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Do Iron Supplements Impact the Gut Microbiome of Women of Reproductive Age?

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ClinicalTrials.gov Identifier: NCT05033483
Recruitment Status : Active, not recruiting
First Posted : September 2, 2021
Last Update Posted : November 30, 2021
Sponsor:
Collaborator:
Flinders University
Information provided by (Responsible Party):
South Australian Health and Medical Research Institute

Brief Summary:
In this randomised controlled trial the investigators will determine whether taking iron supplements compared to placebo for 21 days alters the bacteria (microbiome) in the large intestine of non-pregnant female participants.

Condition or disease Intervention/treatment Phase
Iron-deficiency Microbial Colonization Anemia Dietary Supplement: Ferrous Fumarate Dietary Supplement: Placebo Not Applicable

Detailed Description:

BACKGROUND: Many women take iron-containing supplements during pregnancy. Indeed, the World Health Organization recommends that all pregnant women in low-income countries take an iron supplement containing 60 mg/day of elemental iron to reduce iron deficiency and iron-deficiency anaemia. However, oral iron has poor bioavailability, less than 10% absorbed with the remainder passing into the large intestine unbound, potentially providing a competitive advantage to iron-dependent opportunistic pathogens in the large intestine.

In a large randomized control trial in children, iron supplementation was shown to promote the growth of pathogenic species (E. coli, S. aureus, and L. monocytogenes) and inhibited the growth of commensal species (Lactobacillus and Bifidobacterium). These pathogens are associated with enteric infections, while the commensals act on the host's immune system to prevent colonization and invasion by pathogens.

It is NOT known if iron supplementation during pregnancy impacts the maternal and infant microbiome and, by extension, how this affects the neonatal risk of infection and immune dysregulation. Vertical transmission of the maternal microbiome to the newborn is a major determinant of infant health. If maternal iron supplementation affects the infant's health, strategies would be required to mitigate this risk.

The investigators require preliminary data to show how oral iron supplementation alters the intestinal microbiome in women. The Investigators will recruit non-pregnant female participants as there is no risk of vertical transmission to an infant in non-pregnant women. The investigators will conduct the study in Australia because there is not a natural abundance of pathogens that could potentially cause harm to the women. Nevertheless, the investigators would expect a shift in the microbiome from non-iron to iron, requiring bacterial species to return to baseline after women stop taking the iron.

HYPOTHESIS: Daily iron supplementation versus placebo for 21 days will alter the stool microbiome composition compared to placebo in non-pregnant female participants of reproductive age.

METHODS: 80 female participants (18-45 y) will be randomized to receive capsules containing iron (65.7 mg of elemental iron as ferrous fumarate) or placebo to take daily for 21 days. Stool samples will be collected at baseline, 21 days, and 42 days (washout).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A randomized, controlled, researcher and participant blinded trial with two parallel groups
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

Supplements were packaged by LifeCare Compounding Pharmacy and labelled by staff not involved in the trial, with 2 colours per treatment group.

The randomisation schedule was prepared by an independent statistician. The schedule allocates women to one of the four colours in the ratio 1:1:1:1 using randomly permuted blocks.

Primary Purpose: Other
Official Title: Do Iron Supplements Impact the Gut Microbiome of Women of Reproductive Age?
Actual Study Start Date : August 31, 2021
Actual Primary Completion Date : November 6, 2021
Estimated Study Completion Date : December 1, 2021


Arm Intervention/treatment
Experimental: Iron Supplement
65.7 mg of iron as ferrous fumarate
Dietary Supplement: Ferrous Fumarate
Gelatin capsule containing 200 mg ferrous fumarate and microcrystalline cellulose
Other Names:
  • Iron Fumarate
  • ferro-tab

Active Comparator: Placebo
0 mg of iron
Dietary Supplement: Placebo
Gelatin capsule containing microcrystalline cellulose
Other Name: Control




Primary Outcome Measures :
  1. Weighted UniFrac dissimilarity score [ Time Frame: 21 days ]
    Measure of microbiota beta-diversity


Secondary Outcome Measures :
  1. Bray-Curtis dissimilarity score [ Time Frame: 21 days ]
    Measure of microbiota beta-diversity

  2. Shannon Wiener Diversity [ Time Frame: 21 days ]
    Microbiota alpha-diversity score with adjustment for baseline levels

  3. Faith's phylogenetic diversity [ Time Frame: 21 days ]
    Microbiota alpha-diversity score with adjustment for baseline levels

  4. Taxonomic richness [ Time Frame: 21 days ]
    Microbiota alpha-diversity score with adjustment for baseline levels

  5. Relative abundance of core bacterial taxa [ Time Frame: 21 days ]
    Relative abundance of taxa present in >40% of baseline samples, with adjustment for baseline levels


Other Outcome Measures:
  1. Weighted UniFrac dissimilarity score [ Time Frame: 42 days (washout) ]
    Measure of microbiota beta-diversity

  2. Shannon-Wiener diversity [ Time Frame: 42 days (washout) ]
    Microbiota alpha-diversity score with adjustment for baseline levels

  3. Bray-Curtis dissimilarity score [ Time Frame: 42 days (washout) ]
    Measure of microbiota beta-diversity

  4. Faith's phylogenetic diversity [ Time Frame: 42 days (washout) ]
    Microbiota alpha-diversity score with adjustment for baseline levels

  5. Taxonomic richness [ Time Frame: 42 days (washout) ]
    Microbiota alpha-diversity score with adjustment for baseline levels

  6. Relative abundance of core bacterial taxa [ Time Frame: 42 days (washout) ]
    Relative abundance of taxa present in >40% of baseline samples, with adjustment for baseline levels



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Able to give informed consent

Exclusion Criteria:

  • Pregnant or breastfeeding.
  • Planning on becoming pregnant
  • Diagnosed with iron deficiency and/or anaemia in the previous three months
  • Taken antibiotics in the past three months
  • Taken iron containing supplements in the past three months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05033483


Locations
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Australia, South Australia
SAHMRI
Adelaide, South Australia, Australia, 5000
Sponsors and Collaborators
South Australian Health and Medical Research Institute
Flinders University
Investigators
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Principal Investigator: Steven Taylor, PhD South Australian Health and Medical Research Institute
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Responsible Party: South Australian Health and Medical Research Institute
ClinicalTrials.gov Identifier: NCT05033483    
Other Study ID Numbers: Iron Mic
First Posted: September 2, 2021    Key Record Dates
Last Update Posted: November 30, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Outlined below
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Following final data analysis and primary publication
Access Criteria: Access to study data may be granted, upon review and approval of the Institutional Review Board, investigators, in accordance with South Australian Health and Medical Research Institute Women and Kids 'Guidelines and Agreement for the use of materials in an ancillary study associated with original clinical trials or cohort studies.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by South Australian Health and Medical Research Institute:
iron supplements
microbiome
women
Additional relevant MeSH terms:
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Communicable Diseases
Infections
Disease Attributes
Pathologic Processes
Ferrous fumarate
Trace Elements
Micronutrients
Physiological Effects of Drugs