Rifaximin on Visceral Hypersensitivity
Condition: Visceral Hypersensitivity; Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Hypersensitivity; Syndrome
Intervention: Rifaximin
Intervention description: 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.
Intervention MeSH terms: Rifaximin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Rifaximin; Xifaxan

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.
    

Eligibility criteria:

        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.