Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis

Condition(s) targeted: Rheumatoid Arthritis

Intervention: Lovastatin (Drug); Lovastatin placebo (Device)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Cynthia Aranow, MD, Study Chair, Affiliation: Feinstein Institute for Medical Research NS-LIJ Health System
Betty Diamond, MD, Study Chair, Affiliation: Feinstein Institute for Medical Research NS-LIJ Health System

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Primary outcome:

Frequency of adverse events and serious adverse events

Change in laboratory parameters

Reduction in mean log C-reactive protein (CRP)

Secondary outcome:

Reduction of disease activity, measured by the disease activity score 28 (DAS28)-CRP

Percentage of patients achieving the American College of Rheumatology 20 (ACR20) response criteria

Change in rheumatoid factor (RF) titer

Change in anti-cyclic citrullinated peptide (CCP) titer

Change in autoreactive B cells and serum cytokines after treatment with lovastatin

Functional effect of lovastatin on mevalonate-dependent and -independent pathways

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. 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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

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

University of Alabama, Birmingham, Alabama 35294, United States; Recruiting
S. Louis Bridges, Jr, MD, PhD, Phone: 205-934-7995, Email: LBridges@uab.edu

University of California, San Francisco, San Francisco, California 94143, United States; Recruiting
Maria Dall'Era, MD, Phone: 415-502-1886, Email: maria.dallera@ucsf.edu

University of Colorado, Aurora, Colorado 80095, United States; Recruiting
Ruth Grosskreuz, Phone: 303-724-7518, Email: Ruth.Grosskreuz@ucdenver.edu

University of Chicago Medical Center, Chicago, Illinois 60637, United States; Recruiting
Elizabeth Yan, Phone: 773-854-5357, Email: eyan@medicine@bsd.uchicago.edu
Richard Keating, MD, Principal Investigator

Justus Fiechtner, MD, PC, Lansing, Michigan 48910, United States; Recruiting
Justus Fiechtner, MD, Phone: 517-272-9727, Email: jfiechtner@pol.net

Feinstein Institute for Medical Research NS-LIJ Health System, Manhasset, New York 11030, United States; Recruiting
Cynthia Aranow, MD, Phone: 516-562-3837, Email: caranow@nshs.edu

University of Rochester, Rochester, New York 14642, United States; Recruiting
R. John Looney, MD, Phone: 585-275-5308, Email: John_Looney@urmc.rochester.edu

Carolina Bone and Joint, Charlotte, North Carolina 29425, United States; Recruiting
Kelry Preston, Phone: 704-541-3055, Ext: 233, Email: kpreston@bonesrus.org
Ashrito Dayal, MD, Principal Investigator

Duke University Medical Center, Durham, North Carolina 27710, United States; Recruiting
Edna Scarlett, Phone: 919-684-6150, Email: scarl001@mc.duke.edu

Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, United States; Recruiting
Angela Genovese, Phone: 405-271-7805, Email: Angela-Genovese@omrf.org
Ewa Olech, MD, Principal Investigator

Altoona Center for Clinical Research, Duncansville, Pennsylvania 16635, United States; Recruiting
Ashli Weyandti, Phone: 814-693-0300, Ext: 154, Email: ashliweyandt1125@yahoo.com
Amber Woomer, Phone: (814) 693-0300, Ext: 156, Email: amberwoomer1125@yahoo.com

Medical University of South Carolina, Charleston, South Carolina 29425, United States; Recruiting
Dana Rosson, Phone: 843-792-2014, Email: rosson@musc.edu

Baylor Research Institute, Dallas, Texas 75231, United States; Recruiting
Joseph Moler, Phone: 214-987-1253, Email: joseph.moler@Baylorhealth.edu
John J Cush, MD, Principal Investigator

University of Utah, Salt Lake City, Utah 84132, United States; Recruiting
Tracy Frech, MD, Phone: 801-581-4333, Email: tracy.frech@hsc.utah.edu

Related publications:

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.

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.

Starting date: August 2006
Last updated: September 16, 2011