GI Effects of Iron in Healthy Volunteers

Iron Deficiency Anemia Clinical Trial

Official title:

Investigating the Effects of Iron on the Gastrointestinal Tract in Health.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04705662
• Other study ID #: FGC-20-002
• Status: Completed
• Phase: N/A
• Start date: March 1, 2021
• Est. completion date: June 30, 2022

Study information

• Verified date: October 2022
• Source: The Functional Gut Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Communicable Diseases
• Deficiency Diseases
• Infections
• Iron Deficiency Anemia
• Iron Deficiency Anemia Treatment
• Iron-deficiency
• Microbial Colonization

Intervention

Diagnostic Test:
• Lactulose breath test
Participants will complete a 3 hour breath test pre and post iron supplementation. This will include taking 4 exploratory samples for volatile organic compound (VOC) analysis.

Other:
• Stool sample
Participants will provide a stool sample pre and post iron supplementation
• Daily Diary
Monitoring stool form, consistency and frequency on a daily basis
• Irritable Bowel syndrome severity scoring system (IBS-SSS) questionnaire
Participants will complete the questionnaire pre and post iron supplementation

Dietary Supplement:
• Ferrous Sulphate
Participants will take Ferrous sulphate 200mg (65mg elemental iron) for 4 weeks (+/- 2 days). Participants will be required to take 2 tablets per day.

Locations

Country	Name	City	State
United Kingdom	The Functional Gut Clinic	Manchester	Greater Manchester

Sponsors (2)

Lead Sponsor	Collaborator
Dr Anthony Hobson	Anglia Ruskin University

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Breath methane levels	Difference in methane levels in breath samples from baseline and 4-weeks since commencing iron therapy. This will be measured in parts per million (ppm).	4 weeks apart
Secondary	Volatile organic compounds (VOC) in breath	Difference in any breath gas markers. This is exploratory so will look to see what is present at baseline and see how it changes over the 4 week study period.	4 weeks apart
Secondary	Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS)	Comparison in change of IBS-SSS score from baseline to 4 weeks since commencing iron therapy. The minimum score is 0 and maximum score is 500. The greater the score, the worse the severity and frequency of symptoms of abdominal pain and distention, and increased dissatisfaction of overall bowel functioning.	4 weeks apart
Secondary	Stool consistency via the Bristol Stool Chart	Change in stool frequency and form according to the bristol stool chart scale from baseline to 4 weeks since commencing iron therapy.	4 weeks apart
Secondary	Gut Microbiome analysis via stool samples	Qualitative and Quantitative data for faecal microorganisms at baseline and 4-weeks since commencing iron therapy.	4 weeks