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Rheumatoid ArthritisPhase 2NCT00302952

Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis

A Phase 2 study testing Lovastatin in people with Rheumatoid Arthritis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Lovastatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
64 participants
Where
15 sitesUnited States
Study dates
6 Nov 2007to 30 Apr 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • University of Colorado

    Aurora, Colorado, 80095

  • University of Alabama

    Birmingham, Alabama, 35294

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolina Bone and Joint

    Charlotte, North Carolina, 29425

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Baylor Research Institute

    Dallas, Texas, 75231

  • Altoona Center for Clinical Research

    Duncansville, Pennsylvania, 16635

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Justus J. Fiechtner, MD, PLLC

    Lansing, Michigan, 48910

  • Feinstein Institute for Medical Research NS-LIJ Health System

    Manhasset, New York, 11030

  • Oklahoma Medical Research Foundation

    Oklahoma City, Oklahoma, 73104

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15261

  • University of Rochester

    Rochester, New York, 14642

  • University of Utah

    Salt Lake City, Utah, 84132

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Lovastatin, Placebo
Keywords
Arthritis, Rheumatoid
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LovastatinDrug

    Also called Altoprev, Mevacor, Mevinolin

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

  • PlaceboDrug

    Also called Inactive drug (pharmacologically)

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

Study groups in NCT00302952
Study groupRoleWhat they receive
LovastatinExperimentalParticipants 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.
Receives: Drug: Lovastatin
PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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

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

  3. 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

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

  4. 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

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

  5. 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

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

  6. 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

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

  7. 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

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

  8. 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

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

  9. 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

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

  10. 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

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

  11. 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

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

Secondary outcomes (4)

  1. Adjusted Mean Change From Baseline in the Disease Activity Score Using C-reactive Protein (DAS28-CRP) on Day 84

    The DAS28-CRP score is on a scale of 0 to 10 and indicates current activity of rheumatoid arthritis (>5.1=high disease activity; 3.2-<=5.1=moderate disease activity; <=3.2=low disease activity; <2.6=remission). The score uses a combination of four variables: 1) the number of tender joints (of the 28 that are measured); 2) the number of swollen joints (of the 28 that are measured); 3) serum C-reactive protein (CRP) lab value in mg/L , and 4) Patient Global Assessment of Disease Activity. Using a formula, the physician determines the score. Participants with measurements for designated time points included in analysis.

    Measured: Baseline (Day 0) to Day 84 (Wk 12)

  2. Percentage of Participants Meeting ACR20 Response Criteria at Day 84 (ACR: American College of Rheumatology)

    Patients were ACR20 Responders if they had: at least 20% improvement in both tender joint count (28 examined) and swollen joint count (28 examined), and 20% improvement in at least three of the following 5 remaining ACR core measures: • Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) • Patient's global assessment of disease activity (VAS 100 mm) • Physician's global assessment of disease activity (VAS 100 mm) • Patient self-assessed disability (Health Assessment Questionnaire (HAQ)) score • Acute phase reactant C-reactive protein. Participants with measurements for designated time points were included in analysis.

    Measured: Day 84 (Wk 12)

  3. Adjusted Mean Change From Baseline in Serum IgM Rheumatoid Factor by ELISA (ELISA: Enzyme-linked Immunosorbent Assay)

    Rheumatoid factor (RF) is an antibody often present in the blood of a person with rheumatoid arthritis. In this study, a positive value for RF was 0.5 IU/mL or greater; a negative value for RF was <0.5 IU/mL. Change= Day 84 value minus Baseline value. In general, presence of the antibody indicates aggressive rheumatoid arthritis and higher risk of joint damage. Participants with measurements for designated time points included in analysis.

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

  4. Adjusted Mean Change From Baseline in Serum Anti-cyclic Citrullinated Peptide (Anti-CCP) by ELISA (ELISA: Enzyme-linked Immunosorbent Assay)

    Anti-CCP antibodies are autoantibodies frequently detected in the serum of individuals with rheumatoid arthritis. In this study, a positive value for anti-CCP was 8 IU/mL or greater; a negative value for anti-CCP was <8 IU/mL. Change= subtraction of Day 0 from Day 84 anti-CCP value. In general, high levels of the antibody indicate an aggressive rheumatoid arthritis and a higher risk of joint damage. Participants with measurements for designated time points included in analysis.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2006 (estimated)
  2. Study start6 Nov 2007
  3. Primary completion30 Apr 2012
  4. Study completion30 Apr 2012

Why it stopped: Slow enrollment \&Study Drug Expiration (Target: 40 randomized participants /arm)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00302952
Sponsor's protocol ID
DAIT ARA02
Status last verified
Aug 2022
First submitted
13 Mar 2006
Last updated
7 Sep 2022
Data monitoring committee
Yes
Individual data sharing
Yes: Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

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. doi: 10.1191/0961203303lu429oa.

    PubMed 12945719

  • 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.

    PubMed 15207950

  • 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.

    PubMed 31628482

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lovastatin in people with Rheumatoid Arthritis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adjusted Mean Change From Baseline in Log Transformed C - Reactive Protein (CRP) at Day 84 (time frame: Baseline (Day 0), Day 84 (Wk 12)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00302952, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2022.

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