Iron-deficiencyNCT05033483
Do Iron Supplements Impact the Gut Microbiome of Women of Reproductive Age?
A study testing Ferrous Fumarate in people with Iron-deficiency and Microbial Colonization, run by South Australian Health and Medical Research Institute at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Iron-deficiency, Microbial Colonization, Anemia
- What is being tested?
- Ferrous Fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 1 siteAustralia
- Study dates
- 31 Aug 2021to 1 Jan 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Able to give informed consent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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).
- Conditions
- Iron-deficiency, Microbial Colonization, Anemia
- Being tested
- Ferrous Fumarate, Placebo
- Keywords
- iron supplements, microbiome, women
- Medical subject headings
- Anemia, Iron-Deficiency, Communicable Diseases, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferrous FumarateDietary supplement
Also called Iron Fumarate, ferro-tab
Gelatin capsule containing 200 mg ferrous fumarate and microcrystalline cellulose
PlaceboDietary supplement
Also called Control
Gelatin capsule containing microcrystalline cellulose
| Study group | Role | What they receive |
|---|---|---|
| Iron Supplement | Experimental | 65.7 mg of iron as ferrous fumarate Receives: Dietary Supplement: Ferrous Fumarate |
| Placebo | Active comparator | 0 mg of iron Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weighted UniFrac dissimilarity score
Measure of microbiota beta-diversity
Measured: 21 days
Secondary outcomes (5)
Bray-Curtis dissimilarity score
Measure of microbiota beta-diversity
Measured: 21 days
Shannon Wiener Diversity
Microbiota alpha-diversity score with adjustment for baseline levels
Measured: 21 days
Faith's phylogenetic diversity
Microbiota alpha-diversity score with adjustment for baseline levels
Measured: 21 days
Taxonomic richness
Microbiota alpha-diversity score with adjustment for baseline levels
Measured: 21 days
Relative abundance of core bacterial taxa
Relative abundance of taxa present in >40% of baseline samples, with adjustment for baseline levels
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2021
- Study start31 Aug 2021
- Primary completion6 Nov 2021
- Study completion1 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Iron-deficiencyStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized, controlled, researcher and participant blinded trial with two parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- South Australian Health and Medical Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Flinders University
- Responsible party
- Sponsor
- Investigators
- Steven Taylor, PhD, Principal investigator, South Australian Health and Medical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05033483
- Sponsor's protocol ID
- Iron Mic
- Status last verified
- Nov 2021
- First submitted
- 13 Aug 2021
- Last updated
- 12 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Outlined below
Publications
Elms L, Hand B, Skubisz M, Best KP, Grzeskowiak LE, Rogers GB, Green TJ, Taylor SL. The Effect of Iron Supplements on the Gut Microbiome of Females of Reproductive Age: A Randomized Controlled Trial. J Nutr. 2024 May;154(5):1582-1587. doi: 10.1016/j.tjnut.2024.03.014. Epub 2024 Mar 21.
PubMed 38521191
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Do Iron Supplements Impact the Gut Microbiome of Women of Reproductive Age?
- ClinicalTrials.gov ID
- NCT05033483
- Acronym / sponsor ID
- Iron Mic
- Conditions
- Iron-deficiency, Microbial Colonization, Anemia
- Keywords
- iron supplements, microbiome, women
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- South Australian Health and Medical Research InstituteUniversity, hospital or other
- Collaborators
- Flinders University
- Study start
- 31 Aug 2021 (actual)
- Primary completion
- 6 Nov 2021 (actual)
- Study completion
- 1 Jan 2022 (actual)
- First posted
- 2 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A randomized, controlled, researcher and participant blinded trial with two parallel groups
| Arm | Type | Receives |
|---|---|---|
| Iron Supplement | Experimental | Dietary Supplement: Ferrous Fumarate65.7 mg of iron as ferrous fumarate |
| Placebo | Active comparator | Dietary Supplement: Placebo0 mg of iron |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Able to give informed consent
Key exclusion criteria (5 listed)
- 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
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 |
|---|---|---|
| Ferrous FumarateAlso: Iron Fumarate, ferro-tabGelatin capsule containing 200 mg ferrous fumarate and microcrystalline cellulose | Dietary supplement | Iron Supplement |
| PlaceboAlso: ControlGelatin capsule containing microcrystalline cellulose | Dietary supplement | Placebo |
Primary outcome
Weighted UniFrac dissimilarity score
Time frame: 21 days
Measure of microbiota beta-diversity
5 secondary outcomes
Bray-Curtis dissimilarity score
Time frame: 21 days
Shannon Wiener Diversity
Time frame: 21 days
Faith's phylogenetic diversity
Time frame: 21 days
Taxonomic richness
Time frame: 21 days
Relative abundance of core bacterial taxa
Time frame: 21 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Derived from this study: PubMed 38521191Elms L, Hand B, Skubisz M, Best KP, Grzeskowiak LE, Rogers GB, Green TJ, Taylor SL. The Effect of Iron Supplements on the Gut Microbiome of Females of Reproductive Age: A Randomized Controlled Trial. J Nutr. 2024 May;154(5):1582-1587. doi: 10.1016/j.tjnut.2024.03.014. Epub 2024 Mar 21.
- Individual participant dataSharing planned: Yes. Outlined below
Related trials for Iron-deficiency
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Recruiting
Iron Absorption From a Nutritional Iron Supplement
Iron Absorption, Iron Deficiencies
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Heart Failure With Preserved Ejection Fraction, Iron Deficiencies
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingPhase 4
The Effects of Low-Dose Versus High-Dose Intravenous IRON Therapy With Ferric DerisomaltOSE in Patients With Chronic Heart Failure and Iron Deficiency
Heart Failure, Iron Deficiency
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.
Steven Taylor, PhD principal investigator
South Australian Health and Medical Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ferrous Fumarate in people with Iron-deficiency and Microbial Colonization, run by South Australian Health and Medical Research Institute at 1 site in Australia.
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 1 inclusion and 5 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 12 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Weighted UniFrac dissimilarity score (time frame: 21 days). 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 NCT05033483, which also lists 1 linked publication.
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 12 Apr 2023.