Rifaximin on Visceral Hypersensitivity

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Rifaximin on Visceral Hypersensitivity in Irritable Bowel Syndrome

Conditions
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Visceral Hypersensitivity, Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: Rifaximin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic<br>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<br>* 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.<br>* Other names: Xifaxan;|

What is the study measuring?
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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. | 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. | 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 ) | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rifaximin, Xifaxan