A Double Blind, Placebo Controlled, Phase II, Randomized Study of Lovastatin Therapy in the Treatment of Mildly Active Rheumatoid Arthritis
Overview
- Phase
- Phase 2
- Intervention
- Lovastatin
- Conditions
- Rheumatoid Arthritis
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 64
- Locations
- 15
- Primary Endpoint
- Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
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.
Investigators
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
Arms & Interventions
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.
Intervention: Lovastatin
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal_laboratory_values/blood_tests_normal_values.html
Change From Baseline in CPK at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal_laboratory_values/blood_tests_normal_values.html
Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscular Hemoglobin Concentration (MCHC) at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal_laboratory_values/blood_tests_normal_values.html
Change From Baseline in Potassium, Sodium, Chloride, and Total CO2 at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal_laboratory_values/blood_tests_normal_values.html
Change From Baseline in Mean Corpuscular Volume (MCV) at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal_laboratory_values/blood_tests_normal_values.html
Adjusted Mean Change From Baseline in Log Transformed C - Reactive Protein (CRP) at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood draw for CRP, an acute phase reactant used to identify the presence of nonspecific inflammation. Change=Day 84 value minus Baseline value. Normal serum CRP reference range in this study is 0-4 mg/L (log transformed: -4.2 to 1.4). Participants with measurements for designated time points were included in analysis. An increased CRP level indicates the presence of inflammation. Reduced CRP levels could mean a decrease in inflammation.
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal_laboratory_values/blood_tests_normal_values.html
Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal_laboratory_values/blood_tests_normal_values.html
Change From Baseline in Red Cell Distribution Width (RDW) at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal_laboratory_values/blood_tests_normal_values.html
Change From Baseline in Hematocrit (Hct) at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal_laboratory_values/blood_tests_normal_values.html
Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Day 84
Time Frame: Baseline (Day 0), Day 84 (Wk 12)
Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal_laboratory_values/blood_tests_normal_values.html
Secondary Outcomes
- Adjusted Mean Change From Baseline in the Disease Activity Score Using C-reactive Protein (DAS28-CRP) on Day 84(Baseline (Day 0) to Day 84 (Wk 12))
- Percentage of Participants Meeting ACR20 Response Criteria at Day 84 (ACR: American College of Rheumatology)(Day 84 (Wk 12))
- Adjusted Mean Change From Baseline in Serum IgM Rheumatoid Factor by ELISA (ELISA: Enzyme-linked Immunosorbent Assay)(Baseline (Day 0), Day 84 (Wk 12))
- Adjusted Mean Change From Baseline in Serum Anti-cyclic Citrullinated Peptide (Anti-CCP) by ELISA (ELISA: Enzyme-linked Immunosorbent Assay)(Baseline ( Day 0), Day 84 (Wk 12))