Irritable Bowel Syndrome, Visceral Hypersensitivity
Conditions
Keywords
Rifaximin, Xifaxan
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.
Interventions
DRUGRifaximin
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.
Sponsors
Bausch Health Americas, Inc.
Cedars-Sinai Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
Countries
United States
Participant flow
Recruitment details
due to recruitment challenges we decided to terminate the clincal trial
Participants by arm
| Arm | Count |
|---|---|
| Therapeutic 4 subjects with diarrhea-predominant IBS (IBS-D) or mixed IBS (IBS-M) enrolled in the study. At the first clinic visit, subjects did rectal sensitivity testing, as well as lactulose breath testing. Subjects were 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 did repeat evaluation via rectal sensitivity testing to assess for change in rectal sensitivity.
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. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Therapeutic |
|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 14.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
| the mean change in the balloon volume that lead to the first urge to defecate | 28 volume cubic centimeter STANDARD_DEVIATION 17.88 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
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.
Time frame: After completing 14-day course of rifaximin.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic | Mean Change in the Balloon Volume (Measured in Cubic Centimeter) That Leads to First Urge to Defecate. | 37.5 volume cubic centimeter | Standard Deviation 22.17 |
Secondary
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.
Time frame: After completing 14-day course of rifaximin.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic | Association of Urgency Symptom and Rectal Sensitivity Testing. | 106 Millimetre of mercury | Standard Deviation 39.29 |
Secondary
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
Time frame: After completing 14-day course of rifaximin
Population: Of the 4 participants, only 2 subjects had a breath test post treatment which is needed for this secondary outcome. Both subjects had a normal breath test after treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Therapeutic | Number of Participants With a Rise of Hydrogen <20 Parts Per Million Within 90 Minutes of Lactulose Ingestion.(Which is Considered Normal ) | 2 Participants |