Effects of Atorvastatin on Disease Activity and HDL Cholesterol Function in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This research evaluates the effects of a cholesterol-lowering medication, atorvastatin, on both arthritis activity and the ability of high-density lipoprotein cholesterol (HDL-C, sometimes referred to as good cholesterol) to prevent changes in low-density lipoprotein cholesterol (LDL-C, sometimes referred to as bad cholesterol), which lead to atherosclerosis, or hardening of the arteries. We hypothesize that atorvastatin may improve both joint inflammation and the anti-inflammatory properties of HDL cholesterol.

Detailed Description
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Heart attacks are the leading cause of death in patients with rheumatoid arthritis (RA). Cardiovascular events occur more frequently than would be expected in patients with RA and traditional heart risk factors do not explain this increased risk. Further research is needed to pursue ways of reducing heart disease mortality and improving outcome in patients with RA. There is reason to believe that a class of cholesterol-lowering medications called statins, beneficial in cardiovascular disease prevention, may be able to reduce the irritation of the joints (inflammation) associated with RA. Statins have been shown to reduce manifestations of inflammation in the blood of patients at increased risk for heart disease, and in the process reduce the risk of heart attack, stroke, and sudden death. Some similarities in the nature of both RA and heart disease may suggest potential benefits of statin therapy in both conditions. In addition to inflammation, another factor which may contribute to coronary heart disease (CHD) risk in RA patients is dysfunctional high-density lipoprotein cholesterol (HDL-C, sometimes referred to as good cholesterol). Normally, HDL-C acts to counter a type of damage called oxidation within LDL-C which is a critical step in the development and progression of heart disease. Data from patients with RA and system lupus erythematosus (SLE) suggests that patients with active rheumatic diseases such as RA and SLE may have increased amounts of dysfunctional HDL-C, and therefore they may be at increased risk of heart disease. A blood test developed by Dr. Navab and colleagues at UCLA rapidly assesses this HDL-C function. This study will investigate both the level of HDL-C antioxidant function in patients with active RA as well as whether abnormal HDL function can be improved by statin use in this population. This research also evaluates the effects of atorvastatin on arthritis activity. We hypothesize that atorvastatin may improve both joint inflammation and the anti-inflammatory properties of HDL cholesterol.

Official Title
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Effects of Atorvastatin on Disease Activity and HDL Cholesterol Anti-inflammatory Properties in Patients With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfill American College of Rheumatology (ACR) criteria for RA At least 18 years of age Have RA for at least one year with ongoing active disease (active disease defined as at least two of three: 1) ≥ six tender joints; 2) ≥ three swollen joints; 3) ≥ 45 minutes of morning stiffness) Taking stable doses of disease modifying anti-rheumatic drug (DMARD) therapy for at least 3 months prior to study entry - Exclusion Criteria: Unable to give informed consent Pregnant or lactating Eligible for pharmacologic lipid-lowering therapy per National Cholesterol Treatment Program Adult Treatment Panel III guidelines Using any lipid lowering medication Known hepatic disease Elevated liver transaminase levels within the past two months Previous treatment in the last three months with hydroxychloroquine -

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Atorvastatin<br> <br> |
| Experimental: Atorvastatin<br>Atorvastatin | Drug: Atorvastatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HDL anti-inflammatory properties at 0 and 12 weeks |  | at 0 and 12 weeks | 
| Highly sensitive C-reactive protein (hs-CRP) at 0 and 12 weeks |  | at 0 and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease activity score using a 28 joint count (DAS28) at 0,3,6,12, and 18 weeks |  | at 0,3,6,12, and 18 weeks | 
| Patient and physician global assessments on visual analogue pain scale (VAS; 0-100) at 0,3,6,12, and 18 weeks |  | at 0,3,6,12, and 18 weeks | 
| Swollen and tender joint counts at 0,3,6,12,and 18 weeks |  | at 0,3,6,12, and 18 weeks | 
| Patient pain assessment on VAS (0-100)at 0,3,6,12, and 18 weeks |  | at 0,3,6,12, and 18 weeks | 
| Erythrocyte sedimentation rate(Westergren) at 0,3,6,12, and 18 weeks |  | at 0,3,6,12, and 18 weeks | 
| Cholesterol levels at 0,3,6,12, and 18 weeks |  | at 0,3,6,12, and 18 weeks | 
| Health assessment questionnaire disability index (HAQ-DI) at 0,3,6,12, and 18 weeks |  | at 0,3,6,12, and 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, Atherosclerosis, High density lipoprotein (HDL) cholesterol, Statins, HDL anti-inflammatory properties, Atorvastatin