Rifaximin on Visceral Hypersensitivity

NCT ID: NCT03462966

Last Updated: 2022-09-13

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-01

Study Completion Date

2021-11-19

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Visceral Hypersensitivity Irritable Bowel Syndrome

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Therapeutic

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.

Group Type EXPERIMENTAL

Rifaximin

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Xifaxan

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Bausch Health Americas, Inc.

INDUSTRY

Sponsor Role collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Nipaporn Pichetshote

Staff Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Nipaporn Pichetshote, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 22426087 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15926759 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19996983 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16678561 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19521341 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18325967 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11151884 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12591062 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16305730 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16554709 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18217406 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 8438647 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10235214 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20572300 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17148502 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22945316 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17761126 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22262197 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26558923 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16832617 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16454838 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21208106 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17043337 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22251066 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10792117 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27144627 (View on PubMed)

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.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 24189713 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

49509

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Rifaximin for Functional Dyspepsia
NCT01643083 COMPLETED PHASE2/PHASE3
Ethosuximide to Treat IBS
NCT02973542 UNKNOWN PHASE2
Efficacy and Safety of SYN-010 in IBS-C
NCT03763175 TERMINATED PHASE2
Probiotics in Irritable Bowel Syndrome
NCT00846170 WITHDRAWN PHASE3