A 12 week, randomised, double blind study evaluating the effects of low dose (10mg) and high dose (80mg) atorvastatin on macrophage activity and carotid plaque inflammation as determined by Ultra small Super-Paramagnetic Iron Oxide (USPIO) enhanced carotid Magnetic Resonance Imaging (MRI)
- Conditions
- Atherosclerotic Carotid Disease
- Registration Number
- EUCTR2005-005703-42-GB
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
A subject will be eligible for inclusion in this study only if all of the following criteria are met:
1. Signed written informed consent prior to beginning study-related procedures (subject must understand the aims, investigational procedures and possible consequences of the study).
2. Male or female aged 18 to 80 years of age at Screen. Female subjects must be of non-childbearing potential (post-menopausal females who have been amenorrheic >1 year, or pre-menopausal females with a documented hysterectomy or bilateral oophorectomy).
3. Positive USPIO-enhanced MRI of carotid plaque confirmed by a consultant neuroradiologist. This is defined as a signal decrease of =10% in 2 or more quadrants between pre-Sinerem and post-Sinerem MRI scans.
4. Must either be statin naïve or have been on a stable dose of a statin1 for =4 weeks prior to screening, with no evidence of statin intolerability.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Required continued use of non-statin lipid modifying therapies (e.g. fibric acid derivatives, niacin, resins, ezetimibe, fish oil supplements, etc.) or therapy with any other lipid regulating medications not specified as study treatment in the protocol.2
2. History of statin intolerance.
3. History of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody), or other chronic hepatic disorders; or ALT or AST >1.5 x ULN, or alkaline phosphatase or total bilirubin >1.5 x ULN of laboratory reference range at screening.
4. Renal impairment with creatinine clearance <50 ml/min (defined by Cockcroft-Gault
formula).
5. History of myocardial infarction or cerebrovascular accident within the past 2 weeks.
6.History of myopathy or inflammatory muscle disease, or elevated total serum CK (3 x ULN) at screening visit.
7. Doppler assessment of less than 40% stenosis during screening assessment.
8. History of clinically significant atopy (e.g. anaphylaxis, skin rash to medication or
topical therapies, hypersensitivity to iodinated contrasts, allergies to food (e.g.
shellfish), bronchial asthma, etc.) or allergy to dextran and iron salts.
9. Contraindication to MRI scanning including but not limited to:
• Intracranial aneurysm clips (except Sugita) with an appropriate operative conformation,
• History of intra- orbital metal fragments that have not been removed by an MD,
• Pacemakers and non-MR compatible heart valves,
• Inner ear implants,
• History of claustrophobia in MR.
10. Planned carotid surgery or endovascular intervention earlier than 10 weeks within the study period.
11. Serum triglycerides >400 mg/dl (4.52 mmol/L) at screening.
12. Untreated or uncontrolled hypothyroidism or thyrotoxicosis.
13. Patients with poorly controlled diabetes mellitus with HbA1c =8.5%.
14. Patients with poorly controlled hypertension (SBP=160 mmHg and/or DBP=100 mmHg).
15. History of malignancy within the past 2 years, other than non-melanoma skin cancer.
16. Evidence of recent (<4 weeks) severe infection (e.g. pneumonia, cellulites, etc.).
17. Current life-threatening condition other than vascular disease (e.g., severe chronic airways disease, HIV positive, life-threatening arrhythmias) that may prevent a subject from completing the study.
18. Alcohol or drug abuse within the past 6 months.
19. Concomitant use of potent CYP450 3A4 inhibitors (e.g. clarithromycin, grapefruit juice [> 8 oz (240 ml) daily], itraconazole, ketoconazole, etc.).
20. Chronic use of NSAIDS and oral steroids therapy.3
21. Chronic use of immunosuppressants (cyclosporine, methotrexate, etc.).
22. Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication.
23. Any other subject the investigator and GSK medical monitor deems unsuitable for the study (e.g., due to either medical
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method