Effects of HMG-coA Reductase Inhibitor on Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT00555230
• Recruitment Status: Completed
• First Posted: November 8, 2007
• Last Update Posted: January 27, 2011
• Sponsor: Chinese University of Hong Kong
• Information provided by: Chinese University of Hong Kong

Study Description

Brief Summary:

The purpose of this study is:

1. To evaluate the prevalence of preclinical atherosclerosis in Chinese patients with RA compared to healthy controls.
2. To determine those clinical and biological measures that best predict the presence of plaque and increased arterial stiffness.
3. To ascertain the efficacy and safety of rosuvastatin in the prevention of atherosclerosis in patients with RA measured by carotid intima-media thickness (IMT) and pulse wave velocity (PWV).

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: Rosuvastatin; Drug: Placebo	Phase 2

Detailed Description:

150 consecutive RA patients followed at the Rheumatology clinic of the Prince of Wales Hospital will be recruited for this double-blind, randomized, placebo-control trial. Patients were matched to 150 controls on the basis of age (within 5 years), sex, body mass index (+/-5Kg) and ethnicity for the cross sectional study on the prevalence of subclinical atherosclerosis. Controls were healthy individuals recruited from the same community who underwent similar imaging protocols of the IMT and PWV assessments.

Primary outcome is the improvement of atherosclerosis by Rosuvastatin therapy, evaluated by IMT and PWV.

Secondary outcomes:

• Prevalence of premature atherosclerosis in RA patients compared to healthy controls in terms of the presence of plague and PWV.
• Correlation between clinical parameters, inflammatory markers (CRP/hsCRP, TNF-alpha and IL-6) and atherosclerosis (evaluated by IMT, the presence of plaque and PWV).
• Relation among PWV, ABI and AI in RA patients, and clinical significance of their combination.
• Determine which segment's PWV has a better relation with RA disease activity.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of HMG-coA Reductase Inhibitor on Progression of Carotid Intima-Media Thickness and Arterial Stiffness in Rheumatoid Arthritis
• Study Start Date: July 2007
• Actual Primary Completion Date: December 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Rosuvastatin	Drug: Rosuvastatin; 5mg daily for 4 weeks then step up to 10mg or matching placebo for 52 weeks; Other Name: crestor
Placebo Comparator: 2; Placebo	Drug: Placebo; 5mg daily for 4 weeks then step up to 10mg or matching placebo for 52 weeks; Other Name: crestor

Outcome Measures

Primary Outcome Measures :

1. Improvement of atherosclerosis by Rosuvastatin therapy, evaluated by IMT and PWV. [ Time Frame: baseline,week24,week52 ]

Secondary Outcome Measures :

1. physical examination,blood pressure,pulse rate,and body weight measurements at each visit.Liver function and CK are performed at baseline,week 12,24 and 52.Correlation between clinical parameters,inflammatory markers and atherosclerosis. [ Time Frame: baseline,week0,week3,week8,week12,week24,week36,week52 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men or women, 18 years of age or older
• Clinical diagnosis of RA with a duration of at least 6 month
• Prednisolone < =10 mg/day
• NSAID or DMARD
• Informed consent

Exclusion Criteria:

• Little or no ability for self-care
• Type 1 diabetes mellitus
• Uncontrolled hypertension(> 160/95 mmHg)
• Total cholesterol > 240 mg/dl, current or recent (within the past 3 months)
• History of coronary bypass grafting, myocardial infraction within 28days, left ventricular dysfunction (ejection fraction < 40%), significant valvular heart disease
• Current treatment with ACE inhibitor, angiotensin II receptor blockers or beta-blockers, lipid lowering drug, or contra-indication to statins
• Current treatment of oral contraceptives, estrogen and progestin was allowed but patient not willing to stop during study
• Current treatment with antioxidant therapy (Vitamin C or multivitamin)
• Received intra-articular, intramuscular, or intravenous corticosteroids in the past 4 weeks before screening
• Clinically significant renal disease(serum creatinine level ≥ 270 µmol/L) or aspartate aminotransferase(AST), alanine aminotransferase ALT), or creatine kinase (CK)≥ 2 X ULN
• Female of childbearing potential, unwilling to use adequate contraception during the study
• Current or recent (within the past 3 months) pregnancy and cancer

Contacts and Locations

Locations

China

School of Pharmacy CUHK

Hong Kong, China

Sponsors and Collaborators

Chinese University of Hong Kong

Investigators

• Principal Investigator: Edmund Kwok Ming Li, MD; Chinese University of Hong Kong

More Information

• Responsible Party: Edumun K Li,MD, the Chinese University of Hong Kong
• ClinicalTrials.gov Identifier: NCT00555230
• Other Study ID Numbers: RA-2007-004
• First Posted: November 8, 2007
• Last Update Posted: January 27, 2011
• Last Verified: December 2008

Keywords provided by Chinese University of Hong Kong:

HMG-CoA reductase inhibitors; Crestor; Rosuvastatin

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Rosuvastatin Calcium; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors