A Trial of Rosiglitazone for Ulcerative Colitis

NCT ID: NCT00065065

Last Updated: 2018-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-09-30
• Study Completion Date: 2008-01-31

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled study evaluating rosiglitazone: 4 mg tablets or placebo tablets administered orally twice daily for 12 weeks. The purpose of the study is to evaluate the efficacy and safety of rosiglitazone in the treatment of mild to moderately active ulcerative colitis. Disease activity will be measured using a standard disease activity index. Calculation of the index requires patients to undergo flexible sigmoidoscopy at the start of the study and at week 12.

Detailed Description

Ulcerative colitis is a disease characterized by inflammation (the changes that happen when tissues in the body are injured) of all or a portion of the large intestine. There is presently no medical cure for ulcerative colitis, although surgical removal of the colon would cure the disease. Ulcerative colitis is generally treated with medications against diarrhea and infection, medications which suppress the immune system (the body system that protects a person against foreign substances) or with surgery.

It is thought that the chronic inflammation associated with ulcerative colitis may be related to the release of certain chemicals produced by the body. Rosiglitazone has been shown to inhibit the production of some of these chemicals. The active component of rosiglitazone has also been shown to improve colitis in animal models of colitis. The purpose of this study is to evaluate the benefit of the drug for ulcerative colitis by comparing it to placebo.

This is a randomized controlled trial of rosiglitazone versus placebo in patients who have failed to respond to 5-ASA therapy. Participants will be randomized to receive either rosiglitazone 4mg bid or placebo bid twice daily for a total of 12 weeks. Disease activity will be measured using the Disease Activity Index (DAI) at visits 3 through 8. Additional outcomes measured will include histological disease activity (visits 3 and 7) and quality of life using the IBDQ (visits 3 through 8). The principle analyses will be an intent-to-treat analysis to examine the efficacy of rosiglitazone at a dose of 4mg twice daily compared to placebo to achieve a partial or complete response. Additionally, the change in NF-κB activation prior to and following therapy with either placebo or rosiglitazone will be examined using immunohistochemistry techniques.

Conditions

Ulcerative Colitis; Inflammatory Bowel Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Rosiglitazone

4 mg of rosiglitazone taken twice daily for 12 weeks.

Group Type: EXPERIMENTAL

Rosiglitazone

Intervention Type: DRUG

4mg orally twice daily for 12 weeks

placebo

Identical in appearance to study drug taken twice daily for 12 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

pill that looks identical to rosiglitazone

Interventions

Rosiglitazone

4mg orally twice daily for 12 weeks

Intervention Type: DRUG

Placebo

pill that looks identical to rosiglitazone

Intervention Type: DRUG

Other Intervention Names

Avandia

Eligibility Criteria

Inclusion Criteria

• Must sign and date the informed consent form
• At least 18 years of age
• Documented diagnosis (endoscopic, surgical or x-ray) of ulcerative colitis (UC)
• Mild to moderate ulcerative colitis indicated by Disease Activity Index score of greater than or equal to 4 and less than or equal to 10
• Unless the patient is intolerant of oral 5-ASA therapy, patient must be treated with a minimum of 2 gm daily of an oral 5-ASA agent for a minimum of 4 weeks during the current exacerbation of ulcerative colitis or immediately prior to study entry
• If treated with oral corticosteroids, dose must not exceed 20 mg per day of Prednisone or equivalent
• If treated with corticosteroids, dose must be stable for 4 weeks prior to study entry and remain on same dose throughout
• If treated with 6-mercaptopurine or azathioprine, must have been on medication for 4 months and a stable dose for 2 months prior to study entry
• If a female of childbearing age, the participant must have a negative serum pregnancy test and have been using a medically approved form of contraceptive birth control for 3 months prior to enrollment. Participants, both male and female, must also be willing to use medically approved contraceptive birth control (at least one barrier method) throughout the study
• If treated with rectal therapy, dose must be stable for 2 weeks prior to study entry and remain on same dose throughout

Exclusion Criteria

• Severe ulcerative colitis indicated by Disease Activity Index score of greater than 10
• Class III or IV congestive heart failure by NYHA classification system
• Allergy to thiazolidinediones
• Presence of any medical condition with an expected survival of less than 1 year
• Participants receiving therapy with cyclosporin, anti-TNF therapy, or methotrexate within the last 2 months of screening
• Positive stool culture for enteric pathogens (salmonella, shigella, and campylobacter), positive C.difficile toxin, or positive stool ova and parasite exam
• Positive proteinuria by urine dipstick
• History of chronic liver disease or baseline liver chemistries greater than the upper limit of normal
• Diabetes mellitus requiring hypoglycemic agents
• Participation in study of experimental therapy within 2 months of first screening visit
• Has any of the following laboratory abnormalities: WBC < 3,000 per uL, Neutrophil < 1,000 cell/cu.mm, Platelets <75,000 per uL, INR > 1.2
• Participant is female and is pregnant or currently breastfeeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

James Lewis

OTHER

Sponsor Role: lead

Responsible Party

James Lewis

Professor of Medicine and Epidemiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

James D Lewis, MD, MSCE

Role: STUDY_DIRECTOR

University of Pennsylvania

Locations

Atlanta Gastroenterology Associates

Atlanta, Georgia, United States

University of Chicago Hospitals

Chicago, Illinois, United States

Metropolitan Gastroenterology Group Practice/Chevy Chase Clinical Research

Chevy Chase, Maryland, United States

Maryland Digestive Diseases Research

Laurel, Maryland, United States

Capitol Gastroenterology Consultants

Silver Spring, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Minnesota Gastroenterology

Plymouth, Minnesota, United States

Atlantic Gastroenterology Associates

Egg Harbor, New Jersey, United States

Wake Research Associates

Raleigh, North Carolina, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Avamar Center for Endoscopy

Warren, Ohio, United States

University of Pennsylvania - Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Countries

United States

References

Lewis JD, Lichtenstein GR, Deren JJ, Sands BE, Hanauer SB, Katz JA, Lashner B, Present DH, Chuai S, Ellenberg JH, Nessel L, Wu GD; Rosiglitazone for Ulcerative Colitis Study Group. Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial. Gastroenterology. 2008 Mar;134(3):688-95. doi: 10.1053/j.gastro.2007.12.012. Epub 2007 Dec 7.

Reference Type: RESULT

PMID: 18325386 (View on PubMed)

Lewis JD, Chuai S, Nessel L, Lichtenstein GR, Aberra FN, Ellenberg JH. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 2008 Dec;14(12):1660-6. doi: 10.1002/ibd.20520.

Reference Type: DERIVED

PMID: 18623174 (View on PubMed)

Other Identifiers

R01DK059961

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ROSIE

Identifier Type: -

Identifier Source: org_study_id