Clinical trial NCT03219528: A Longitudinal Study to Identify IBS Phenotypes Using Fecal Microbiota and Hydrogen Breath Testing
Official title: A Longitudinal Study to Identify IBS Phenotypes Using Fecal Microbiota and Hydrogen Breath Testing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Irritable Bowel Syndrome
Keywords: Irritable Bowel Syndrome
Diarrhea
Small Intestinal Bacterial Overgrowth
Gut Microbiota
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Michigan Institute for Clinical and Health Research (MICHR)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2017-07-17
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Mean Daily Abdominal Pain
timeFrame: Baseline, Week 5
measure: Change in Mean Daily Bloating
timeFrame: Baseline, Week 5
Secondary outcomes:
measure: Change in Irritable Bowel Syndrome (IBS) Symptom Severity Scale
timeFrame: Baseline, Week 5
measure: Change in Gastrointestinal System Ratings Scale (GSRS)
timeFrame: Baseline, Week 5
measure: Change in Stool Form
timeFrame: Baseline, Week 5
measure: Change in Psychological Function
timeFrame: Baseline, Week 5
measure: Change in Irritable Bowel Syndrome Quality of Life Instrument (IBS-QOL)
timeFrame: Baseline, Week 5
measure: 24-hour Diet Recall/Intake - Lactose
timeFrame: Baseline, Week 5
measure: 24-hour Diet Recall/Intake - Gluten
timeFrame: Baseline, Week 5
Other outcomes:
measure: Glucose Breath Tests
timeFrame: 4 weeks
measure: Fecal Microbiota
timeFrame: 4 weeks
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Allen Lee, MD
role: PRINCIPAL_INVESTIGATOR
References: