GI Effects of Iron in Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency; Microbial Colonization; Iron Deficiency Anemia; Iron Deficiency Anemia Treatment
• Intervention / Treatment: Diagnostic test: Lactulose breath test; Other: Stool sample; Other: Daily Diary; Other: Irritable Bowel syndrome severity scoring system (IBS-SSS) questionnaire; Dietary supplement: Ferrous Sulphate

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M3 4BG
      • The Functional Gut Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Ferrous Sulphate; This is a single arm study, all participants will take Ferrous sulphate 200mg (65mg elemental iron) for 4 weeks (+/- 2 days). Participants will be required to take 2 tablets per day.

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; Other: Daily Diary; Monitoring stool form, consistency and frequency on a daily basis; Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Gut Microbiome analysis via stool samples	Qualitative and Quantitative data for faecal microorganisms at baseline and 4-weeks since commencing iron therapy.	4 weeks

Collaborators and Investigators

• Sponsor: Dr Anthony Hobson
• Collaborators: Anglia Ruskin University
• Investigators: Study Chair: Anthony Hobson, The Functional Gut Clinic

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Actual): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: ferrous sulphate
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease Attributes; Hematologic Diseases; Nutrition Disorders; Anemia, Hypochromic; Iron Metabolism Disorders; Malnutrition; Infections; Communicable Diseases; Anemia, Iron-Deficiency; Anemia; Deficiency Diseases; Gastrointestinal Agents; Lactulose
• Other Study ID Numbers: FGC-20-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Results will be written up and published in journal articles and presented at conferences

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No