A Longitudinal Study to Identify IBS Phenotypes Using Fecal Microbiota and Hydrogen Breath Testing

Study Overview
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Brief Summary
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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, we will randomize IBS-D patients to receive either rifaximin or low FODMAP dietary intervention.

Detailed Description
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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, we will randomize IBS-D patients to receive either rifaximin or low FODMAP dietary intervention. We will then longitudinally follow the results of fecal microbiota-derived data as well as hydrogen breath tests to define SIBO. We will use these methods 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.

Official Title
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A Longitudinal Study to Identify IBS Phenotypes Using Fecal Microbiota and Hydrogen Breath Testing

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: Rifaximin 550 MG
* Other: Low FODMAP Diet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rifaximin<br>Rifaximin 550 mg three times daily for 14 days | Drug: Rifaximin 550 MG<br>* Rifaximin 550 mg three times daily for 14 days<br>|
| Active Comparator: Low FODMAP Group<br>Low FODMAP diet for 4 weeks | Other: Low FODMAP Diet<br>* Low FODMAP dietary intervention for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in Mean Daily Pain and/or Bloating | The primary outcome will be changes in mean daily pain or bloating by visual analog scale (VAS) after intervention compared with baseline. Responders to intervention will be defined by ≥ 30% reductions in mean daily pain or bloating by VAS compared with baseline. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IBS Symptom Severity Scale | Secondary outcomes will be defined by reduction in IBS Symptom Severity Scale by ≥ 50 compared with baseline. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Irritable Bowel Syndrome, Diarrhea, Small Intestinal Bacterial Overgrowth, Gut Microbiota