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

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



Sponsors


Source

University of Michigan

Oversight Info

Has Dmc

No

Is Fda Regulated Drug

Yes

Is Fda Regulated Device

No

Is Us Export

Yes


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, we will randomize IBS-D patients 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, 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.

Overall Status

Not yet recruiting

Start Date

2017-08-01

Completion Date

2020-02-01

Primary Completion Date

2020-02-01

Phase

Phase 4

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Improvement in Mean Daily Pain and/or Bloating
4 weeks

Secondary Outcome

Measure

Time Frame

IBS Symptom Severity Scale
4 weeks

Enrollment

42

Condition


Intervention

Intervention Type

Drug

Intervention Name


Description

Rifaximin 550 mg three times daily for 14 days

Arm Group Label

Rifaximin


Intervention Type

Other

Intervention Name


Description

Low FODMAP dietary intervention for 4 weeks

Arm Group Label

Low FODMAP Group



Eligibility

Criteria

Inclusion Criteria:

- Adult subjects > or = 18 years of age who meet Rome IV criteria for IBS-D

- Prior colonoscopy or sigmoidoscopy within the past 2 years with random colon biopsies
to exclude the presence of microscopic colitis

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 appendectomy, will also be
excluded from the study.

- 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 or SIBO will be excluded from the study.

Gender

All

Minimum Age

18 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Allen Lee, MD
Principal Investigator
University of Michigan

Overall Contact

Last Name

Allen Lee, MD

Phone

(734) 936-9454

Email



Verification Date

2017-07-01

Lastchanged Date

2017-07-13

Firstreceived Date

2017-07-13

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

University of Michigan

Investigator Full Name

Allen Lee

Investigator Title

Clinical Lecturer


Keywords


Has Expanded Access

No

Condition Browse


Number Of Arms

2

Intervention Browse

Mesh Term

Rifaximin

Rifamycins



Arm Group

Arm Group Label

Rifaximin

Arm Group Type

Active Comparator

Description

Rifaximin 550 mg three times daily for 14 days


Arm Group Label

Low FODMAP Group

Arm Group Type

Active Comparator

Description

Low FODMAP diet for 4 weeks



Firstreceived Results Date

N/A

Reference

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.

PMID

21208106


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.

PMID

27528177


Citation

Böhn L, Störsrud S, Liljebo T, Collin L, Lindfors P, Törnblom H, Simrén 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.

PMID

26255043


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.

PMID

27725652



Other Outcome

Measure

Glucose Hydrogen Breath Tests

Time Frame

4 weeks

Description

Glucose hydrogen breath tests (GHBT) will be performed at baseline and repeated after intervention


Measure

Fecal Microbiota

Time Frame

4 weeks

Description

Changes in fecal microbial diversity after intervention will be compared with baseline.



Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

No masking



ClinicalTrials.gov processed this data on July 17, 2017

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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