PPAR-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Peroxisome Proliferator-activated Receptor-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: pioglitazone
* Drug: Sublingual nitroglycerine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pioglitazone then placebo<br>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. | Drug: pioglitazone<br>* 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<br>* Other names: Actos;Drug: Sublingual nitroglycerine<br>* 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.<br>|
| Other: placebo then study drug (pioglitazone)<br>Oral daily placebo for 3 months compared to pioglitazone for 3 months, then crossover after a 2 month washout. Similar doses as mentioned above. | Drug: pioglitazone<br>* 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<br>* Other names: Actos;Drug: Sublingual nitroglycerine<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia | 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 | 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 |