Official Title: “A Double Blind, Placebo Controlled, Phase II, Randomized Study of Lovastatin Therapy in the Treatment of Mildly Active Rheumatoid Arthritis”

Rheumatoid arthritis (RA) is the most common inflammatory arthritis and a major health problem. The purpose of this study is to determine the safety and effectiveness of lovastatin for controlling inflammation in mildly active RA.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

RA is characterized by persistent inflammation of peripheral joints, causing pain, stiffness, swelling, and warmth. The inflammation may cause progressive joint damage and destruction, resulting in deformity and loss of function. Both traditional and biologic disease-modifying antirheumatic drugs (DMARDs) have been prescribed for RA patients to control existing inflammatory symptoms and affect long-term prognosis. However, DMARD use is expensive, and the long-term safety of DMARDs is unknown. Lovastatin is an HMG-CoA reductase inhibitor (also known as a statin) used to lower levels of cholesterol and other fats in the blood. The purpose of this study is to examine the safety and efficacy of lovastatin in controlling inflammation in individuals with RA who have mildly active RA disease despite treatment.

Participants will be randomly assigned to one of two study arms. Arm A will receive 80 mg lovastatin daily for 12 weeks; Arm B will receive placebo. There will be four study visits over the 12 weeks. At each visit, a physical exam, vital signs measurement, medication history, a pregnancy test (if applicable), and blood collection will occur. Additional safety blood testing will occur at Week 2. Tender and swollen joint counts and a physician global assessment will occur at study entry and Week 12. Participants will also be asked to complete self-assessments at study entry and Week 12.

Intervention(s) in this Clinical Trial

• Drug: Lovastatin

Primary Measures

• Frequency of adverse events and serious adverse events over the course of the study
• change in laboratory parameters from baseline to Week 12
• reduction in mean log C-reactive protein (CRP) from baseline to Week 12

Secondary Measures

• Reduction of disease activity, measured by the disease activity score 28 (DAS28)-CRP from baseline to Week 12
• percentage of patients achieving the American College of Rheumatology 20 (ACR20) response criteria at Week 12
• change in rheumatoid factor (RF) titer from baseline to Week 12
• change in anti-cyclic citrullinated peptide (CCP) titer from baseline to Week 12
• change in autoreactive B cells and serum cytokines after treatment with lovastatin
• functional effect of lovastatin on mevalonate-dependent and -independent pathways

Inclusion Criteria:

• Diagnosis of RA as defined by 1987 American College of Rheumatology (ACR) criteria
• Functional Class I, II, or III RA as defined by 1987 ACR criteria
• Serum C-reactive protein (CRP) measurement of greater than 5 mg/l
• Mildly active disease with at least one swollen and two tender joints, but no more than six swollen and eight tender joints
• If on corticosteroids, dose must be stable and 10 mg/day prednisone (or equivalent) or less for at least 4 weeks prior to study entry
• If on DMARD, dose must be stable for at least 4 weeks (methotrexate, leflunomide, azathioprine, etanercept, adalimumab, anakinra) or at least 3 months (hydroxychloroquine, gold, or abatacept)
• Willing to use acceptable means of contraception

Exclusion Criteria:

• Serum creatinine level greater than 1.5 mg/dl
• Currently taking a statin or have taken a statin within 12 weeks of study entry
• History of an adverse reaction to a statin
• Active or recent infection within 4 weeks of study entry
• Myositis or an unexplained elevation in creatine phosphokinase (CPK)
• Joint replacement surgery within 60 days of study entry or plan to undergo joint replacement surgery during the course of the study
• Intra-articular cortisone injections within 4 weeks of study entry
• Chronic disorders other than RA affecting the joints, including systemic lupus erythematosus (SLE), psoriatic arthritis, gout, scleroderma, or known reactive arthritis (Reiter's syndrome)
• HIV infection
• Hepatitis B surface antigen positive
• Hepatitis C antibody positive
• Treatment with infliximab within 12 weeks of study entry
• Treatment with ritixumab
• Treatment with medications known to be metabolized by the cytochrome P3A4 pathway.
• More information about this criterion can be found in the protocol.
• Require amiodarone or verapamil
• Investigational drug or treatment during the 4 weeks or seven half-lives prior to study entry
• History of alcohol abuse
• History of liver disease, current liver disease (e.g., hepatitis, cirrhosis), or abnormal liver function (AST or ALT greater than 2 times the upper limit of normal
• [ULN])
• Any condition that, in the opinion of the investigator, may interfere with the study
• Pregnancy or breastfeeding

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Overall Clinical Trial Officials and Contacts

Cynthia Aranow, MD Study Chair Feinstein Institute for Medical Research NS-LIJ Health System  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00302952

Study ID Number: DAIT ARA02

ClinicalTrials.gov Identifier: NCT00302952

Health Authority: United States: Food and Drug Administration