Clinical trial NCT04705662: GI Effects of Iron in Healthy Volunteers
Official title: Investigating the Effects of Iron on the Gastrointestinal Tract in Health.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Iron Deficiency Anemia Treatment
Microbial Colonization
Iron-deficiency
Iron Deficiency Anemia
Keywords: ferrous sulphate
Lead sponsor: The Functional Gut Clinic
Sponsor class: OTHER
Collaborators: name: Anglia Ruskin University
First posted: 2021-01-12
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Over recent years there has been a lot of research looking at how the bacteria in our gut affects our health. Some medications are known to cause changes in gut bacteria.

Many patients that are prescribed iron report gastrointestinal side effects. This research project aims to see if the cause of the gastrointestinal side effects is due to iron causing changes in the gut bacteria. This can be detected via measuring the levels of hydrogen and methane and other compounds in the breath and stool.

Detailed description: Iron deficiency anaemia is the most common health issue worldwide, with approximately \>1.2 billion people affected. In the UK, iron deficiency anaemia most commonly affects pre-school aged children and women aged 15-49 years. In 2011, an estimated 14% of non-pregnant, and 23% of pregnant women in the UK had iron deficiency anaemia, and 2-5% of male and post-menopausal women were also affected. Whilst compared to other areas of the world IDA has a mild public health significance to the UK, it can be the reason for up-to 13% of referrals to gastroenterologists.

Treating IDA with oral supplements or IV infusions are both effective at restoring bodily iron stores. However, success is often greater in those receiving their iron intravenously, due to frequent non-adherence to oral tablets as a result of their side effects. Gastrointestinal complaints, most commonly constipation, are reported by up to 60% of people that take oral iron supplements. These GI complaints causes up to 50% of patient to not follow their treatment plan, meaning their iron deficiency anaemia persists. However, patients that receive intravenous iron infusions instead do not report these symptoms. This suggests that oral iron has an impact on the GI tract as intravenous iron will bypass the gastrointestinal lumen but the mechanism of this remains uncertain.

To investigate the side effects of oral iron supplements and research a potential mechanism for the cause of iron supplement side effects, this study will require healthy volunteers to take ferrous sulphate for 4 weeks. Pre and post intervention participants will be required to provide a stool sample, complete a breath test and answer questionnaires.

Eligibility criteria: Inclusion Criteria:

1. Participant has provided written informed consent before participating in the study after being given a full description of the study and prior to any study-specific procedures being performed.
2. Participant is a male or non-pregnant female (confirmed by pregnancy test) and is age 18 years to 60 years.
3. Participant can communicate well with the Investigator and to comply with the requirements for the entire study.
4. Participant has capacity to understand written English.
5. Participant has no significant medical diagnosis or current or previous chronic gastrointestinal disease requiring medication or surgery (apart from appendectomy). Participant has no disease that would contraindicate iron supplementation e.g. haemochromatosis.
6. Participant is not on regular prescription medicines unless a stable dose for the past 6-months and duration of the trial.
7. Participant has a body mass index (BMI) of 18.5 - 34.9 kg/m2 (bounds included).
8. Participant agrees to follow pre-test diet for 24 hours before giving test sample.
9. Participant agrees to refrain from strenuous physical activity on the day of the breath test.
10. Participant agrees to refrain from smoking on the day of the breath test.
11. Participant agrees to an overnight fast on the night before the breath test. Food and drink must be withheld until after all breath test samples have been taken.
12. Participant agrees to not take any probiotic for 14 days before the breath test or during the study.
13. Participant has not taken antibiotics for 4-weeks before the start of the study or during the study

Exclusion Criteria:

1. Participant has no significant medical diagnosis or current or previous chronic gastrointestinal disease requiring medication or surgery (apart from appendectomy). Participant has no disease that would contraindicate iron supplementation e.g. haemochromatosis.
2. Participant is pregnant or breast feeding.
3. Participant takes medication known to impact the gut microbiome:

   1. Antibiotics used in the last 4 weeks
   2. Regular use of laxatives or anti-diarrheal medication
4. Participant is taking a regular prescription medication that has a contraindication with oral iron supplementation.
5. Participant has undergone a colonoscopy/sigmoidoscopy in the 1 week prior to enrolment.
6. Participant regularly consumes probiotics, prebiotics, fibre supplements in the 4 weeks prior to enrolment and/or is unwilling to exclude the use of probiotics from the diet during the study period.
7. Participant is involved in this study as an Investigator, sub-Investigator, study coordinator, other study staff, or sponsor member.
8. Participant has had previous abdominal or colorectal surgery except appendectomy or hysterectomy.
9. Participant has had oral iron supplementation of IV iron supplementation in the 12 months prior to enrolment.

Primary outcomes:
measure: Breath methane levels
timeFrame: 4 weeks apart
Secondary outcomes:
measure: Volatile organic compounds (VOC) in breath
timeFrame: 4 weeks apart
measure: Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS)
timeFrame: 4 weeks apart
measure: Stool consistency via the Bristol Stool Chart
timeFrame: 4 weeks apart
measure: Gut Microbiome analysis via stool samples
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: The Functional Gut Clinic
state: Greater Manchester
city: Manchester
country: United Kingdom
facility: The Functional Gut Clinic
state: Greater Manchester
Study officials:
affiliation: The Functional Gut Clinic
name: Anthony Hobson
role: STUDY_CHAIR
References: