficial Gut Microbiota With Iron Supplements

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.

Read the detailed description

Iron deficiency, the principal cause of anemia globally, affects more than two billion individuals, predominantly infants, children and women of childbearing age. Iron deficiency impairs cognitive and behavioral development in childhood, compromises immune responsiveness, decreases physical performance, and when severe, increases mortality among infants, children and pregnant women. Effective prevention and treatment of iron deficiency uses iron supplements or fortificants to increase oral iron intake. Generally, only a small fraction of the added iron is absorbed in the upper small intestine, with 80% or more passing into the colon. Because iron is an essential micronutrient for growth, proliferation, and persistence for most intestinal microbes, the increase in iron availability has profound effects on the composition and metabolism of intestinal microbiota. In particular, iron is a prime determinant of colonization and virulence for most enteric gram-negative bacteria, includingmSalmonella, Shigella and pathogenic Escherichia coli. Commensal intestinal microorganisms, principally of the genera Bifidobacterium and Lactobacillus, require little or no iron, provide a barrier effect and can inhibit pathogen growth by a variety of methods, including sequestration of iron, competition for nutrients and for intestinal epithelial sites stabilization of intestinal barrier function, and production of antibacterial peptides and organic acids that lower the pH. Increases in unabsorbed iron can promote the growth of virulent enteropathogens that overwhelm barrier strains and disrupt the gut microbiota.

We hypothesize that the combination of prebiotic GOS with bovine lactoferrin (bLF), adding iron sequestration, antimicrobial and immunomodulatory activities, will provide virtually complete protection against the adverse effects of added iron on the intestinal microbiota. Our research has two specific aims:

to conduct a randomized, controlled double-blind 9-month clinical trial in 6-month old Kenyan infants comparing the effects on gut microbiome composition among groups receiving in-home fortification for 6 months with micronutrient powders containing 5 mg iron (as sodium iron EDTA [2.5 mg] and ferrous fumarate [2.5 mg]) and (i) galacto-oligosaccharides (GOS; 7.5 g), (ii) bovine lactoferrin (bLF, 1.0 g), (iii) GOS (7.5 g) and bLF (1.0 g), and (iv) no GOS or bLF. Each infant will then be followed for an additional 3 months to determine the longer-term effects of the treatments.
to examine mechanisms of iron, prebiotic GOS and iron-sequestering bLF on microbiota composition, enteropathogen development, microbiota functions and metabolic activity, and inflammatory potential in vitro with treatments paralleling those in Specific Aim 1, using immobilized fecal microbiota from Kenyan infants to inoculate our established long-term continuous polyfermenter intestinal model (PolyFermS) to mimic Kenyan infant colon conditions, together with cellular studies.

Combining in vivo clinical and in vitro approaches will help guide formulation of safer iron supplements and fortificants and improve our understanding of the mechanisms whereby prebiotic GOS and iron-sequestering bLF support commensal microbiota to prevent iron-induced overgrowth by opportunistic enteropathogens.

Conditions: Iron-deficiency
Being tested: Galacto-oligosaccharides, Bovine lactoferrin, Multiple micronutrient powders with 5 mg iron
Keywords: Iron-deficiency, Iron supplementation, Galacto-oligosaccharides, Lactoferrin, Ferrous fumarate, Clinical trial, Microbiome, PolyFermS, Polyfermenter intestinal model
Medical subject headings: Anemia, Iron-Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Galacto-oligosaccharidesDietary 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.
Bovine lactoferrinDietary 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.
Multiple micronutrient powders with 5 mg ironDietary 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 groups in NCT03866837
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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). Receives: Dietary Supplement: Multiple micronutrient powders with 5 mg iron

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
A key secondary 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 6 months.
Measured: 6 months
Ratio of Harmful to Beneficial Bacterial Genera in Fecal Microbiota as Determined by Quantitative Polymerase Chain Reaction (qPCR) at 9 Months
A key secondary 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 9 months.
Measured: 9 months
Microbiota Composition as Determined by Quantitative Polymerase Chain Reaction (qPCR).
A secondary outcome measure will be the microbiota composition among study groups as determined by quantitative polymerase chain reaction (qPCR) measures 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) and of beneficial (bifidobacteria and the group of Lactobacillus/Leuconostoc/Pediococcus spp.) bacterial genera at 1, 6, and 9 months. This outcome is reported as the mean log10 fold change from the beneficial to harmful bacteria ratio (BHR) of the baseline microbiota composition, abbreviated as "log10 FC in BHR".
Measured: 1, 6 and 9 months
Number of Participants Who Experienced Diarrhea
A secondary outcome measure will be the prevalence of diarrhea among study groups.
Measured: Up to 9 months
Number of Participants Who Experienced Malaria
A secondary outcome measure will be the prevalence of malaria among study groups.
Measured: Up to 9 months
Proportion of Participants Who Experienced Anemia
A secondary outcome measure will be the proportion of participants with anemia among study groups, defined as Hemoglobin < 11.5 g/L by laboratory diagnosis.
Measured: Baseline, 1 month, 6 months, 9 months
Proportion of Participants Who Experienced Iron Deficiency
A secondary outcome measure will be the proportion of participants with iron deficiency among study groups, defined as plasma Ferritin < 12 µg/L or/and soluble transferrin receptor (sTfR) > 8.3 mg/L
Measured: Baseline, 1 month, 6 months, 9 months
Proportion of Participants Who Experienced Iron Deficiency Anemia (IDA)
A secondary outcome measure will be the proportion of participants with iron deficiency anemia among study groups, defined as Hemoglobin < 11.5 g/L and Soluble transferrin receptor (sTfR) > 8.3 mg/L
Measured: Baseline, 1 month, 6 months, 9 months
Proportion of Participants Who Experienced Inflammation
A secondary outcome measure will be the proportion of participants with inflammation among study groups, defined as C-reactive protein (CRP) > 5 mg/L
Measured: Baseline, 1 month, 6 months, 9 months
Number of Participants Who Experienced Respiratory Tract Infections
A secondary outcome measure will be the prevalence of Respiratory tract infections among study groups.
Measured: Up to 9 months
Other Illnesses
A secondary outcome measure will be the prevalence of other illnesses among study groups.
Measured: Up to 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Jan 202030 Apr 2023

First posted7 Mar 2019
Study start15 Jan 2020
Primary completion30 Apr 2023
Study completion30 Apr 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (27)Papers the sponsor has linked to this study.
Other trials for Iron-deficiencyStudies of the same condition, open and under way.
More trials run by Columbia UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Model description: 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.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 288 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03866837
Sponsor's protocol ID: AAAR8900
Other IDs: R01DK115449
Status last verified: Dec 2024
First submitted: 4 Mar 2019
Last updated: 8 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Jaeggi T, Kortman GA, Moretti D, Chassard C, Holding P, Dostal A, Boekhorst J, Timmerman HM, Swinkels DW, Tjalsma H, Njenga J, Mwangi A, Kvalsvig J, Lacroix C, Zimmermann MB. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut. 2015 May;64(5):731-42. doi: 10.1136/gutjnl-2014-307720. Epub 2014 Aug 20.
PubMed 25143342
Paganini D, Uyoga MA, Zimmermann MB. Iron Fortification of Foods for Infants and Children in Low-Income Countries: Effects on the Gut Microbiome, Gut Inflammation, and Diarrhea. Nutrients. 2016 Aug 12;8(8):494. doi: 10.3390/nu8080494.
PubMed 27529276
Zimmermann MB, Chassard C, Rohner F, N'goran EK, Nindjin C, Dostal A, Utzinger J, Ghattas H, Lacroix C, Hurrell RF. The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire. Am J Clin Nutr. 2010 Dec;92(6):1406-15. doi: 10.3945/ajcn.110.004564. Epub 2010 Oct 20.
PubMed 20962160
Dostal A, Chassard C, Hilty FM, Zimmermann MB, Jaeggi T, Rossi S, Lacroix C. Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats. J Nutr. 2012 Feb;142(2):271-7. doi: 10.3945/jn.111.148643. Epub 2011 Dec 21.
PubMed 22190022
Dostal A, Fehlbaum S, Chassard C, Zimmermann MB, Lacroix C. Low iron availability in continuous in vitro colonic fermentations induces strong dysbiosis of the child gut microbial consortium and a decrease in main metabolites. FEMS Microbiol Ecol. 2013 Jan;83(1):161-75. doi: 10.1111/j.1574-6941.2012.01461.x. Epub 2012 Aug 28.
PubMed 22845175
Dostal A, Lacroix C, Pham VT, Zimmermann MB, Del'homme C, Bernalier-Donadille A, Chassard C. Iron supplementation promotes gut microbiota metabolic activity but not colitis markers in human gut microbiota-associated rats. Br J Nutr. 2014 Jun 28;111(12):2135-45. doi: 10.1017/S000711451400021X. Epub 2014 Feb 21.
PubMed 24555487
Dostal A, Gagnon M, Chassard C, Zimmermann MB, O'Mahony L, Lacroix C. Salmonella adhesion, invasion and cellular immune responses are differentially affected by iron concentrations in a combined in vitro gut fermentation-cell model. PLoS One. 2014 Mar 27;9(3):e93549. doi: 10.1371/journal.pone.0093549. eCollection 2014.
PubMed 24676135
Dostal A, Lacroix C, Bircher L, Pham VT, Follador R, Zimmermann MB, Chassard C. Iron Modulates Butyrate Production by a Child Gut Microbiota In Vitro. mBio. 2015 Nov 17;6(6):e01453-15. doi: 10.1128/mBio.01453-15.
PubMed 26578675
Lacroix C, de Wouters T, Chassard C. Integrated multi-scale strategies to investigate nutritional compounds and their effect on the gut microbiota. Curr Opin Biotechnol. 2015 Apr;32:149-155. doi: 10.1016/j.copbio.2014.12.009. Epub 2015 Jan 3.
PubMed 25562815
Payne AN, Zihler A, Chassard C, Lacroix C. Advances and perspectives in in vitro human gut fermentation modeling. Trends Biotechnol. 2012 Jan;30(1):17-25. doi: 10.1016/j.tibtech.2011.06.011. Epub 2011 Jul 20.
PubMed 21764163
Payne AN, Chassard C, Banz Y, Lacroix C. The composition and metabolic activity of child gut microbiota demonstrate differential adaptation to varied nutrient loads in an in vitro model of colonic fermentation. FEMS Microbiol Ecol. 2012 Jun;80(3):608-23. doi: 10.1111/j.1574-6941.2012.01330.x. Epub 2012 Mar 27.
PubMed 22324938
Tanner SA, Zihler Berner A, Rigozzi E, Grattepanche F, Chassard C, Lacroix C. In vitro continuous fermentation model (PolyFermS) of the swine proximal colon for simultaneous testing on the same gut microbiota. PLoS One. 2014 Apr 7;9(4):e94123. doi: 10.1371/journal.pone.0094123. eCollection 2014.
PubMed 24709947
Zihler Berner A, Fuentes S, Dostal A, Payne AN, Vazquez Gutierrez P, Chassard C, Grattepanche F, de Vos WM, Lacroix C. Novel Polyfermentor intestinal model (PolyFermS) for controlled ecological studies: validation and effect of pH. PLoS One. 2013 Oct 30;8(10):e77772. doi: 10.1371/journal.pone.0077772. eCollection 2013.
PubMed 24204958
Pasricha SR, Hayes E, Kalumba K, Biggs BA. Effect of daily iron supplementation on health in children aged 4-23 months: a systematic review and meta-analysis of randomised controlled trials. Lancet Glob Health. 2013 Aug;1(2):e77-e86. doi: 10.1016/S2214-109X(13)70046-9. Epub 2013 Jul 24.
PubMed 25104162
Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, Regan M, Weatherall D, Chou DP, Eisele TP, Flaxman SR, Pullan RL, Brooker SJ, Murray CJ. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014 Jan 30;123(5):615-24. doi: 10.1182/blood-2013-06-508325. Epub 2013 Dec 2.
PubMed 24297872

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Iron-deficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Prebiotic GOS and Lactoferrin for Beneficial Gut Microbiota With Iron Supplements
ClinicalTrials.gov ID: NCT03866837
Acronym / sponsor ID: AAAR8900
Conditions: Iron-deficiency
Keywords: Iron-deficiency, Iron supplementation, Galacto-oligosaccharides, Lactoferrin, Ferrous fumarate, Clinical trial, Microbiome, PolyFermS
Study type: Interventional
Recruitment status: Completed
Enrolment: 288 participants (actual)
Lead sponsor: Columbia UniversityUniversity, hospital or other
Collaborators: Swiss Federal Institute of Technology, Jomo Kenyatta University of Agriculture and Technology, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study start: 15 Jan 2020 (actual)
Primary completion: 30 Apr 2023 (actual)
Study completion: 30 Apr 2023 (actual)
First posted: 7 Mar 2019 (actual)
Results: Posted 8 Jan 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

to conduct a randomized, controlled double-blind 9-month clinical trial in 6-month old Kenyan infants comparing the effects on gut microbiome composition among groups receiving in-home fortification for 6 months with micronutrient powders containing 5 mg iron (as sodium iron EDTA [2.5 mg] and ferrous fumarate [2.5 mg]) and (i) galacto-oligosaccharides (GOS; 7.5 g), (ii) bovine lactoferrin (bLF, 1.0 g), (iii) GOS (7.5 g) and bLF (1.0 g), and (iv) no GOS or bLF. Each infant will then be followed for an additional 3 months to determine the longer-term effects of the treatments.
to examine mechanisms of iron, prebiotic GOS and iron-sequestering bLF on microbiota composition, enteropathogen development, microbiota functions and metabolic activity, and inflammatory potential in vitro with treatments paralleling those in Specific Aim 1, using immobilized fecal microbiota from Kenyan infants to inoculate our established long-term continuous polyfermenter intestinal model (PolyFermS) to mimic Kenyan infant colon conditions, together with cellular studies.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4
Model description: 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.

Arm	Type	Receives
Study group A: GOS	Active comparator	Dietary Supplement: Galacto-oligosaccharides, Dietary Supplement: Multiple micronutrient powders with 5 mg ironThis 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.
Study group B: bLF	Active comparator	Dietary Supplement: Bovine lactoferrin, Dietary Supplement: Multiple micronutrient powders with 5 mg ironThis 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.
Study group C: GOS + bLF	Active comparator	Dietary Supplement: Galacto-oligosaccharides, Dietary Supplement: Bovine lactoferrin, Dietary Supplement: Multiple micronutrient powders with 5 mg ironThis 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.
Study group D	Placebo comparator	Dietary Supplement: Multiple micronutrient powders with 5 mg ironThis 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).

Who may qualify

Ages: 21 to 27 weeks
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Galacto-oligosaccharidesGalacto-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.	Dietary supplement	Study group A: GOS, Study group C: GOS + bLF
Bovine lactoferrinBovine 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.	Dietary supplement	Study group B: bLF, Study group C: GOS + bLF
Multiple micronutrient powders with 5 mg ironThe 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].	Dietary supplement	Study group A: GOS, Study group B: bLF, Study group C: GOS + bLF, Study group D

Primary outcome

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

11 secondary outcomes

Ratio of Harmful to Beneficial Bacterial Genera in Fecal Microbiota as Determined by Quantitative Polymerase Chain Reaction (qPCR) at 6 Months
Time frame: 6 months
Ratio of Harmful to Beneficial Bacterial Genera in Fecal Microbiota as Determined by Quantitative Polymerase Chain Reaction (qPCR) at 9 Months
Time frame: 9 months
Microbiota Composition as Determined by Quantitative Polymerase Chain Reaction (qPCR).
Time frame: 1, 6 and 9 months
Number of Participants Who Experienced Diarrhea
Time frame: Up to 9 months
Number of Participants Who Experienced Malaria
Time frame: Up to 9 months
Proportion of Participants Who Experienced Anemia
Time frame: Baseline, 1 month, 6 months, 9 months
Proportion of Participants Who Experienced Iron Deficiency
Time frame: Baseline, 1 month, 6 months, 9 months
Proportion of Participants Who Experienced Iron Deficiency Anemia (IDA)
Time frame: Baseline, 1 month, 6 months, 9 months
Proportion of Participants Who Experienced Inflammation
Time frame: Baseline, 1 month, 6 months, 9 months
Number of Participants Who Experienced Respiratory Tract Infections
Time frame: Up to 9 months
Other Illnesses
Time frame: Up to 9 months

Results and safety

Results posted to the registry on 8 Jan 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Study Group A: MMP + Iron + GOS	72	72
Study Group B: MMP + Iron + bLF	72	72
Study Group C: MMP + Iron + GOS + bLF	72	72
Study Group D: MMP + Iron	72	72

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

Time frame: 1 month. Mean (Standard Error). Unit: (unitless)

Measure	Study Group A: MMP + Iron + GOS n = 70	Study Group B: MMP + Iron + bLF n = 72	Study Group C: MMP + Iron + GOS + bLF n = 70	Study Group D: MMP + Iron n = 70
Value	2.208 (0.202)	1.530 (0.207)	2.075 (0.220)	1.292 (0.176)

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: 9 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Study Group A: GOS	1 of 72 (1.4%)	56 of 72 (77.8%)	0 of 72
Study Group B: bLF	1 of 72 (1.4%)	55 of 72 (76.4%)	0 of 72
Study Group C: GOS + bLF	0 of 72 (0%)	59 of 72 (81.9%)	0 of 72
Study Group D: Iron	1 of 72 (1.4%)	65 of 72 (90.3%)	1 of 72

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25143342Jaeggi T, Kortman GA, Moretti D, Chassard C, Holding P, Dostal A, Boekhorst J, Timmerman HM, Swinkels DW, Tjalsma H, Njenga J, Mwangi A, Kvalsvig J, Lacroix C, Zimmermann MB. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut. 2015 May;64(5):731-42. doi: 10.1136/gutjnl-2014-307720. Epub 2014 Aug 20.
Background: PubMed 27529276Paganini D, Uyoga MA, Zimmermann MB. Iron Fortification of Foods for Infants and Children in Low-Income Countries: Effects on the Gut Microbiome, Gut Inflammation, and Diarrhea. Nutrients. 2016 Aug 12;8(8):494. doi: 10.3390/nu8080494.
Background: PubMed 20962160Zimmermann MB, Chassard C, Rohner F, N'goran EK, Nindjin C, Dostal A, Utzinger J, Ghattas H, Lacroix C, Hurrell RF. The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire. Am J Clin Nutr. 2010 Dec;92(6):1406-15. doi: 10.3945/ajcn.110.004564. Epub 2010 Oct 20.
Background: PubMed 22190022Dostal A, Chassard C, Hilty FM, Zimmermann MB, Jaeggi T, Rossi S, Lacroix C. Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats. J Nutr. 2012 Feb;142(2):271-7. doi: 10.3945/jn.111.148643. Epub 2011 Dec 21.
Background: PubMed 22845175Dostal A, Fehlbaum S, Chassard C, Zimmermann MB, Lacroix C. Low iron availability in continuous in vitro colonic fermentations induces strong dysbiosis of the child gut microbial consortium and a decrease in main metabolites. FEMS Microbiol Ecol. 2013 Jan;83(1):161-75. doi: 10.1111/j.1574-6941.2012.01461.x. Epub 2012 Aug 28.
Background: PubMed 24555487Dostal A, Lacroix C, Pham VT, Zimmermann MB, Del'homme C, Bernalier-Donadille A, Chassard C. Iron supplementation promotes gut microbiota metabolic activity but not colitis markers in human gut microbiota-associated rats. Br J Nutr. 2014 Jun 28;111(12):2135-45. doi: 10.1017/S000711451400021X. Epub 2014 Feb 21.
Background: PubMed 24676135Dostal A, Gagnon M, Chassard C, Zimmermann MB, O'Mahony L, Lacroix C. Salmonella adhesion, invasion and cellular immune responses are differentially affected by iron concentrations in a combined in vitro gut fermentation-cell model. PLoS One. 2014 Mar 27;9(3):e93549. doi: 10.1371/journal.pone.0093549. eCollection 2014.
Background: PubMed 26578675Dostal A, Lacroix C, Bircher L, Pham VT, Follador R, Zimmermann MB, Chassard C. Iron Modulates Butyrate Production by a Child Gut Microbiota In Vitro. mBio. 2015 Nov 17;6(6):e01453-15. doi: 10.1128/mBio.01453-15.
Background: PubMed 25562815Lacroix C, de Wouters T, Chassard C. Integrated multi-scale strategies to investigate nutritional compounds and their effect on the gut microbiota. Curr Opin Biotechnol. 2015 Apr;32:149-155. doi: 10.1016/j.copbio.2014.12.009. Epub 2015 Jan 3.
Background: PubMed 21764163Payne AN, Zihler A, Chassard C, Lacroix C. Advances and perspectives in in vitro human gut fermentation modeling. Trends Biotechnol. 2012 Jan;30(1):17-25. doi: 10.1016/j.tibtech.2011.06.011. Epub 2011 Jul 20.
Background: PubMed 22324938Payne AN, Chassard C, Banz Y, Lacroix C. The composition and metabolic activity of child gut microbiota demonstrate differential adaptation to varied nutrient loads in an in vitro model of colonic fermentation. FEMS Microbiol Ecol. 2012 Jun;80(3):608-23. doi: 10.1111/j.1574-6941.2012.01330.x. Epub 2012 Mar 27.
Background: PubMed 24709947Tanner SA, Zihler Berner A, Rigozzi E, Grattepanche F, Chassard C, Lacroix C. In vitro continuous fermentation model (PolyFermS) of the swine proximal colon for simultaneous testing on the same gut microbiota. PLoS One. 2014 Apr 7;9(4):e94123. doi: 10.1371/journal.pone.0094123. eCollection 2014.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gary M Brittenham, MD principal investigator

Columbia University

2 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Galacto-oligosaccharides, Bovine lactoferrin and Multiple micronutrient powders with 5 mg iron in people with Iron-deficiency, run by Columbia University at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Kenya, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ratio of Harmful to Beneficial Bacterial Genera in Fecal Microbiota as Determined by Quantitative Polymerase Chain Reaction (qPCR) at 1 Month (time frame: 1 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03866837, which also lists 27 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2025.