Rifaximin on Visceral Hypersensitivity

NCT03462966 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 49509
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Visceral Hypersensitivity; Irritable Bowel Syndrome

Keywords

Rifaximin; Xifaxan

Outcome Measures

Primary Outcomes (1)

• Mean Change in the Balloon Volume (Measured in Cubic Centimeter) That Leads to First Urge to Defecate.

  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 Outcomes (2)

• Association of Urgency Symptom and Rectal Sensitivity Testing.

  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 )

  After completing 14-day course of rifaximin

Study Arms (1)

Therapeutic

EXPERIMENTAL

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

Interventions

Rifaximin DRUG

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.

Also known as: Xifaxan

Therapeutic

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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".

You may not qualify if:

• 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

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Bausch Health Americas, Inc.: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (28)

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  BACKGROUND

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MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Rifaximin

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

recruitment challenges and the COVID pandemic affected our enrollment as we were only able to enroll 4 participants and not all of them finished the outcome measures.

Results Point of Contact

• Title: Mohamad Rashid
• Organization: Cedars-Sinai medical center

mohamad.rashid@cshs.org

310-423-0617

Study Officials

• Nipaporn Pichetshote, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: March 13, 2018
• Study Start: July 1, 2018
• Primary Completion: November 19, 2021
• Study Completion: November 19, 2021
• Last Updated: September 13, 2022
• Results First Posted: September 13, 2022

Record last verified: 2022-08

Locations

US (1)