A 12-week, randomised, double-blind study evaluating the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on macrophage activity and carotid plaque inflammation as determined by ultra small super-paramagnetic iron oxide (USPIO) enhanced carotid magnetic resonance imaging (MRI)

Not Applicable

Completed

• Conditions: Carotid atherosclerosis; Circulatory System

• Registration Number: ISRCTN64894118
• Lead Sponsor: GlaxoSmithKline (UK)

Brief Summary

2009 results in: https://www.ncbi.nlm.nih.gov/pubmed/19477353 (added 10/09/2019) 2011 results in: https://www.ncbi.nlm.nih.gov/pubmed/21483158

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-03-29
• Study Completion: 2009-04-01
• Last Update Posted: 7 October 2019

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

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 screening. 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 will be pre-defined.
4. Must either be statin naive or have been on a stable dose of a statin for =4 weeks prior to screening, with no evidence of statin intolerability

Exclusion Criteria

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
2. History of statin intolerance
3. History of chronic viral hepatitis or other chronic hepatic disorders
4. Renal impairment
5. History of myopathy or inflammatory muscle disease
6. Doppler assessment of less than 40% stenosis during screening assessment
7. Contraindication to MRI scanning
8. Planned carotid surgery or endovascular intervention earlier than 10 weeks within the study period
9. Serum triglycerides >400 mg/dl (4.52 mmol/l) at screening
10. Patients with poorly controlled diabetes mellitus and hypertension
11. History of malignancy
12. Evidence of recent severe infection
13. Current life-threatening condition other than vascular disease
14. Alcohol or drug abuse within the past six months
15. Concomitant use of potent CYP450 3A4 inhibitors
16. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and oral steroids therapy
17. Chronic use of immunosuppressants
18. Use of an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication
19. Any other subject the investigator deems unsuitable for the study (e.g. due to either medical reasons, laboratory abnormalities, expected study medication non-compliance, or subject?s unwillingness to comply with all study-related procedures)
20. Inability to give informed consent

Study & Design

• Study Type: Interventional
• Study Design: Not specified