Clinical trial NCT00065065: A Trial of Rosiglitazone for Ulcerative Colitis
Official title: A Randomized, Placebo-controlled Trial of Rosiglitazone for Treatment of Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Inflammatory Bowel Disease
Keywords: Rosiglitazone
Ulcerative
Colitis
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: GlaxoSmithKline
First posted: 2003-07-18
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Improvement of Signs and Symptoms of UC at 12 Weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of Participants With Clinical Remission at 12 Weeks
timeFrame: 12 weeks
measure: Number of Participants With Endoscopic Remission at 12 Weeks
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: Chevy Chase
country: United States
facility: Metropolitan Gastroenterology Group Practice/Chevy Chase Clinical Research
state: Maryland
city: Laurel
country: United States
facility: Maryland Digestive Diseases Research
state: Maryland
city: Silver Spring
country: United States
facility: Capitol Gastroenterology Consultants
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Plymouth
country: United States
facility: Minnesota Gastroenterology
state: Minnesota
city: Egg Harbor Township
country: United States
facility: Atlantic Gastroenterology Associates
state: New Jersey
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Warren
country: United States
facility: Avamar Center for Endoscopy
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania - Presbyterian Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: James D Lewis, MD, MSCE
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.