Rifaximin on Visceral Hypersensitivity

Phase 2

Terminated

Conditions: Irritable Bowel Syndrome
Visceral Hypersensitivity

Interventions: Drug: Rifaximin

Registration Number: NCT03462966

Lead Sponsor: Cedars-Sinai Medical Center

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Therapeutic	Rifaximin	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	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
Association of Urgency Symptom and Rectal Sensitivity Testing.	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.