Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis

NCT00302952 | Terminated Phase 2 Results DMC

• 1 other identifier: DAIT ARA02
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 15

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.

Conditions

Rheumatoid Arthritis

Keywords

Arthritis, Rheumatoid

Outcome Measures

Primary Outcomes (11)

• Adjusted Mean Change From Baseline in Log Transformed C - Reactive Protein (CRP) at Day 84

  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.

  Baseline (Day 0), Day 84 (Wk 12)

• Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at Day 84

  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

  Baseline (Day 0), Day 84 (Wk 12)

• Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84

  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

  Baseline (Day 0), Day 84 (Wk 12)

• Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscular Hemoglobin Concentration (MCHC) at Day 84

  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

  Baseline (Day 0), Day 84 (Wk 12)

• Change From Baseline in Potassium, Sodium, Chloride, and Total CO2 at Day 84

  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

  Baseline (Day 0), Day 84 (Wk 12)

• Change From Baseline in CPK at Day 84

  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

  Baseline (Day 0), Day 84 (Wk 12)

• Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84

  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

  Baseline (Day 0), Day 84 (Wk 12)

• Change From Baseline in Hematocrit (Hct) at Day 84

  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

  Baseline (Day 0), Day 84 (Wk 12)

• Change From Baseline in Red Cell Distribution Width (RDW) at Day 84

  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

  Baseline (Day 0), Day 84 (Wk 12)

• Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Day 84

  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

  Baseline (Day 0), Day 84 (Wk 12)

• Change From Baseline in Mean Corpuscular Volume (MCV) at Day 84

  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

  Baseline (Day 0), Day 84 (Wk 12)

Secondary Outcomes (4)

• 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)

Study Arms (2)

Lovastatin

EXPERIMENTAL

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.

Drug: Lovastatin

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Lovastatin DRUG

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

Also known as: Altoprev, Mevacor, Mevinolin

Lovastatin

Placebo DRUG

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

Also known as: Inactive drug (pharmacologically)

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence: collaborator

Study Sites (15)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado

Aurora, Colorado, 80095, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Justus J. Fiechtner, MD, PLLC

Lansing, Michigan, 48910, United States

Location

Feinstein Institute for Medical Research NS-LIJ Health System

Manhasset, New York, 11030, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Carolina Bone and Joint

Charlotte, North Carolina, 29425, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor Research Institute

Dallas, Texas, 75231, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (3)

• 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.

  PMID: 12945719 BACKGROUND

• 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.

  PMID: 15207950 BACKGROUND

• 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.

  PMID: 31628482 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Lovastatin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Enrollment was slow and the full sample size was not obtained.

Results Point of Contact

• Title: Associate Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2006
• First Posted: March 15, 2006
• Study Start: November 6, 2007
• Primary Completion: April 30, 2012
• Study Completion: April 30, 2012
• Last Updated: September 7, 2022
• Results First Posted: February 12, 2014

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share

Locations

US (15)