Clinical trial NCT00302952: Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis
Official title: A Double Blind, Placebo Controlled, Phase II, Randomized Study of Lovastatin Therapy in the Treatment of Mildly Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Arthritis, Rheumatoid
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Autoimmunity Centers of Excellence
First posted: 2006-03-15
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Adjusted Mean Change From Baseline in Log Transformed C - Reactive Protein (CRP) at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscular Hemoglobin Concentration (MCHC) at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Change From Baseline in Potassium, Sodium, Chloride, and Total CO2 at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Change From Baseline in CPK at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Change From Baseline in Hematocrit (Hct) at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Change From Baseline in Red Cell Distribution Width (RDW) at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Change From Baseline in Mean Corpuscular Volume (MCV) at Day 84
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
Secondary outcomes:
measure: Adjusted Mean Change From Baseline in the Disease Activity Score Using C-reactive Protein (DAS28-CRP) on Day 84
timeFrame: Baseline (Day 0) to Day 84 (Wk 12)
measure: Percentage of Participants Meeting ACR20 Response Criteria at Day 84 (ACR: American College of Rheumatology)
timeFrame: Day 84 (Wk 12)
measure: Adjusted Mean Change From Baseline in Serum IgM Rheumatoid Factor by ELISA (ELISA: Enzyme-linked Immunosorbent Assay)
timeFrame: Baseline (Day 0), Day 84 (Wk 12)
measure: Adjusted Mean Change From Baseline in Serum Anti-cyclic Citrullinated Peptide (Anti-CCP) by ELISA (ELISA: Enzyme-linked Immunosorbent Assay)
timeFrame: Baseline ( Day 0), Day 84 (Wk 12)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Lansing
country: United States
facility: Justus J. Fiechtner, MD, PLLC
state: Michigan
city: Manhasset
country: United States
facility: Feinstein Institute for Medical Research NS-LIJ Health System
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Carolina Bone and Joint
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Feinstein Institute for Medical Research NS-LIJ Health System
name: Cynthia Aranow, MD
role: STUDY_CHAIR
affiliation: Feinstein Institute for Medical Research NS-LIJ Health System
name: Betty Diamond, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.