Help guide our efforts to modernize
Send us your comments by March 14, 2020. Menu

Induction of Clinical Response Using Rifaximin in Crohn's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00603616
Recruitment Status : Active, not recruiting
First Posted : January 29, 2008
Last Update Posted : December 7, 2018
Bausch Health Americas, Inc.
Information provided by (Responsible Party):
Scott Lee, University of Washington

Brief Summary:

Antibiotics have been used to treat Crohn's disease symptoms with the best studied antibiotics being Cipro and Flagyl. Rifaximin is a poorly absorbed oral antibiotic that is FDA approved for travelers' diarrhea. It works by inhibiting bacterial reproduction. It is very poorly absorbed and over 97% of the drug taken orally is excreted in the feces.

The purpose of this study is to evaluate the potential benefits and safety of Rifaximin for the treatment of moderate to severe symptoms of Crohn's Disease.

Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: Placebo Comparator Drug: Rifaximin Phase 2

Detailed Description:

Inflammatory bowel disease (IBD) is a debilitating chronic inflammatory disease conventionally categorized into Crohn's disease (CD) and Ulcerative Colitis (UC). CD affects nearly 630,000 people in North America with up to 50,000 new people being diagnosed every year. It is a chronic debilitating disease characterized by abdominal pain, malnutrition, bloody diarrhea, fistula formation, intestinal perforations and strictures, and even extra-intestinal manifestations such as joint pains and skin rashes. Nearly 80% of people with CD will need surgical treatment at some point in their disease process. The majority of CD subjects are diagnosed in young adulthood thereby subjecting them to many decades of discomfort and medical intervention.

Antibiotics have been used to treat CD with variable response rates. The basis for antibiotic therapy is that breakdown of the integrity of the mucosal barrier in the gastrointestinal (GI) tract leads to a heightened inflammatory response to commensurate luminal bacteria. By changing the composition or bacterial load in the intestinal lumen, it may be possible to alter the immune response. Ciprofloxacin (Cipro) and metronidazole (Flagyl) are the best studied antibiotics that have shown efficacy, but the effect is temporal and long term use can lead to serious side effects. Rifaximin is a recent FDA approved antibiotic with broad spectrum of activity, excellent safety profile, and minimal absorption from the GI tract. Open label and small studies in IBD subjects show response rates up to 80% in CD subjects. These studies were limited however in that they were not randomized placebo controlled trials.

The investigators propose to conduct a randomized placebo controlled crossover trial of rifaximin in CD subjects to assess initial clinical response compared to placebo.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Prospective, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Safety and Efficacy of Rifaximin for the Treatment of Moderate to Severe Crohn's Disease
Study Start Date : November 2008
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
Drug Information available for: Rifaximin

Arm Intervention/treatment
Placebo Comparator: 1
Placebo pills
Drug: Placebo Comparator
Matching oral placebo pills to be taken twice daily for a total of 8 weeks

Active Comparator: 2
Drug: Rifaximin
Oral rifaximin 550mg to be taken twice daily for a total of 8 weeks
Other Name: Xifaxan

Primary Outcome Measures :
  1. Evaluate the efficacy of rifaximin 550 mg bid compared to placebo in achieving clinical response in moderate to severe Crohn's Disease (CD) subjects as determined by a > 100 point decrease in the Crohn's Disease Activity Index (CDAI) [ Time Frame: 8 weeks ]

Secondary Outcome Measures :
  1. Evaluate the efficacy of rifaximin compared to placebo at inducing clinical remission in CD subjects [ Time Frame: 8 weeks ]
  2. Evaluate the safety profile of rifaximin in subjects with active CD [ Time Frame: 16 weeks for those subjects who do not cross over, 32 weeks for those who do cross over ]
  3. Evaluate the effect rifaximin has on the quality of life in subjects with CD compared to placebo [ Time Frame: 8 weeks ]
  4. Evaluate if there are any clinical parameters which might predict response to rifaximin [ Time Frame: 8 weeks ]
  5. Compare mean changes in CDAI scores between rifaximin and placebo treated subjects [ Time Frame: 8 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male or female subjects, 18 to 80 years of age, inclusive, that can themselves provide written, informed consent and authorization of use of protected health information prior to any study-related procedures and who are, in the opinion of the investigator(s), likely to comply with all the requirements of the study
  • Subjects must have a prior diagnosis of CD established by endoscopy and clinical parameters as determined by the investigator(s) for at least 3 months prior to randomization
  • Subjects must be able to participate in all required follow-up visits and fill out all related documentation (e.g. symptom diary)
  • Subjects currently with moderately active disease defined as a CDAI 250-450
  • Concomitant medications:

    • If subjects are taking sulfasalazine or 5-ASA products prior to entry, the dose must be stable for at least 4 weeks prior to the randomization
    • If subjects are on azathioprine, 6-mercaptopurine, or methotrexate, they will have had to be on a stable dosage for at least 8 weeks
    • Subjects are allowed to be on corticosteroids at a dose equivalent to 20 mg or less of prednisone, IF the dose has been stable for a minimum of 2 weeks. Steroids must be held stable throughout the induction portion of the study. The maximum dose of budesonide must not exceed 9mg per day and must also have been stable for a minimum of 2 weeks.
    • No oral or intravenous antibiotics within 4 weeks prior to randomization
    • No current or past use of biological treatment within 6 weeks of randomization into study (e.g. infliximab)
    • If subjects have previously been on any of the above products but are no longer taking them, they should not have received any of the relevant therapeutic products within 4 weeks prior to randomization
    • No other experimental or non-FDA approved medications are allowed. If the subject has previously been on an experimental therapy, they must have not received the therapy within the prior 8 weeks prior to randomization
    • Subjects on concomitant medications for CD will not be allowed to change dosages during the study
  • If subjects are at increased risk of colorectal cancer (defined as having an 8-year history of pan-colitis or 12 year history of left sided colitis), they will need to have undergone a colonoscopy with pan-colonic surveillance biopsies within 2 years of the screening visit. The biopsies must be negative for dysplasia
  • Female or male subjects who are surgically sterilized or who are prepared to and agree to practice a double-barrier form of birth control from the screening visit through 30 days (females) and 30 days (males), respectively, from the last dose of study medication. Females who are more than 12 months post-menopausal are also eligible to participate in the study

Exclusion Criteria:

  • Evidence of active infection which may include any of the following

    • Febrile ( > 38.5ºC)
    • Positive blood culture within 2 weeks prior to randomization
    • Evidence of toxic megacolon or abscess
    • Positive stool culture for enteric pathogens, pathogenic ova or parasite, or a positive assay for C. difficile toxin at screening
  • Subjects with CDAI > 450
  • Any current use or use within the last 8 weeks of an investigational drug
  • Current or past use (within past 12 wks) of biological treatment
  • Current or use within the last 4 weeks of any oral or intravenous antibiotic
  • Anticipated increased dosage of any medication to treat CD
  • Anticipated need for surgery within 12 weeks
  • Known obstructive diseases of the gastrointestinal system
  • Medical conditions requiring in-patient hospitalization
  • Proctocolectomy, total colectomy, ileostomy, or stoma
  • Severe cardiopulmonary disease:

    • Congestive heart failure (NYHA Class III or IV)
    • Severe cardiovascular or peripheral vascular disease
    • Myocardial infarction, percutaneous coronary intervention, or bypass surgery within the past 6 months
  • Significant liver disease:

    • Levels of SGOT [AST], SGPT [ALT], or alkaline phosphatase > 2.5x the upper limit of the normal range for the laboratory performing test
    • History of cirrhosis
  • Renal insufficiency, defined as serum creatinine > 150% of the upper limit of the normal range for the laboratory performing the test
  • Abnormal hematology parameters defined as severe anemia with hemoglobin < 8.5 g/dL and/or white blood cell count of < 3,500/ul
  • Malignancy within the past 2 years other than surgically cured skin carcinoma or cervical dysplasia (CIN I-II)
  • History of dysplasia or carcinoma of the colon
  • Pregnant, lactating, or planning to become pregnant during the course of the investigational study
  • Known history of allergic reaction to rifaximin or allergy to any of the rifamycin antimicrobial agents (which include rifampin, rifabutin, and rifapentine)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00603616

Layout table for location information
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Scott Lee
Bausch Health Americas, Inc.
Layout table for investigator information
Principal Investigator: Scott D Lee, MD University of Washington

Layout table for additonal information
Responsible Party: Scott Lee, Professor, University of Washington Identifier: NCT00603616    
Other Study ID Numbers: 32871
32871 ( Other Identifier: University of Washington )
First Posted: January 29, 2008    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Scott Lee, University of Washington:
Inflammatory Bowel Disease
Crohn disease
Crohn's disease
Additional relevant MeSH terms:
Layout table for MeSH terms
Crohn Disease
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Gastrointestinal Agents