A Trial of Rosiglitazone for Ulcerative Colitis

This study has been completed.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
James Lewis, University of Pennsylvania
ClinicalTrials.gov Identifier:
First received: July 16, 2003
Last updated: December 1, 2014
Last verified: December 2014
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.

Condition Intervention Phase
Ulcerative Colitis
Inflammatory Bowel Disease
Drug: Rosiglitazone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled Trial of Rosiglitazone for Treatment of Ulcerative Colitis

Resource links provided by NLM:

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Improvement of Signs and Symptoms of UC at 12 Weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Mayo score decrease >=2 points adjusted for age and smoking status.

Secondary Outcome Measures:
  • Clinical Remission at 12 Weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Mayo Score <=2 at 12 weeks post intervention

  • Endoscopic Remission at 12 Weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 105
Study Start Date: September 2002
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rosiglitazone
4 mg of rosiglitazone taken twice daily for 12 weeks.
Drug: Rosiglitazone
4mg orally twice daily for 12 weeks
Other Name: Avandia
Placebo Comparator: placebo
Identical in appearance to study drug taken twice daily for 12 weeks.

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

INCLUSION CRITERIA: Participants must meet the following criteria for inclusion in the trial:

  • 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: Participants will be ineligible for participation in the trial if they meet any of the following 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00065065

United States, Georgia
Atlanta Gastroenterology Associates
Atlanta, Georgia, United States, 30342
United States, Illinois
University of Chicago Hospitals
Chicago, Illinois, United States, 60637
United States, Maryland
Metropolitan Gastroenterology Group Practice/Chevy Chase Clinical Research
Chevy Chase, Maryland, United States, 20815
Maryland Digestive Diseases Research
Laurel, Maryland, United States, 20707
Capitol Gastroenterology Consultants
Silver Spring, Maryland, United States, 20901
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
Minnesota Gastroenterology
Plymouth, Minnesota, United States, 55446
United States, New Jersey
Atlantic Gastroenterology Associates
Egg Harbor Twp, New Jersey, United States, 08234
United States, North Carolina
Wake Research Associates
Raleigh, North Carolina, United States, 27612
United States, Ohio
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Avamar Center for Endoscopy
Warren, Ohio, United States, 44484
United States, Pennsylvania
University of Pennsylvania - Presbyterian Medical Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
James Lewis
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Director: James D Lewis, MD, MSCE University of Pennsylvania
  More Information

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: James Lewis, Professor of Medicine and Epidemiology, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00065065     History of Changes
Other Study ID Numbers: ROSIE, R01DK059961
Study First Received: July 16, 2003
Results First Received: July 10, 2014
Last Updated: December 1, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Pennsylvania:

Additional relevant MeSH terms:
Colitis, Ulcerative
Inflammatory Bowel Diseases
Colonic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Pathologic Processes
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2015