A Trial of Rosiglitazone for Ulcerative Colitis
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Rosiglitazone 4 mg of rosiglitazone taken twice daily for 12 weeks. |
Drug: Rosiglitazone
4mg orally twice daily for 12 weeks
Other Names:
|
Placebo Comparator: placebo Identical in appearance to study drug taken twice daily for 12 weeks. |
Drug: Placebo
pill that looks identical to rosiglitazone
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Improvement of Signs and Symptoms of UC at 12 Weeks [12 weeks]
Mayo score decrease >=2 points adjusted for age and smoking status.
Secondary Outcome Measures
- Number of Participants With Clinical Remission at 12 Weeks [12 weeks]
Mayo Score <=2 at 12 weeks post intervention
- Number of Participants With Endoscopic Remission at 12 Weeks [12 weeks]
Eligibility Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Atlanta Gastroenterology Associates | Atlanta | Georgia | United States | 30342 |
2 | University of Chicago Hospitals | Chicago | Illinois | United States | 60637 |
3 | Metropolitan Gastroenterology Group Practice/Chevy Chase Clinical Research | Chevy Chase | Maryland | United States | 20815 |
4 | Maryland Digestive Diseases Research | Laurel | Maryland | United States | 20707 |
5 | Capitol Gastroenterology Consultants | Silver Spring | Maryland | United States | 20901 |
6 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
7 | Minnesota Gastroenterology | Plymouth | Minnesota | United States | 55446 |
8 | Atlantic Gastroenterology Associates | Egg Harbor Township | New Jersey | United States | 08234 |
9 | Wake Research Associates | Raleigh | North Carolina | United States | 27612 |
10 | University Hospitals of Cleveland | Cleveland | Ohio | United States | 44106 |
11 | The Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
12 | Avamar Center for Endoscopy | Warren | Ohio | United States | 44484 |
13 | 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)
- GlaxoSmithKline
Investigators
- Study Director: James D Lewis, MD, MSCE, University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ROSIE
- R01DK059961
Study Results
Participant Flow
Recruitment Details | Patients were recruited from 15 clinical centers between September 6, 2002 and January 11, 2006. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Rosiglitazone | Placebo |
---|---|---|
Arm/Group Description | rosiglitazone (Avandia): 4mg orally twice daily for 12 weeks | Placebo identical to study drug twice daily for 12 weeks |
Period Title: Overall Study | ||
STARTED | 52 | 53 |
COMPLETED | 42 | 33 |
NOT COMPLETED | 10 | 20 |
Baseline Characteristics
Arm/Group Title | Rosiglitazone | Placebo | Total |
---|---|---|---|
Arm/Group Description | rosiglitazone (Avandia): 4mg orally twice daily | Identical in appearance to study drug taken twice a day | Total of all reporting groups |
Overall Participants | 52 | 53 | 105 |
Age (years) [Median (Inter-Quartile Range) ] | |||
Median (Inter-Quartile Range) [years] |
42
|
46
|
43
|
Sex: Female, Male (Count of Participants) | |||
Female |
22
42.3%
|
19
35.8%
|
41
39%
|
Male |
30
57.7%
|
34
64.2%
|
64
61%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
2
3.8%
|
0
0%
|
2
1.9%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
1
1.9%
|
1
1%
|
Black or African American |
2
3.8%
|
2
3.8%
|
4
3.8%
|
White |
48
92.3%
|
50
94.3%
|
98
93.3%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (participants) [Number] | |||
United States |
52
100%
|
53
100%
|
105
100%
|
Outcome Measures
Title | Number of Participants With Improvement of Signs and Symptoms of UC at 12 Weeks |
---|---|
Description | Mayo score decrease >=2 points adjusted for age and smoking status. |
Time Frame | 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Rosiglitazone | Placebo |
---|---|---|
Arm/Group Description | rosiglitazone (Avandia): 4mg orally twice daily | Identical in appearance to study drug taken twice a day |
Measure Participants | 52 | 53 |
Number [participants] |
23
44.2%
|
12
22.6%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Rosiglitazone |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | .005 |
Comments | ||
Method | Regression, Logistic | |
Comments | ||
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 4.0 | |
Confidence Interval |
() 95% 1.5 to 10.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Number of Participants With Clinical Remission at 12 Weeks |
---|---|
Description | Mayo Score <=2 at 12 weeks post intervention |
Time Frame | 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Rosiglitazone | Placebo |
---|---|---|
Arm/Group Description | rosiglitazone (Avandia): 4mg orally twice daily | Identical in appearance to study drug taken twice a day |
Measure Participants | 52 | 53 |
Number [participants] |
9
17.3%
|
1
1.9%
|
Title | Number of Participants With Endoscopic Remission at 12 Weeks |
---|---|
Description | |
Time Frame | 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Rosiglitazone | Placebo |
---|---|---|
Arm/Group Description | 4 mg of rosiglitazone taken twice daily for 12 weeks. Rosiglitazone: 4mg orally twice daily for 12 weeks | Identical in appearance to study drug taken twice daily for 12 weeks. Placebo: pill that looks identical to rosiglitazone |
Measure Participants | 52 | 53 |
Count of Participants [Participants] |
4
7.7%
|
1
1.9%
|
Adverse Events
Time Frame | ||||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Rosiglitazone | Placebo | ||
Arm/Group Description | rosiglitazone (Avandia): 4mg orally twice daily | Identical in appearance to study drug taken twice a day | ||
All Cause Mortality |
||||
Rosiglitazone | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Rosiglitazone | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/52 (1.9%) | 5/53 (9.4%) | ||
Gastrointestinal disorders | ||||
Worsening colitis requiring hospitalization and/or colectomy | 1/52 (1.9%) | 1 | 4/53 (7.5%) | 4 |
Bleeding after sigmoidoscopy biopsy | 0/52 (0%) | 0 | 1/53 (1.9%) | 1 |
Psychiatric disorders | ||||
Depression | 1/52 (1.9%) | 1 | 0/53 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
Rosiglitazone | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 36/52 (69.2%) | 30/53 (56.6%) | ||
Gastrointestinal disorders | ||||
Colitis | 4/52 (7.7%) | 6/53 (11.3%) | ||
Diarrhea | 3/52 (5.8%) | 7/53 (13.2%) | ||
Vomiting | 3/52 (5.8%) | 2/53 (3.8%) | ||
Gastrointestinal - other | 6/52 (11.5%) | 8/53 (15.1%) | ||
Abdominal pain and cramping | 4/52 (7.7%) | 2/53 (3.8%) | ||
General disorders | ||||
Edema | 9/52 (17.3%) | 1/53 (1.9%) | ||
Fatigue | 4/52 (7.7%) | 3/53 (5.7%) | ||
Fever | 3/52 (5.8%) | 2/53 (3.8%) | ||
Constitutional symptoms-other | 5/52 (9.6%) | 3/53 (5.7%) | ||
Chest pain | 3/52 (5.8%) | 1/53 (1.9%) | ||
Pain - other | 6/52 (11.5%) | 6/53 (11.3%) | ||
Infections and infestations | ||||
Infection | 5/52 (9.6%) | 3/53 (5.7%) | ||
Investigations | ||||
Decrease in hemoglobin concentration by 2 g/dL | 4/52 (7.7%) | 4/53 (7.5%) | ||
Musculoskeletal and connective tissue disorders | ||||
Musculoskeletal - other | 5/52 (9.6%) | 1/53 (1.9%) | ||
Arthralgia | 3/52 (5.8%) | 2/53 (3.8%) | ||
Myalgia | 4/52 (7.7%) | 0/53 (0%) | ||
Nervous system disorders | ||||
Headache | 10/52 (19.2%) | 7/53 (13.2%) | ||
Renal and urinary disorders | ||||
Proteinuria | 3/52 (5.8%) | 3/53 (5.7%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 3/52 (5.8%) | 3/53 (5.7%) | ||
Skin and subcutaneous tissue disorders | ||||
Dermatologic skin - other | 1/52 (1.9%) | 3/53 (5.7%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | James D. Lewis, MD, MSCE |
---|---|
Organization | University of Pennsylvania |
Phone | 215-573-5137 |
lewisjd@mail.med.upenn.edu |
- ROSIE
- R01DK059961