A Trial of Rosiglitazone for Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

A Randomized, Placebo-controlled Trial of Rosiglitazone for Treatment of Ulcerative Colitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00065065
• Other study ID #: ROSIE
• Secondary ID: R01DK059961
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2003
• Last updated: December 14, 2017
• Start date: September 2002
• Est. completion date: January 2008

Study information

• Verified date: December 2017
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Rosiglitazone
4mg orally twice daily for 12 weeks
• Placebo
pill that looks identical to rosiglitazone

Locations

Country	Name	City	State
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Metropolitan Gastroenterology Group Practice/Chevy Chase Clinical Research	Chevy Chase	Maryland
United States	University of Chicago Hospitals	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Atlantic Gastroenterology Associates	Egg Harbor Township	New Jersey
United States	Maryland Digestive Diseases Research	Laurel	Maryland
United States	University of Pennsylvania - Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	Minnesota Gastroenterology	Plymouth	Minnesota
United States	Wake Research Associates	Raleigh	North Carolina
United States	Capitol Gastroenterology Consultants	Silver Spring	Maryland
United States	Avamar Center for Endoscopy	Warren	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
James Lewis	GlaxoSmithKline, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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-controll — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Improvement of Signs and Symptoms of UC at 12 Weeks	Mayo score decrease >=2 points adjusted for age and smoking status.	12 weeks
Secondary	Number of Participants With Clinical Remission at 12 Weeks	Mayo Score <=2 at 12 weeks post intervention	12 weeks
Secondary	Number of Participants With Endoscopic Remission at 12 Weeks		12 weeks