Clinical trial NCT00554853: PPAR-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease
Official title: Peroxisome Proliferator-activated Receptor-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-11-07
Enrollment: 143
Sex: ALL
Minimum age (years): 21
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia
timeFrame: 8 months
Secondary outcomes:
measure: Rheumatoid Arthritis Disease Activity
timeFrame: 8 mo
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Mariana J Kaplan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.