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

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.

Study Overview

• Status: Recruiting
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Drug: Rifaximin 550 MG; Other: Low FODMAP Diet

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, 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.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Allen Lee, MD; Phone Number: (734) 936-9454; Email: allenlee@umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Deepa Chandhrasekhar
      • Contact: Amy Liu
      • Principal Investigator: Allen Lee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	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.	4 weeks

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Michigan Institute for Clinical and Health Research (MICHR)
• Investigators: Principal Investigator: Allen Lee, MD, University of Michigan

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2018
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: July 13, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Irritable Bowel Syndrome; Diarrhea; Gut Microbiota; Small Intestinal Bacterial Overgrowth
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Irritable Bowel Syndrome; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: HUM129427

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes