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

• ClinicalTrials.gov Identifier: NCT00356473
• Recruitment Status: Completed
• First Posted: July 26, 2006
• Last Update Posted: June 22, 2012
• Sponsor: University of California, Los Angeles
• Information provided by: University of California, Los Angeles

Tracking Information

• First Submitted Date: July 25, 2006
• First Posted Date: July 26, 2006
• Last Update Posted Date: June 22, 2012
• Study Start Date: March 2003
• Actual Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 21, 2012)

• HDL anti-inflammatory properties at 0 and 12 weeks [ Time Frame: at 0 and 12 weeks ]
• Highly sensitive C-reactive protein (hs-CRP) at 0 and 12 weeks [ Time Frame: at 0 and 12 weeks ]

Original Primary Outcome Measures (submitted: July 25, 2006)

• HDL anti-inflammatory properties at 0 and 12 weeks
• Highly sensitive C-reactive protein (hs-CRP) at 0 and 12 weeks

Current Secondary Outcome Measures (submitted: June 21, 2012)

• Disease activity score using a 28 joint count (DAS28) at 0,3,6,12, and 18 weeks [ Time Frame: 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 [ Time Frame: at 0,3,6,12, and 18 weeks ]
• Swollen and tender joint counts at 0,3,6,12,and 18 weeks [ Time Frame: at 0,3,6,12, and 18 weeks ]
• Patient pain assessment on VAS (0-100)at 0,3,6,12, and 18 weeks [ Time Frame: at 0,3,6,12, and 18 weeks ]
• Erythrocyte sedimentation rate(Westergren) at 0,3,6,12, and 18 weeks [ Time Frame: at 0,3,6,12, and 18 weeks ]
• Cholesterol levels at 0,3,6,12, and 18 weeks [ Time Frame: at 0,3,6,12, and 18 weeks ]
• Health assessment questionnaire disability index (HAQ-DI) at 0,3,6,12, and 18 weeks [ Time Frame: at 0,3,6,12, and 18 weeks ]

Original Secondary Outcome Measures (submitted: July 25, 2006)

• Disease activity score using a 28 joint count (DAS28) 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
• Swollen and tender joint counts at 0,3,6,12,and 18 weeks
• Patient pain assessment on VAS (0-100)at 0,3,6,12, and 18 weeks
• Erythrocyte sedimentation rate(Westergren) at 0,3,6,12, and 18 weeks
• Cholesterol levels at 0,3,6,12, and 18 weeks
• Health assessment questionnaire disability index (HAQ-DI) at 0,3,6,12, and 18 weeks

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis
• Intervention: Drug: Atorvastatin

Study Arms

• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Atorvastatin
• Experimental: Atorvastatin
  Atorvastatin
  Intervention: Drug: Atorvastatin

• Publications *: Charles-Schoeman C, Khanna D, Furst DE, McMahon M, Reddy ST, Fogelman AM, Paulus HE, Park GS, Gong T, Ansell BJ. Effects of high-dose atorvastatin on antiinflammatory properties of high density lipoprotein in patients with rheumatoid arthritis: a pilot study. J Rheumatol. 2007 Jul;34(7):1459-64. Epub 2007 Jun 1.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 25, 2006): 20
• Original Enrollment: Same as current
• Actual Study Completion Date: September 2005
• Actual Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

-

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT00356473
• Other Study ID Numbers: 02-07-061-02
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: University of California, Los Angeles
• Collaborators: Not Provided

Investigators

• Principal Investigator: Benjamin J Ansell, MD; UCLA David Geffen School of Medicine

• PRS Account: University of California, Los Angeles
• Verification Date: June 2006