A Trial of Rosiglitazone for Ulcerative Colitis

• Sponsor: James Lewis (Other)
• Overall Status: Completed
• CT.gov ID: NCT00065065
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), GlaxoSmithKline (Industry)
• Enrollment: 105
• Locations: 13
• Arms: 2
• Duration (Months): 64
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.1

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
Ulcerative Colitis; Inflammatory Bowel Disease	Drug: Rosiglitazone; Drug: Placebo	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

• Study Type: Interventional
• Actual Enrollment: 105 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-controlled Trial of Rosiglitazone for Treatment of Ulcerative Colitis
• Study Start Date: Sep 1, 2002
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

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: Avandia
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

1. 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

1. Number of Participants With Clinical Remission at 12 Weeks [12 weeks]

   Mayo Score <=2 at 12 weeks post intervention

2. Number of Participants With Endoscopic Remission at 12 Weeks [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• 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

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.

• Responsible Party: James Lewis, Professor of Medicine and Epidemiology, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00065065
• Other Study ID Numbers: ROSIE; R01DK059961
• First Posted: Jul 18, 2003
• Last Update Posted: Jan 16, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by James Lewis, Professor of Medicine and Epidemiology, University of Pennsylvania: Rosiglitazone; Ulcerative; Colitis
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Inflammatory Bowel Diseases; Ulcer; Rosiglitazone

Study Results

Participant Flow

Recruitment Details	Patients were recruited from 15 clinical centers between September 6, 2002 and January 11, 2006.

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

1. Primary Outcome

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

2. Secondary Outcome

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%

3. Secondary Outcome

Title	Number of Participants With Endoscopic Remission at 12 Weeks
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

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

[Not Specified]

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.