Rifaximin on Visceral Hypersensitivity

August 18, 2022 updated by: Nipaporn Pichetshote, Cedars-Sinai Medical Center

Effects of Rifaximin on Visceral Hypersensitivity in Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, with a global prevalence of 11% according to a recent meta-analysis. The total cost of managing IBS in the United States is in excess of $30 billion per year, including indirect costs relating to loss of productivity of more than $20 billion. Abdominal pain/discomfort (i.e. visceral hypersensitivity) is present in all patients with IBS and remains the most therapy-resistant symptom. Apart from abdominal pain, which is measured subjectively using visual scales, several studies have shown a significant increase in rectal sensitivity, which is measured objectively using an inflatable balloon. Drugs which are shown to have objective effects on visceral hypersensitivity are crucial in the management of IBS.

While certain drugs have shown to decrease abdominal pain, there is very little data to substantiate objective changes in visceral hypersensitivity. Rifaximin is a poorly absorbed antibiotic and the exact underlying mechanism of action for rifaximin in reducing the pain component of IBS remains unknown. However, rifaximin has been shown in randomized controlled trials to decrease abdominal discomfort in all subtypes of IBS.

The investigators hypothesize that rifaximin is effective in decreasing rectal visceral hypersensitivity in IBS patients. In this study, the investigators propose to test this hypothesis by measuring visceral hypersensitivity using the graded balloon distention test, before and after a course of rifaximin. To test whether this effect is accompanied by treating SIBO, the investigators will also perform lactulose breath tests before and after rifaximin therapy.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female subjects aged 18-75 years old inclusive
  • Meet Rome IV criteria for IBS-D or IBS-M
  • Subjects should report urgency with bowel movement at least once a week
  • If subjects are ≥50 years old, a colonoscopy must have been completed within the past 5 years
  • Subjects are capable of understanding the requirements of the study, are willing to comply with all the study procedures, and are willing to attend all study visits.
  • Agree to use an acceptable method of contraception throughout their participation in the study. Acceptable methods of contraception include: double barrier methods (condom with spermicidal jelly or a diaphragm with spermicide); hormonal methods (e. g. oral contraceptives, patches or medroxyprogesterone acetate); or an intrauterine device (IUD) with a documented failure rate of less than 1% per year. Abstinence or partner(s) with a vasectomy may be considered an acceptable method of contraception at the discretion of the investigator.
  • All subjects will provide Institutional Review Board (IRB)-approved informed written consent prior to beginning any study-related activities

NOTE: Female subjects who have been surgically sterilized (e.g. hysterectomy or bilateral tubal ligation) or who are postmenopausal (total cessation of menses for >1 year) will not be considered "females of childbearing potential".

Exclusion Criteria:

  • Treatment with antibiotics or Xifaxan in the last two months
  • Subjects with history of intestinal surgery (except appendectomy or cholecystectomy)
  • Subjects with known pelvic floor dysfunction
  • Pregnancy
  • Nursing mothers
  • Poorly controlled/uncontrolled significant medical condition that would interfere with study procedures
  • History of bowel obstruction
  • History of celiac disease
  • History of inflammatory bowel disease
  • Cirrhosis
  • IBS-C/chronic idiopathic constipation
  • Diabetes
  • History of anorectal radiation/surgery
  • History of prostatitis
  • Known allergy or hypersensitivity to rifaximin or rifamycin
  • Current treatment with eluxadoline or opiates

NOTE: Development of any of the exclusion criteria during the study will be considered a basis for subject discontinuation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Therapeutic
40 subjects with diarrhea-predominant IBS (IBS-D) or mixed IBS (IBS-M) will be enrolled in the study. At the first clinic visit, subjects will undergo rectal sensitivity testing, as well as lactulose breath testing. Subjects will be asked to record their symptoms and bowel habits in a diary over the next 7 days. During the second clinic visit, subjects will receive a 14-day course of rifaximin (550 mg PO TID). During these 14 days, subjects will record their symptoms and bowel habits. Subjects will return to the clinic after completion of the medication and will undergo repeat evaluation via rectal sensitivity testing to assess for change in rectal sensitivity.
Drug: Rifaximin
Rifaximin will be administered to patients diagnosed with IBS-D or IBS-M to evaluate whether the medication is effective in decreasing rectal hypersensitivity. The secondary objective of the study is to assess the role of SIBO in rectal sensitivity.
Other Names:
  • Xifaxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change in the Balloon Volume (Measured in Cubic Centimeter) That Leads to First Urge to Defecate.
Time Frame: After completing 14-day course of rifaximin.
A 100-cubic centimeter visual analogue scale with verbal descriptors (0=no sensation, 20=first sensation, 40=first sense of urge, 60=normal urge to defecate, 80=severe urge to defecate, and 100=discomfort/pain) will be used to score evoked sensations.
After completing 14-day course of rifaximin.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association of Urgency Symptom and Rectal Sensitivity Testing.
Time Frame: After completing 14-day course of rifaximin.
Association of urgency symptom and rectal sensitivity will be evaluated by the mean change in the balloon pressure (measured in mmHg) that leads to first urge sensation to defecate, evaluated based on the visual analogue scale defined in the primary outcome measure.
After completing 14-day course of rifaximin.
Number of Participants With a Rise of Hydrogen <20 Parts Per Million Within 90 Minutes of Lactulose Ingestion.(Which is Considered Normal )
Time Frame: After completing 14-day course of rifaximin

Normalization of lactulose breath test as a potential predictor of improvement of rectal hypersensitivity will be evaluated by comparing lactulose breath test results pre- and post-treatment.

Normalization of lactulose breath test defined as rise of hydrogen <20 Parts per million within 90 minutes of lactulose ingestion.

patients with positive
After completing 14-day course of rifaximin

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cedars-Sinai Medical Center

Collaborators

Bausch Health Americas, Inc.

Investigators

  • Principal Investigator: Nipaporn Pichetshote, MD, Cedars-Sinai Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2018

Primary Completion (Actual)

November 19, 2021

Study Completion (Actual)

November 19, 2021

Study Registration Dates

First Submitted

November 20, 2017

First Submitted That Met QC Criteria

March 9, 2018

First Posted (Actual)

March 13, 2018

Study Record Updates

Last Update Posted (Actual)

September 13, 2022

Last Update Submitted That Met QC Criteria

August 18, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 49509

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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