A Trial of Rosuvastatin in Systemic Lupus Erythematosus

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01170585
First received: July 26, 2010
Last updated: January 18, 2013
Last verified: January 2013
  Purpose

Systemic Lupus Erythematosus (SLE) is a condition that affects the whole body. It can cause inflammation of the blood vessels resulting in an earlier thickening and hardening of the arteries resulting in strokes. It has been reported that SLE can worsen the function resulting in heart failure.

The aim of the study is to examine what effects Rosuvastatin, a cholesterol lowering drug, given to patients has on the degree of thickening of the arteries over the course of two years. We also want to see how it affects the function of the blood vessels and also of the heart.

Individuals who agree to participate will be randomly assigned into two groups. One group will be given the active drug whereas the other will have a placebo. Subjects in the study will all have a cardiac magnetic resonance (CMR) scan before treatment, at 1 year and then 2 years at the end of the treatment. Each scan will involve imaging the carotid arteries in the neck, the arteries in the arm and also the heart. Individuals will continue to have regular out-patient reviews by their own team of doctors, regular blood tests will be taken to monitor the disease and also to ensure the safety and well being of the individual.

At the end of the 2 year study we hope that we will be able to slow down the rate of arterial thickening and retard any plaque build up in the arteries. We also want to see what effect rosuvastatin has on heart function. Ultimately, we hope to prove that people with SLE should be treated with a cholesterol lowering drug as part of their routine treatment.


Condition Intervention Phase
Atherosclerosis
Systemic Lupus Erythematosus
Drug: Rosuvastatin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised Placebo Controlled Trial of Rosuvastatin in Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Change from baseline in bilateral carotid artery wall volume and distensibility [ Time Frame: 3 CMR of 24 months (baseline; 12 and 24 mnths) ] [ Designated as safety issue: No ]

    A series of 20 contiguous 2 dimensional images, centred about the carotid bifurcation will be obtained. These images are then used to calculate the vessel area, but because they are contiguous a three dimensional structure can be formed and the vessel volume can be calculated. These values can be plotted against age and sex-matched graphs of normal ranges.

    The carotid artery distensibility will be calculated by obtaining a short cine film of the carotid artery as it pulsates. This can be contoured in the diastolic and systolic phases of the cardiac cycle.



Secondary Outcome Measures:
  • Endothelial function assessed by brachial artery reactivity. [ Time Frame: 3 CMR, baseline; 12 and 24 mnths. ] [ Designated as safety issue: No ]
    Endothelial function is assessed by imaging the area of the brachial artery at baseline & post intervention.Endothelial dependent function will be assessed by inflating a blood pressure cuff around the forearm for 5 minutes to occlude arterial blood flow and create hyperaemia on release which induces brachial artery dilation by shear effects on endothelium.Glyceryl trinitrate spray will be given to the patient, and further images will be obtained.Both sets of images will be compared to the baseline and the percentage change in vessel size calculated providing a measure of endothelial function.

  • Correlation of vascular findings to ventricular volumes and function [ Time Frame: baseline; 12 and 24 months ] [ Designated as safety issue: No ]
    The correlation of ventricular indices in SLE patients is determined through assessment of cardiac function. Patients will have left and right ventricular volumes measured, allowing calculation of the ejection fraction. These will be compared with age and sex matched normal subjects


Estimated Enrollment: 60
Study Start Date: July 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
randomised to placebo.
Drug: Placebo
Placebo
Active Comparator: Active
randomised to rosuvastatin.
Drug: Rosuvastatin
All patients will be uptitrated from an initial start dose of 5mg to 20mg rosuvastatin. This will be given once a day for 2 years.
Other Name: Crestor

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with SLE-as diagnosed by ACR criteria
  • Male or females who are 18-80years of age, inclusive at screening
  • Female subjects who are post menopausal (i.e >6mnths without menstrual period), surgically sterile, or using effective contraceptive measures at visit 0 and the same contraception throughout the study and for 30days after discontinuing treatment
  • No current or previous statin therapy
  • No current indication for statin therapy (Coronary artery disease; hypercholesterolemia, renal dysfunction)
  • Subjects who have given their signed consent to participate in the study

Exclusion Criteria:

  • Patient < 18 or > 80 years
  • Contraindications for MRI - patients with pacemakers' defibrillators or pacing wires in the heart, or other metal implants such as metal in the eye, brain or spine. Other metallic devices or implants will have to be declared by the participant and assessed to be safe prior to having an MRI current or previous statin
  • Known atherosclerotic valvular disease
  • Renal dysfunction
  • Hyperlipidemia
  • Active myositis
  • All forms of liver disease
  • Pregnancy
  • Breastfeeding
  • Patients being treated with Cyclosporin A
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01170585

Locations
United Kingdom
Imperial College NHS Trust
London, United Kingdom
North West London Hospitals NHS Trust
London, United Kingdom
Sponsors and Collaborators
Imperial College London
Investigators
Principal Investigator: Dudley J Pennell, MD CMR Unit, Royal Brompton Hospital, London
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01170585     History of Changes
Other Study ID Numbers: 2006-006214-16
Study First Received: July 26, 2010
Last Updated: January 18, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Atherosclerosis
Lupus Erythematosus, Systemic
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rosuvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014