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| ID | Type | Description | Link |
|---|---|---|---|
| 1K23DK124567 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Michigan Institute for Clinical and Health Research (MICHR) | UNKNOWN |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rifaximin | Active Comparator | Rifaximin 550 mg three times daily for 14 days |
|
| Low FODMAP Group | Active Comparator | Low FODMAP diet for 4 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rifaximin 550 MG | Drug | Rifaximin 550 mg three times daily for 14 days |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Baseline, Week 5 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Week 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Glucose Breath Tests | Glucose breath tests (GBT) will be performed at baseline and repeated after intervention | 4 weeks |
| Fecal Microbiota | Changes in fecal microbial diversity after intervention will be compared with baseline. |
Inclusion Criteria:
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.
Exclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Allen Lee, MD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42025708 | Derived | Lee A, 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. |
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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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| ID | Title | Description |
|---|---|---|
| FG000 | Rifaximin | Rifaximin 550 mg three times daily for 14 days Rifaximin 550 MG: Rifaximin 550 mg three times daily for 14 days |
| FG001 | Low FODMAP Group | Low FODMAP diet for 4 weeks Low FODMAP Diet: Low FODMAP dietary intervention for 4 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline data was collected for all participants who were randomized to an arm, regardless of whether they received an intervention.
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| ID | Title | Description |
|---|---|---|
| BG000 | Rifaximin | Rifaximin 550 mg three times daily for 14 days Rifaximin 550 MG: Rifaximin 550 mg three times daily for 14 days |
| BG001 | Low FODMAP Group | Low FODMAP diet for 4 weeks Low FODMAP Diet: Low FODMAP dietary intervention for 4 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Some participants who were randomized to an arm withdrew or were lost to follow up before receiving an intervention. The number of participants analyzed at each time point is based on a modified intent to treat (mITT) analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 5 |
|
5 weeks
Some participants who were randomized to an arm withdrew or were lost to follow up before receiving an intervention. The number of participants analyzed is based on a mITT analysis.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rifaximin | Rifaximin 550 mg three times daily for 14 days Rifaximin 550 MG: Rifaximin 550 mg three times daily for 14 days |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness/Light-headedness | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Allen Lee | University of Michigan | 734-936-4785 | allenlee@med.umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 6, 2023 | Jan 9, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 11, 2024 | Mar 18, 2025 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D043183 | Irritable Bowel Syndrome |
| D003967 | Diarrhea |
| ID | Term |
|---|---|
| D003109 | Colonic Diseases, Functional |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
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| ID | Term |
|---|---|
| D000078262 | Rifaximin |
| D000092622 | FODMAP Diet |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Low FODMAP Diet |
| Other |
Low FODMAP dietary intervention for 4 weeks |
|
| 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. | 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. | 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. | 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. | 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. | 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. | Baseline, Week 5 |
| 4 weeks |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body Mass Index (BMI) | BMI is a medical screening tool that measures the ratio of height to weight to estimate the amount of body fat a person has. | Mean | Standard Deviation | kg/m^2 |
|
| Low FODMAP Group |
Low FODMAP diet for 4 weeks Low FODMAP Diet: Low FODMAP dietary intervention for 4 weeks |
|
|
|
| Secondary | 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. | Some participants who were randomized to an arm withdrew or were lost to follow up before receiving an intervention. The number of participants analyzed at each time point is based on a mITT analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 5 |
|
|
|
| Secondary | 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. | Some participants who were randomized to an arm withdrew or were lost to follow up before receiving an intervention. The number of participants analyzed at each time point is based on a mITT analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 5 |
|
|
|
| Secondary | 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. | Some participants who were randomized to an arm withdrew or were lost to follow up before receiving an intervention. The number of participants analyzed at each time point is based on a mITT analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 5 |
|
|
|
| Secondary | 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. | Some participants who were randomized to an arm withdrew or were lost to follow up before receiving an intervention. The number of participants analyzed at each time point is based on a mITT analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 5 |
|
|
|
| Secondary | 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. | Some participants who were randomized to an arm withdrew or were lost to follow up before receiving an intervention. The number of participants analyzed at each time point is based on a mITT analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 5 |
|
|
|
| Secondary | 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. | Some participants who were randomized to an arm withdrew or were lost to follow up before receiving an intervention. The number of participants analyzed at each time point is based on a mITT analysis. | Posted | Mean | Standard Deviation | grams per day | Baseline, Week 5 |
|
|
|
| Other Pre-specified | Glucose Breath Tests | Glucose breath tests (GBT) will be performed at baseline and repeated after intervention | Not Posted | 4 weeks | Participants |
| Other Pre-specified | Fecal Microbiota | Changes in fecal microbial diversity after intervention will be compared with baseline. | Not Posted | 4 weeks | Participants |
| Primary | 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. | Some participants who were randomized to an arm withdrew or were lost to follow up before receiving an intervention. The number of participants analyzed at each time point is based on a mITT analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 5 |
|
|
|
|
| Secondary | 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. | Some participants who were randomized to an arm withdrew or were lost to follow up before receiving an intervention. The number of participants analyzed at each time point is based on a mITT analysis. | Posted | Mean | Standard Deviation | grams per day | Baseline, Week 5 |
|
|
|
| 0 |
| 36 |
| 0 |
| 36 |
| 30 |
| 36 |
| EG001 | Low FODMAP Group | Low FODMAP diet for 4 weeks Low FODMAP Diet: Low FODMAP dietary intervention for 4 weeks | 0 | 29 | 0 | 29 | 26 | 29 |
| Abdominal Pain and cramping | Gastrointestinal disorders | Systematic Assessment |
|
| Bloating and gas | Gastrointestinal disorders | Systematic Assessment |
|
| Heartburn | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment |
|
| Belching | Gastrointestinal disorders | Systematic Assessment |
|
| Increased urination | Renal and urinary disorders | Systematic Assessment |
|
| Easily sunburned | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Swelling | General disorders | Systematic Assessment |
|
| Blurry Vision | Eye disorders | Systematic Assessment |
|
| Mucus in Stool | Gastrointestinal disorders | Systematic Assessment |
|
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| D004066 | Digestive System Diseases |
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D000092724 | Elimination Diets |
| D004032 | Diet |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| 0.58 |
| Superiority |