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Rifaximin on Visceral Hypersensitivity

Primary Purpose

Visceral Hypersensitivity, Irritable Bowel Syndrome

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Rifaximin

About this trial

This is an interventional treatment trial for Visceral Hypersensitivity focused on measuring Rifaximin, Xifaxan

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Cedars-Sinai Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Therapeutic

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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

Full Information

NCT ID

NCT03462966

First Posted

November 20, 2017

Last Updated

August 18, 2022

Sponsor

Cedars-Sinai Medical Center

Collaborators

Bausch Health Americas, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03462966

Brief Title

Rifaximin on Visceral Hypersensitivity

Official Title

Effects of Rifaximin on Visceral Hypersensitivity in Irritable Bowel Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Terminated

Why Stopped

recruitment challenges

Study Start Date

July 1, 2018 (Actual)

Primary Completion Date

November 19, 2021 (Actual)

Study Completion Date

November 19, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Cedars-Sinai Medical Center

Collaborators

Bausch Health Americas, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Visceral Hypersensitivity, Irritable Bowel Syndrome

Keywords

Rifaximin, Xifaxan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Therapeutic

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Rifaximin

Other Intervention Name(s)

Xifaxan

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

After completing 14-day course of rifaximin.

Secondary Outcome Measure Information:

Title

Association of Urgency Symptom and Rectal Sensitivity Testing.

Description

Time Frame

After completing 14-day course of rifaximin.

Title

Number of Participants With a Rise of Hydrogen <20 Parts Per Million Within 90 Minutes of Lactulose Ingestion.(Which is Considered Normal )

Description

Time Frame

After completing 14-day course of rifaximin

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nipaporn Pichetshote, MD

Organizational Affiliation

Cedars-Sinai Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cedars-Sinai Medical Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90048

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22426087

Citation

Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012 Jul;10(7):712-721.e4. doi: 10.1016/j.cgh.2012.02.029. Epub 2012 Mar 15.

Results Reference

background

PubMed Identifier

15926759

Citation

Cash B, Sullivan S, Barghout V. Total costs of IBS: employer and managed care perspective. Am J Manag Care. 2005 Apr;11(1 Suppl):S7-16.

Results Reference

background

PubMed Identifier

19996983

Citation

Low K, Hwang L, Hua J, Zhu A, Morales W, Pimentel M. A combination of rifaximin and neomycin is most effective in treating irritable bowel syndrome patients with methane on lactulose breath test. J Clin Gastroenterol. 2010 Sep;44(8):547-50. doi: 10.1097/MCG.0b013e3181c64c90.

Results Reference

background

PubMed Identifier

16678561

Citation

Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006 Apr;130(5):1480-91. doi: 10.1053/j.gastro.2005.11.061. Erratum In: Gastroenterology. 2006 Aug;131(2):688.

Results Reference

background

PubMed Identifier

19521341

Citation

American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ, Chey WD, Foxx-Orenstein AE, Schiller LR, Schoenfeld PS, Spiegel BM, Talley NJ, Quigley EM. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009 Jan;104 Suppl 1:S1-35. doi: 10.1038/ajg.2008.122. No abstract available.

Results Reference

background

PubMed Identifier

18325967

Citation

Dalrymple J, Bullock I. Diagnosis and management of irritable bowel syndrome in adults in primary care: summary of NICE guidance. BMJ. 2008 Mar 8;336(7643):556-8. doi: 10.1136/bmj.39484.712616.AD. No abstract available. Erratum In: BMJ. 2015;350:h1216.

Results Reference

background

PubMed Identifier

11151884

Citation

Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol. 2000 Dec;95(12):3503-6. doi: 10.1111/j.1572-0241.2000.03368.x.

Results Reference

background

PubMed Identifier

12591062

Citation

Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003 Feb;98(2):412-9. doi: 10.1111/j.1572-0241.2003.07234.x.

Results Reference

background

PubMed Identifier

16305730

Citation

Lupascu A, Gabrielli M, Lauritano EC, Scarpellini E, Santoliquido A, Cammarota G, Flore R, Tondi P, Pola P, Gasbarrini G, Gasbarrini A. Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in irritable bowel syndrome. Aliment Pharmacol Ther. 2005 Dec;22(11-12):1157-60. doi: 10.1111/j.1365-2036.2005.02690.x.

Results Reference

background

PubMed Identifier

16554709

Citation

Cuoco L, Salvagnini M. Small intestine bacterial overgrowth in irritable bowel syndrome: a retrospective study with rifaximin. Minerva Gastroenterol Dietol. 2006 Mar;52(1):89-95.

Results Reference

background

PubMed Identifier

18217406

Citation

Majewski M, McCallum RW. Results of small intestinal bacterial overgrowth testing in irritable bowel syndrome patients: clinical profiles and effects of antibiotic trial. Adv Med Sci. 2007;52:139-42.

Results Reference

background

PubMed Identifier

8438647

Citation

Toskes PP. Bacterial overgrowth of the gastrointestinal tract. Adv Intern Med. 1993;38:387-407. No abstract available.

Results Reference

background

PubMed Identifier

10235214

Citation

Bouhnik Y, Alain S, Attar A, Flourie B, Raskine L, Sanson-Le Pors MJ, Rambaud JC. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am J Gastroenterol. 1999 May;94(5):1327-31. doi: 10.1111/j.1572-0241.1999.01016.x.

Results Reference

background

PubMed Identifier

20572300

Citation

Bures J, Cyrany J, Kohoutova D, Forstl M, Rejchrt S, Kvetina J, Vorisek V, Kopacova M. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010 Jun 28;16(24):2978-90. doi: 10.3748/wjg.v16.i24.2978.

Results Reference

background

PubMed Identifier

17148502

Citation

Posserud I, Stotzer PO, Bjornsson ES, Abrahamsson H, Simren M. Small intestinal bacterial overgrowth in patients with irritable bowel syndrome. Gut. 2007 Jun;56(6):802-8. doi: 10.1136/gut.2006.108712. Epub 2006 Dec 5.

Results Reference

background

PubMed Identifier

22945316

Citation

Sachdev AH, Pimentel M. Antibiotics for irritable bowel syndrome: rationale and current evidence. Curr Gastroenterol Rep. 2012 Oct;14(5):439-45. doi: 10.1007/s11894-012-0284-2.

Results Reference

background

PubMed Identifier

17761126

Citation

Pimentel M, Lezcano S. Irritable Bowel Syndrome: Bacterial Overgrowth--What's Known and What to Do. Curr Treat Options Gastroenterol. 2007 Aug;10(4):328-37. doi: 10.1007/s11938-007-0076-1.

Results Reference

background

PubMed Identifier

22262197

Citation

Pyleris E, Giamarellos-Bourboulis EJ, Tzivras D, Koussoulas V, Barbatzas C, Pimentel M. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012 May;57(5):1321-9. doi: 10.1007/s10620-012-2033-7. Epub 2012 Jan 20.

Results Reference

background

PubMed Identifier

26558923

Citation

Nee J, Zakari M, Lembo AJ. Current and emerging drug options in the treatment of diarrhea predominant irritable bowel syndrome. Expert Opin Pharmacother. 2015;16(18):2781-92. doi: 10.1517/14656566.2015.1101449. Epub 2015 Nov 11.

Results Reference

background

PubMed Identifier

16832617

Citation

Pimentel M, Chatterjee S, Chow EJ, Park S, Kong Y. Neomycin improves constipation-predominant irritable bowel syndrome in a fashion that is dependent on the presence of methane gas: subanalysis of a double-blind randomized controlled study. Dig Dis Sci. 2006 Aug;51(8):1297-301. doi: 10.1007/s10620-006-9104-6. Epub 2006 Jul 11.

Results Reference

background

PubMed Identifier

16454838

Citation

Sharara AI, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, Elhajj I. A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. Am J Gastroenterol. 2006 Feb;101(2):326-33. doi: 10.1111/j.1572-0241.2006.00458.x.

Results Reference

background

PubMed Identifier

21208106

Citation

Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011 Jan 6;364(1):22-32. doi: 10.1056/NEJMoa1004409.

Results Reference

background

PubMed Identifier

17043337

Citation

Pimentel M, Park S, Mirocha J, Kane SV, Kong Y. The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial. Ann Intern Med. 2006 Oct 17;145(8):557-63. doi: 10.7326/0003-4819-145-8-200610170-00004.

Results Reference

background

PubMed Identifier

22251066

Citation

Cremonini F, Lembo A. Rifaximin for the treatment of irritable bowel syndrome. Expert Opin Pharmacother. 2012 Feb;13(3):433-40. doi: 10.1517/14656566.2012.651458. Epub 2012 Jan 18.

Results Reference

background

PubMed Identifier

10792117

Citation

Di Stefano M, Malservisi S, Veneto G, Ferrieri A, Corazza GR. Rifaximin versus chlortetracycline in the short-term treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2000 May;14(5):551-6. doi: 10.1046/j.1365-2036.2000.00751.x.

Results Reference

background

PubMed Identifier

27144627

Citation

Mearin F, Lacy BE, Chang L, Chey WD, Lembo AJ, Simren M, Spiller R. Bowel Disorders. Gastroenterology. 2016 Feb 18:S0016-5085(16)00222-5. doi: 10.1053/j.gastro.2016.02.031. Online ahead of print.

Results Reference

background

Citation

Rezaie A, Chua KS, Chang C, et al. Mo2026 Methane on Breath Test Predicts Altered Rectal Sensation During High Resolution Anorectal Manometry. Gastroenterology 2017;146:S-721.

Results Reference

background

PubMed Identifier

24189713

Citation

van Wanrooij SJ, Wouters MM, Van Oudenhove L, Vanbrabant W, Mondelaers S, Kollmann P, Kreutz F, Schemann M, Boeckxstaens GE. Sensitivity testing in irritable bowel syndrome with rectal capsaicin stimulations: role of TRPV1 upregulation and sensitization in visceral hypersensitivity? Am J Gastroenterol. 2014 Jan;109(1):99-109. doi: 10.1038/ajg.2013.371. Epub 2013 Nov 5.

Results Reference

background

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Rifaximin on Visceral Hypersensitivity

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