PPAR-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease

Phase 3

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
placebo then study drug (pioglitazone)	Sublingual nitroglycerine	Oral daily placebo for 3 months compared to pioglitazone for 3 months, then crossover after a 2 month washout. Similar doses as mentioned above.
Pioglitazone then placebo	pioglitazone	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.
Pioglitazone then placebo	Sublingual nitroglycerine	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.
placebo then study drug (pioglitazone)	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.

Primary Outcome Measures

Name	Time	Method
Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia	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.

Secondary Outcome Measures

Name	Time	Method
Rheumatoid Arthritis Disease Activity	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.