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Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis
This study is currently recruiting participants.
Verified by National Institute of Allergy and Infectious Diseases (NIAID), September 2008
First Received: March 13, 2006   Last Updated: May 5, 2009   History of Changes
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Autoimmunity Centers of Excellence
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00302952
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Lovastatin
Device: Lovastatin placebo
Phase II

MedlinePlus related topics: Rheumatoid Arthritis
Drug Information available for: Lovastatin
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Double Blind, Placebo Controlled, Phase II, Randomized Study of Lovastatin Therapy in the Treatment of Mildly Active Rheumatoid Arthritis

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Frequency of adverse events and serious adverse events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Change in laboratory parameters [ Time Frame: Through Week 12 ] [ Designated as safety issue: No ]
  • Reduction in mean log C-reactive protein (CRP) [ Time Frame: Through Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Reduction of disease activity, measured by the disease activity score 28 (DAS28)-CRP [ Time Frame: Through Week 12 ] [ Designated as safety issue: No ]
  • Percentage of patients achieving the American College of Rheumatology 20 (ACR20) response criteria [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
  • Change in rheumatoid factor (RF) titer [ Time Frame: Through Week 12 ] [ Designated as safety issue: No ]
  • Change in anti-cyclic citrullinated peptide (CCP) titer [ Time Frame: Through Week 12 ] [ Designated as safety issue: No ]
  • Change in autoreactive B cells and serum cytokines after treatment with lovastatin [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Functional effect of lovastatin on mevalonate-dependent and -independent pathways [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: August 2006
Estimated Study Completion Date: August 2010
Estimated Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Participants will receive lovastatin daily for 12 weeks
Drug: Lovastatin
80 mg oral tablet taken daily
2: Placebo Comparator
Participants will receive lovastatin placebo daily for 12 weeks
Device: Lovastatin placebo
Oral placebo tablet taken daily

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00302952

Locations
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35294
Contact: S. Louis Bridges, Jr, MD, PhD     205-934-7995     LBridges@uab.edu    
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Maria Dall'Era, MD     415-502-1886     maria.dallera@ucsf.edu    
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80095
Contact: Jann Wagner     303-724-7516     Janice.Wagner@uchsc.edu    
United States, Michigan
Justus Flechtner, MD, PC Recruiting
Lansing, Michigan, United States, 48910
Contact: Justus Fletchner, MD, PC     517-272-9727     researchinfo21@hotmail.com    
United States, New York
Feinstein Institute for Medical Research NS-LIJ Health System Recruiting
Manhasset, New York, United States, 11030
Contact: Cynthia Aranow, MD     516-562-3837     caranow@nshs.edu    
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: R. John Looney, MD     585-275-5308     John_Looney@urmc.rochester.edu    
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Edna Scarlett     919-684-6150     scarl001@mc.duke.edu    
Carolina Bone and Joint Recruiting
Charlotte, North Carolina, United States, 29425
Contact: Sophia Rosemond     704-541-3055     srosemond@bonesrus.org    
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: Mary Chester Wasko, MD     412-383-8846     waskomc@dom.pitt.edu    
Altoona Center for Clinical Research Recruiting
Duncansville, Pennsylvania, United States, 16635
Contact: Renea Weyandt     814-693-0300     reneaweyandt1125@yahoo.com    
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Amanda Oswald     843-792-2014     Oswalkd@musc.edu    
United States, Utah
University of Utah Not yet recruiting
Salt Lake City, Utah, United States, 84132
Contact: Tracy Frech, MD     801-581-4333     tracy.frech@hsc.utah.edu    
Sponsors and Collaborators
Autoimmunity Centers of Excellence
Investigators
Study Chair: Cynthia Aranow, MD Feinstein Institute for Medical Research NS-LIJ Health System
Study Chair: Betty Diamond, MD Feinstein Institute for Medical Research NS-LIJ Health System
  More Information

Publications:
Responsible Party: DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers: DAIT ARA02
Study First Received: March 13, 2006
Last Updated: May 5, 2009
ClinicalTrials.gov Identifier: NCT00302952     History of Changes
Health Authority: United States: Food and Drug Administration

Study placed in the following topic categories:
Antimetabolites
Autoimmune Diseases
Musculoskeletal Diseases
Antilipemic Agents
Joint Diseases
Arthritis
Connective Tissue Diseases
Arthritis, Rheumatoid
Anticholesteremic Agents
Rheumatic Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lovastatin

Additional relevant MeSH terms:
Antimetabolites
Autoimmune Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Joint Diseases
Antilipemic Agents
Arthritis, Rheumatoid
Enzyme Inhibitors
Rheumatic Diseases
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Musculoskeletal Diseases
Therapeutic Uses
Arthritis
Connective Tissue Diseases
Lovastatin

ClinicalTrials.gov processed this record on May 07, 2009