Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Terminated; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Lovastatin; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00302952

DAIT ARA02

Details and patient eligibility

About

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.

Full description

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 (Experimental or Placebo). There will be four study visits over 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.

Enrollment: 64 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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 rituximab
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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64 participants in 2 patient groups, including a placebo group

Lovastatin

Experimental group

Description:

Participants are randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one 40 mg lovastatin tablet or treatment could be discontinued. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.

Treatment:

Drug: Lovastatin

Placebo

Placebo Comparator group

Description:

Participants are randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.

Treatment:

Drug: Placebo