PPAR-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease (RAPPAR)
December 7, 2016 updated by: Mariana Kaplan, University of Michigan
Peroxisome Proliferator-activated Receptor-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease
Patients with rheumatoid arthritis have a significantly higher risk to develop heart attacks and other complications of their blood vessels.
New therapies are needed to prevent this complication.
The purpose of this study is to establish the role of the medication pioglitazone in improving the function of the blood vessels and heart and decreasing the risk of future atherosclerosis development in individuals with rheumatoid arthritis.
As a secondary aim-point, we will evaluate the efficacy of pioglitazone in improving rheumatoid arthritis disease activity and markers of inflammation.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This study will establish the role of pioglitazone in improvement of endothelial function, arterial compliance and disease activity in patients with rheumatoid arthritis. This will be a placebo-controlled, double blind, cross-over trial.
Two of the measures which were initially listed as separate outcome measures: (Decrease in inflammation) and Efficacy of pioglitazone in improving rheumatoid arthritis disease activity and markers of inflammation are now shown as a combined score (DAS-28-CRP). The Risks or Side Effects as an outcome measure would be duplicative of the tables in the adverse event section and therefore were deleted as an outcome measure.
Study Type
Interventional
Enrollment (Actual)
143
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109
- University of Michigan
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
21 years to 100 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Women on adequate contraception if they are of child-bearing age.
- Meet revised ACR criteria for RA.
- Stable doses of DMARDS,biologic agents and or corticosteroids for at least 3 months.
Exclusion Criteria:
- Pregnant or lactating women.
- Current smokers or individuals who smoked in the last 6 months.
- Diagnosis of Diabetes, heart failure, or infection.
- Current diagnosis of malignant disease except for basal cell or squamous cell carcinoma of the skin.
- No active liver disease.
- No cholesterol-lowering medications or oral hypoglycemic agents.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
OTHER: Pioglitazone then placebo
Oral daily pioglitazone 30 mg tablets daily for 2 weeks, followed by 45 mg daily tablets until end of study for 3 months compared to placebo in tablets of equal presentation for 3 months, then crossover after a 2 month washout.
|
daily dose, 30 mg daily for 2 weeks followed by 45 mg daily until completing 3 months unless higher dose not tolerated in which case patient remained at 30 mg daily
Other Names:
Used during nitroglycerin-mediated dilatation vascular function measures in both arms of the study if patient's blood pressure permitted.
One single tablet was used per vascular test performed.
|
|
OTHER: placebo then study drug (pioglitazone)
Oral daily placebo for 3 months compared to pioglitazone for 3 months, then crossover after a 2 month washout.
Similar doses as mentioned above.
|
daily dose, 30 mg daily for 2 weeks followed by 45 mg daily until completing 3 months unless higher dose not tolerated in which case patient remained at 30 mg daily
Other Names:
Used during nitroglycerin-mediated dilatation vascular function measures in both arms of the study if patient's blood pressure permitted.
One single tablet was used per vascular test performed.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia
Time Frame: 8 months
|
This measure represents the percentage change in diameter of brachial artery in response to reactive hyperemia.
The data is presented intentionally and only for the results at the conclusion of the study.
|
8 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Rheumatoid Arthritis Disease Activity
Time Frame: 8 mo
|
Quantification of disease activity using validated assessments (disease activity score on 28 joints (DAS28) and and C-reactive protein ( CRP) (Inflammatory marker) as a combined score (DAS-28CRP)). Mean decrease in DAS-28-CRP score when compared to baseline was measured. The range of DAS-28-CRP is 0-10, with 0 meaning no active disease detected and 10 being the most severe active disease detected by joint count and C-reactive protein levels in blood. |
8 mo
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Mariana J Kaplan, MD, University of Michigan
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Marder W, Khalatbari S, Myles JD, Hench R, Yalavarthi S, Lustig S, Brook R, Kaplan MJ. Interleukin 17 as a novel predictor of vascular function in rheumatoid arthritis. Ann Rheum Dis. 2011 Sep;70(9):1550-5. doi: 10.1136/ard.2010.148031. Epub 2011 Jul 4.
- Zhao W, Berthier CC, Lewis EE, McCune WJ, Kretzler M, Kaplan MJ. The peroxisome-proliferator activated receptor-gamma agonist pioglitazone modulates aberrant T cell responses in systemic lupus erythematosus. Clin Immunol. 2013 Oct;149(1):119-32. doi: 10.1016/j.clim.2013.07.002. Epub 2013 Jul 20.
- Marder W, Khalatbari S, Myles JD, Hench R, Lustig S, Yalavarthi S, Parameswaran A, Brook RD, Kaplan MJ. The peroxisome proliferator activated receptor-gamma pioglitazone improves vascular function and decreases disease activity in patients with rheumatoid arthritis. J Am Heart Assoc. 2013 Nov 19;2(6):e000441. doi: 10.1161/JAHA.113.000441.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2007
Primary Completion (ACTUAL)
October 1, 2012
Study Completion (ACTUAL)
January 1, 2013
Study Registration Dates
First Submitted
November 6, 2007
First Submitted That Met QC Criteria
November 6, 2007
First Posted (ESTIMATE)
November 7, 2007
Study Record Updates
Last Update Posted (ESTIMATE)
February 2, 2017
Last Update Submitted That Met QC Criteria
December 7, 2016
Last Verified
December 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HUM11806
- 5R01HL086553 (NIH)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.