Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis

NCT ID: NCT00302952

Last Updated: 2022-09-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-06
• Study Completion Date: 2012-04-30

Brief Summary

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.

Detailed 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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Lovastatin

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.

Group Type: EXPERIMENTAL

Lovastatin

Intervention Type: DRUG

Two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion

Interventions

Lovastatin

Two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion

Intervention Type: DRUG

Placebo

Two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion

Intervention Type: DRUG

Other Intervention Names

Altoprev; Mevacor; Mevinolin; Inactive drug (pharmacologically)

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Autoimmunity Centers of Excellence

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cynthia Aranow, MD

Role: STUDY_CHAIR

Feinstein Institute for Medical Research NS-LIJ Health System

Betty Diamond, MD

Role: STUDY_CHAIR

Feinstein Institute for Medical Research NS-LIJ Health System

Locations

University of Alabama

Birmingham, Alabama, United States

University of California, San Francisco

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Justus J. Fiechtner, MD, PLLC

Lansing, Michigan, United States

Feinstein Institute for Medical Research NS-LIJ Health System

Manhasset, New York, United States

University of Rochester

Rochester, New York, United States

Carolina Bone and Joint

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Baylor Research Institute

Dallas, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

Abud-Mendoza C, de la Fuente H, Cuevas-Orta E, Baranda L, Cruz-Rizo J, Gonzalez-Amaro R. Therapy with statins in patients with refractory rheumatic diseases: a preliminary study. Lupus. 2003;12(8):607-11. doi: 10.1191/0961203303lu429oa.

Reference Type: BACKGROUND

PMID: 12945719 (View on PubMed)

McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, Capell HA, Sattar N. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet. 2004 Jun 19;363(9426):2015-21. doi: 10.1016/S0140-6736(04)16449-0.

Reference Type: BACKGROUND

PMID: 15207950 (View on PubMed)

Aranow C, Cush J, Bolster MB, Striebich CC, Dall'era M, Mackay M, Olech E, Frech T, Box J, Keating R, Wasko MC, St Clair W, Kivitz A, Huang W, Ricketts P, Welch B, Callahan S, Spychala M, Boyle K, York K, Keyes-Elstein L, Goldmuntz E, Diamond B, Davidson A. A double-blind, placebo-controlled, phase II, randomized study of lovastatin therapy in the treatment of mildly active rheumatoid arthritis. Rheumatology (Oxford). 2020 Jul 1;59(7):1505-1513. doi: 10.1093/rheumatology/kez471.

Reference Type: RESULT

PMID: 31628482 (View on PubMed)

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

Other Identifiers

DAIT ARA02

Identifier Type: -

Identifier Source: org_study_id