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

Irritable Bowel Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03219528
• Other study ID #: HUM129427
• Status: Completed
• Phase: Phase 4
• Start date: February 13, 2018
• Est. completion date: February 28, 2024

Study information

• Verified date: April 2024
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 in 50% or less of patients. In this proposal, we will randomize IBS-D patients to receive either rifaximin or low FODMAP dietary intervention.

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, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: February 28, 2024
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Irritable Bowel Syndrome

Intervention

Drug:
• Rifaximin 550 MG
Rifaximin 550 mg three times daily for 14 days

Other:
• Low FODMAP Diet
Low FODMAP dietary intervention for 4 weeks

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Michigan Institute for Clinical and Health Research (MICHR)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Bohn L, Storsrud S, Liljebo T, Collin L, Lindfors P, Tornblom H, Simren M. Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial. Gastroenterology. 2015 Nov;149(6):1399-1407.e2. doi: 10.1053/j.gastro.2015.07.054. Epub 2015 Aug 5. — View Citation

Eswaran SL, Chey WD, Han-Markey T, Ball S, Jackson K. A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D. Am J Gastroenterol. 2016 Dec;111(12):1824-1832. doi: 10.1038/ajg.2016.434. Epub 2016 Oct 11. — View Citation

Lembo A, Pimentel M, Rao SS, Schoenfeld P, Cash B, Weinstock LB, Paterson C, Bortey E, Forbes WP. Repeat Treatment With Rifaximin Is Safe and Effective in Patients With Diarrhea-Predominant Irritable Bowel Syndrome. Gastroenterology. 2016 Dec;151(6):1113-1121. doi: 10.1053/j.gastro.2016.08.003. Epub 2016 Aug 13. — View Citation

Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011 Jan 6;364(1):22-32. doi: 10.1056/NEJMoa1004409. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Glucose Breath Tests	Glucose breath tests (GBT) will be performed at baseline and repeated after intervention	4 weeks
Other	Fecal Microbiota	Changes in fecal microbial diversity after intervention will be compared with baseline.	4 weeks
Primary	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	IBS Symptom Severity Scale	Secondary outcomes will be defined by reduction in IBS Symptom Severity Scale by = 50 compared with baseline.	4 weeks