Effects of Rosuvastatin on Carotid Artery Plaques in Patients With Inflammatory Joint Disease (RORAAS)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
Diakonhjemmet Hospital
ClinicalTrials.gov Identifier:
NCT01389388
First received: April 16, 2010
Last updated: July 7, 2011
Last verified: September 2010
  Purpose

Patients with rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS) are at greater risk of developing cardiovascular disease. The reason(s) for this have not been well investigated, but there is a general understanding that systemic inflammation plays a part in the increased cardiovascular morbidity and mortality. In spite of the increased risk in these patients, they have not been included as a high risk patient group in cardiovascular prevention guidelines.

The investigators have carried out a cardiovascular study of RA and AS patients, as well as patients with arthritis for the first time. The investigators have demonstrated cholesterol plaques in the carotid artery in some of these patients. Plaques in the carotid artery represent a risk for development of cerebral stroke and are significantly associated with myocardial infarction. These plaques, which are asymptomatic and do not cause haemodynamically significant narrowing, diameter reduction (i.e. operation is not indicated), are vascular atheromatous disease. Therefore, according to prevailing cardiovascular guidelines (SCORE 2007), these patients shall have secondary prevention with a lipid lowering agent with the LDL-cholesterol goal of 1.8 mmol/L and HDL-cholesterol > 1.0 mmol/L for men and > 1.1 mmol/L for women.

Statins are cholesterol-lowering drugs, and have been shown to reduce the risk of cardiovascular disease significantly. In addition, reduction in the size of coronary plaques has been induced by statins, when the LDL has been reduced to 1.6-1.8 mmol/l. Plaques in the carotid or coronary arteries have not previously been treated and characterized in patients with RA, AS and other inflammatory forms of arthritis.

The aim of this study is to treat patients with cholesterol plaques in the carotid artery with cholesterol-lowering medication, in the form of Rosuvastatin for 18 months, and characterize the effects on the plaques in the carotid and coronary arteries. In addition, the investigators want to clarify the connection between plaques in the carotid and coronary arteries in patients with RA, AS and other inflammatory forms of arthritis.


Condition Intervention
Carotid Artery Plaque
Ankylosing Spondylitis
Rheumatoid Arthritis
Drug: Rosuvastatin

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Cholesterol Plaques in Carotid and Coronary Arteries and the Effect of Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases

Resource links provided by NLM:


Further study details as provided by Diakonhjemmet Hospital:

Primary Outcome Measures:
  • Carotid artery cholesterol plaque regression and stabilization [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Reduction of plaque area and change of the plaque morphology to less vulnerable for rupture after 18 months with 40 mg Rosuvastatin daily.


Secondary Outcome Measures:
  • Disease activity and health measures, lipoprotein components and inflammatory biomarkers [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Disease activity and Health status i. Disease activity will be measured by: 28-swollen-joint count, AIMS2, BASDAI ii. Health status will be measured by MHAQ, BASFI, Pain VAS, Fatigue VAS, life quality (HRQoL)

  • Carotid artery cholesterol plaque regression and stabilization [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Lipoprotein components: Lipids, apolipoproteins, magnitude and functional measurements of these, for example of HDL

  • Carotid artery cholesterol plaque regression and stabilization [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Biomarkers/inflammation parameters


Estimated Enrollment: 100
Study Start Date: January 2010
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rosuvastatin intervention
Patients > 70 years will be given Rosuvastatin of 5 mg a day, uptitering the dose until the LDL level of 1.6-1.8 mmol/l has been reached. Patient <70 years, strat on Rosuvastatin 20 mg a day, uptitered to 40 mg a day, with the LDL of 1.6-1.8 mmol/l. -1.8 mmol/l. The objective is that all the participants should have reached a LDL level of 1.6-1.8 mmol/l 3 months after the start of the study. The participants will remain on Rosuvastatin medication for a total of 18 months.
Drug: Rosuvastatin
All the patients who have signed the informed consent will after they have had performed a MCT and possibly SCC with an IVUS, will be give Rosuvastatinuntill their LDL level has reached 1.6-1.8 mmol/l. The objective is that all the participants should have reached 1.6-1.8 mmol/l 3 months after the start of the study. The participants will remain on Rosuvastatin medication for a total of 18 months.
Other Name: Brand name for Rosuvastatin is Crestor

  Eligibility

Ages Eligible for Study:   35 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Women and men with RA, AS and other inflammatory forms of arthritis, aged 35-80 years.
  2. Cholesterol plaques demonstrated in carotid artery by ultrasound.
  3. Informed consent.

Exclusion Criteria:

  1. Concomitant statin treatment
  2. Arterial fibrillation or others with chronic irregular heart rhythm (because of CT).
  3. Contraindication to statin treatment.

    • Hypersensitivity to statins
    • Liver disease with ASAT/ALAT ≥ twice the upper normal limit
    • Previous statin-induced myopathy or severe hypersensitivity reactions to other statins
    • Raised creatinine (because of contrast medium)
    • Pregnancy or breast feeding
    • Fertile women who do not use contraceptives
    • Cyclosporine treatment
    • Treatment with medicinal products that have a known interaction with Rosuvastatin
    • Uncontrolled hypothyroidism defined as TSH > 1.5 times ULN at the first visit (because of the connection between myopathy and hypothyroidism with statin treatment)
    • Creatinine clearance < 30 ml/min and <60 ml/min with a Rosuvastatin dose of 40 mg per day
  4. Secondary hyperlipidemia

    • Primary hyperthyroidism
    • Nephrotic syndrome, creatinine > 2 mg/dl
    • Uncontrolled diabetes mellitus (HbA1C > 10 %)
    • Plasma Triglycerides > 6.8 mmol/l
  5. Other diseases or treatment that reduces the safety, or treatment with Rosuvastatin which would interfere with the end points of the study

    • Heart failure: NYHA class III B/IV
    • Haemodynamically significant valve defects
    • Established statin treatment
    • Gastrointestinal disease/treatment that can give malabsorption of Rosuvastatin
    • Cancer
    • Severe psychiatric disease
    • Life-threatening ventricular arrhythmias
    • Other medication that increases the risk of rhabdomyolysis
    • Known abuse of alcohol
    • Participation in other studies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01389388

Locations
Norway
Anne Grete Semb, Department of Rheumatology, Diakonhjemmet hospital
Oslo, Norway, NO-0319
Sponsors and Collaborators
Diakonhjemmet Hospital
Investigators
Principal Investigator: Anne G Semb, MD, PhD Diakonhjemmet Hospital
  More Information

No publications provided

Responsible Party: Anne Grete Semb, MD, PhD, Diakonhjemmet Hospital
ClinicalTrials.gov Identifier: NCT01389388     History of Changes
Other Study ID Numbers: 2009/2219, 2008-005551-20
Study First Received: April 16, 2010
Last Updated: July 7, 2011
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by Diakonhjemmet Hospital:
Carotid plaques
inflammatory joint disease
statins
inflammation
lipoprotein components

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Carotid Stenosis
Joint Diseases
Spondylitis
Spondylitis, Ankylosing
Ankylosis
Arterial Occlusive Diseases
Autoimmune Diseases
Bone Diseases
Bone Diseases, Infectious
Brain Diseases
Cardiovascular Diseases
Carotid Artery Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Connective Tissue Diseases
Immune System Diseases
Infection
Musculoskeletal Diseases
Nervous System Diseases
Rheumatic Diseases
Spinal Diseases
Spondylarthritis
Spondylarthropathies
Vascular Diseases
Rosuvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 30, 2014