Irritable Bowel SyndromePhase 4NCT03219528
A Longitudinal Study to Identify IBS Phenotypes Using Fecal Microbiota and Hydrogen Breath Testing
A Phase 4 study testing Rifaximin 550 MG and Low FODMAP Diet in people with Irritable Bowel Syndrome, run by University of Michigan at 1 site in United States.
Trial summary
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a highly prevalent but poorly understood condition with limited treatment options. Current therapies, including a nonabsorbable antibiotic rifaximin or diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP), show efficacy… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Irritable Bowel Syndrome
- What is being tested?
- Rifaximin 550 MG and Low FODMAP Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Feb 2018to 28 Feb 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult subjects greater than or equal to 18 years of age who meet Rome IV criteria for diarrhea-predominant irritable bowel syndrome (IBS-D).
- Prior colonoscopy or sigmoidoscopy within the past 2 years with random colon biopsies to exclude the presence of microscopic colitis.
- IBS medications, including anti-depressants, will be allowed if the dose has been stable for at least 1 month before inclusion. Medications will be carefully tracked to follow any potential confounding issues.
Who cannot join
- Underlying celiac disease, inflammatory bowel disease, or other organic disease that could explain their symptoms.
- Subjects with a history of GI tract surgery, except for cholecystectomy or appendectomy, will also be excluded from the study.
- Women who are pregnant or breastfeeding Antibiotics taken within 3 months prior to enrollment will not be permitted. Subjects on probiotics must discontinue their use at least 1 month prior to enrollment.
- Subjects who have previously received formal dietary education for IBS, including a low FODMAP diet, or previously received antibiotics, including rifaximin, for treatment of IBS-D will be excluded from the study.
Trial locations and contacts
1 site in 1 country.
About this study
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a highly prevalent but poorly understood condition with limited treatment options. Current therapies, including a nonabsorbable antibiotic rifaximin or diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP), show efficacy in 50% or less of patients. In this proposal, participants with IBS-D will be randomized to receive either rifaximin or low FODMAP dietary intervention.
Read the detailed description
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a highly prevalent but poorly understood condition with limited treatment options. Recent evidence has established small intestinal bacterial overgrowth (SIBO) and alterations in fecal microbiota as potential etiologies in the pathogenesis of IBS-D. Current therapies, including a nonabsorbable antibiotic rifaximin or diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP), show efficacy in 50% or less of patients [1-4]. It has been postulated that limited responses to therapies may stem from failure to identify distinct subgroups in IBS-D stratified by gut microbial profiles. In this proposal, participants with IBS-D will be randomized to receive either rifaximin or low FODMAP dietary intervention. The results of fecal microbiota-derived data as well as hydrogen breath tests will then be longitudinally followed to define SIBO. These methods will be used to test the hypotheses that: (i) distinct IBS-D phenotypes can be generated by defining fecal microbial populations as well as delineating the presence or absence of SIBO; and (ii) longitudinal analyses using microbe-derived metrics and SIBO status may relate to response to treatment with rifaximin or low FODMAP dietary intervention.
- Conditions
- Irritable Bowel Syndrome
- Being tested
- Rifaximin 550 MG, Low FODMAP Diet
- Keywords
- Irritable Bowel Syndrome, Diarrhea, Small Intestinal Bacterial Overgrowth, Gut Microbiota
- Medical subject headings
- Irritable Bowel Syndrome, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rifaximin 550 MGDrug
Rifaximin 550 mg three times daily for 14 days
Low FODMAP DietOther
Low FODMAP dietary intervention for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Rifaximin | Active comparator | Rifaximin 550 mg three times daily for 14 days Receives: Drug: Rifaximin 550 MG |
| Low FODMAP Group | Active comparator | Low FODMAP diet for 4 weeks Receives: Other: Low FODMAP Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Mean Daily Abdominal Pain
Change in mean daily abdominal pain was measured using a visual analog scale (VAS) after intervention compared with baseline. VAS was a scale of 0 to 10, with higher numbers indicating a higher degree of pain; 0 indicated no pain and 10 indicated severe pain.
Measured: Baseline, Week 5
Change in Mean Daily Bloating
Change in mean daily bloating was measured using a visual analog scale (VAS) after intervention compared with baseline. VAS was a scale of 0 to 10, with higher numbers indicating a higher degree of bloating; 0 indicated no bloating and 10 indicated severe bloating.
Measured: Baseline, Week 5
Secondary outcomes (7)
Change in Irritable Bowel Syndrome (IBS) Symptom Severity Scale
The IBS Symptom Severity Scale was comprised of 5 questions each of which was on a scale of 0 to 100, with higher scores indicating more severe symptoms. The total range of the scale was 0 to 500, with 0 meaning no IBS symptoms and 500 indicating severe IBS symptoms.
Measured: Baseline, Week 5
Change in Gastrointestinal System Ratings Scale (GSRS)
The GSRS was a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal Pain, Indigestion, Diarrhea, and Constipation. The GSRS had a seven-point graded Likert scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. The total range of the scale is 15 to 105 with 15 meaning low symptom burden and 105 meaning high symptom burden.
Measured: Baseline, Week 5
Change in Stool Form
The Bristol Stool Form Scale was a diagnostic tool used to assess various digestive issues based on the type and shape of stool. The total range of the scale was 1 to 7, with 1 indicating hard stool and 7 indicating liquid stool.
Measured: Baseline, Week 5
Change in Psychological Function
The PHQ-9 was a multipurpose instrument for screening, diagnosing, monitoring, and measuring the severity of depression. It is comprised of 9 questions, each ranging from 0 to 3 with higher values indicating more severe depression symptoms. The total range of the scale was 1 to 27, with 1 indicating no or minimal depression and 27 indicating severe depression.
Measured: Baseline, Week 5
Change in Irritable Bowel Syndrome Quality of Life Instrument (IBS-QOL)
IBS-QOL was a condition-specific instrument for assessing health-related quality of life among persons with IBS. The IBS-QOL was comprised of 34 questions, each with a 5-point scale where the higher the value indicated the higher quality of life. The total range of the scale was 0 to 100, with 0 indicating no quality of life and 100 indicating extremely good quality of life.
Measured: Baseline, Week 5
24-hour Diet Recall/Intake - Lactose
Participants completed entries using the Nutrition Data System for Research (NDSR), which was a Windows-based dietary analysis program designed for the collection and analyses of 24-hour dietary recalls, food records, menus, and recipes. The NDSR was incapable of collecting data on all FODMAP-type foods, aside from lactose and gluten. The results represent data from lactose as a surrogate for all other FODMAP foods.
Measured: Baseline, Week 5
24-hour Diet Recall/Intake - Gluten
Participants completed entries using the Nutrition Data System for Research (NDSR), which was a Windows-based dietary analysis program designed for the collection and analyses of 24-hour dietary recalls, food records, menus, and recipes. The NDSR was incapable of collecting data on all FODMAP-type foods, aside from lactose and gluten. The results represent data from gluten as a surrogate for all other FODMAP foods.
Measured: Baseline, Week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2017
- Study start13 Feb 2018
- Primary completion28 Feb 2024
- Study completion28 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Michigan Institute for Clinical and Health Research (MICHR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Principal investigator, Allen Lee, University of Michigan
- Investigators
- Allen Lee, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03219528
- Sponsor's protocol ID
- HUM129427
- Other IDs
- 1K23DK124567
- Status last verified
- Apr 2025
- First submitted
- 13 Jul 2017
- Last updated
- 27 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: All investigators are aware of and agree to abide by the principles for sharing research resources, as described by NIH in "Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Programs." The data generated in this study will be shared in several ways. Manuscripts will be submitted for publication in high-quality peer-reviewed journals. Findings will also be presented at relevant national meetings, including Digestive Disease Week and Association of Clinical and Translational Science.
Publications
Lee AA, Rao K, Singh P, Fehlman J, Gao J, Takakura W, Lynett A, Haller E, Ball S, Marand A, Liu A, Shah E, Menees S, Punglia R, Nojkov B, Eswaran S, Baker J, Chey WD, Owyang C, Young V, Hasler WL. A Randomized Trial of Rifaximin vs Low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols Diet for Symptom Outcomes and Microbiome Changes in Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2026 Apr 21:S1542-3565(26)00316-2. doi: 10.1016/j.cgh.2026.04.014. Online ahead of print.
PubMed 42025708
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Longitudinal Study to Identify IBS Phenotypes Using Fecal Microbiota and Hydrogen Breath Testing
- ClinicalTrials.gov ID
- NCT03219528
- Acronym / sponsor ID
- HUM129427
- Conditions
- Irritable Bowel Syndrome
- Keywords
- Irritable Bowel Syndrome, Diarrhea, Small Intestinal Bacterial Overgrowth, Gut Microbiota
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Michigan Institute for Clinical and Health Research (MICHR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 13 Feb 2018 (actual)
- Primary completion
- 28 Feb 2024 (actual)
- Study completion
- 28 Feb 2024 (actual)
- First posted
- 17 Jul 2017 (actual)
- Results
- Posted 27 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a highly prevalent but poorly understood condition with limited treatment options. Current therapies, including a nonabsorbable antibiotic rifaximin or diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP), show efficacy in 50% or less of patients. In this proposal, participants with IBS-D will be randomized to receive either rifaximin or low FODMAP dietary intervention.
Detailed description
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a highly prevalent but poorly understood condition with limited treatment options. Recent evidence has established small intestinal bacterial overgrowth (SIBO) and alterations in fecal microbiota as potential etiologies in the pathogenesis of IBS-D. Current therapies, including a nonabsorbable antibiotic rifaximin or diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP), show efficacy in 50% or less of patients [1-4]. It has been postulated that limited responses to therapies may stem from failure to identify distinct subgroups in IBS-D stratified by gut microbial profiles. In this proposal, participants with IBS-D will be randomized to receive either rifaximin or low FODMAP dietary intervention. The results of fecal microbiota-derived data as well as hydrogen breath tests will then be longitudinally followed to define SIBO. These methods will be used to test the hypotheses that: (i) distinct IBS-D phenotypes can be generated by defining fecal microbial populations as well as delineating the presence or absence of SIBO; and (ii) longitudinal analyses using microbe-derived metrics and SIBO status may relate to response to treatment with rifaximin or low FODMAP dietary intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rifaximin | Active comparator | Drug: Rifaximin 550 MGRifaximin 550 mg three times daily for 14 days |
| Low FODMAP Group | Active comparator | Other: Low FODMAP DietLow FODMAP diet for 4 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult subjects greater than or equal to 18 years of age who meet Rome IV criteria for diarrhea-predominant irritable bowel syndrome (IBS-D).
- Prior colonoscopy or sigmoidoscopy within the past 2 years with random colon biopsies to exclude the presence of microscopic colitis.
- IBS medications, including anti-depressants, will be allowed if the dose has been stable for at least 1 month before inclusion. Medications will be carefully tracked to follow any potential confounding issues.
Key exclusion criteria (4 listed)
- Underlying celiac disease, inflammatory bowel disease, or other organic disease that could explain their symptoms.
- Subjects with a history of GI tract surgery, except for cholecystectomy or appendectomy, will also be excluded from the study.
- Women who are pregnant or breastfeeding Antibiotics taken within 3 months prior to enrollment will not be permitted. Subjects on probiotics must discontinue their use at least 1 month prior to enrollment.
- Subjects who have previously received formal dietary education for IBS, including a low FODMAP diet, or previously received antibiotics, including rifaximin, for treatment of IBS-D will be excluded from the study.
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 |
|---|---|---|
| Rifaximin 550 MGRifaximin 550 mg three times daily for 14 days | Drug | Rifaximin |
| Low FODMAP DietLow FODMAP dietary intervention for 4 weeks | Other | Low FODMAP Group |
Primary outcome
Change in Mean Daily Abdominal Pain
Time frame: Baseline, Week 5
Change in mean daily abdominal pain was measured using a visual analog scale (VAS) after intervention compared with baseline. VAS was a scale of 0 to 10, with higher numbers indicating a higher degree of pain; 0 indicated no pain and 10 indicated severe pain.
Change in Mean Daily Bloating
Time frame: Baseline, Week 5
Change in mean daily bloating was measured using a visual analog scale (VAS) after intervention compared with baseline. VAS was a scale of 0 to 10, with higher numbers indicating a higher degree of bloating; 0 indicated no bloating and 10 indicated severe bloating.
7 secondary outcomes
Change in Irritable Bowel Syndrome (IBS) Symptom Severity Scale
Time frame: Baseline, Week 5
Change in Gastrointestinal System Ratings Scale (GSRS)
Time frame: Baseline, Week 5
Change in Stool Form
Time frame: Baseline, Week 5
Change in Psychological Function
Time frame: Baseline, Week 5
Change in Irritable Bowel Syndrome Quality of Life Instrument (IBS-QOL)
Time frame: Baseline, Week 5
24-hour Diet Recall/Intake - Lactose
Time frame: Baseline, Week 5
24-hour Diet Recall/Intake - Gluten
Time frame: Baseline, Week 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42025708Lee AA, Rao K, Singh P, Fehlman J, Gao J, Takakura W, Lynett A, Haller E, Ball S, Marand A, Liu A, Shah E, Menees S, Punglia R, Nojkov B, Eswaran S, Baker J, Chey WD, Owyang C, Young V, Hasler WL. A Randomized Trial of Rifaximin vs Low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols Diet for Symptom Outcomes and Microbiome Changes in Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2026 Apr 21:S1542-3565(26)00316-2. doi: 10.1016/j.cgh.2026.04.014. Online ahead of print.
- Individual participant dataSharing planned: No. All investigators are aware of and agree to abide by the principles for sharing research resources, as described by NIH in "Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Programs." The data generated in this study will be shared in several ways. Manuscripts will be submitted for publication in high-quality peer-reviewed journals. Findings will also be presented at relevant national meetings, including Digestive Disease Week and Association of Clinical and Translational Science.
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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.
Allen Lee, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rifaximin 550 MG and Low FODMAP Diet in people with Irritable Bowel Syndrome, run by University of Michigan at 1 site in United States.
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 3 inclusion and 4 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 27 Apr 2025. 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 United States. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Mean Daily Abdominal Pain (time frame: Baseline, Week 5). The study lists 2 primary outcomes in all. 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 NCT03219528, 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 27 Apr 2025.