Effects Of Atorvastatin On Macrophage Activity And Plaque Inflammation Using Magnetic Resonance Imaging - Tabular View

Tracking Information

First Received Date ^ICMJE

August 22, 2006

Last Updated Date

October 9, 2008

Start Date ^ICMJE

July 2006

Current Primary Outcome Measures ^ICMJE

Changes from baseline in USPIO-enhanced MRI signal in carotid plaques at 6 weeks and 12-weeks in low and high dose atorvastatin groups (within groups' comparison).

Original Primary Outcome Measures ^ICMJE

Changes from baseline in USPIO-enhanced MRI signal in carotid plaques at 6 weeks and 12-weeks in low and high dose atorvastatin groups (within groups' comparison).

Change History

Complete list of historical versions of study NCT00368589 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Baseline corrected changes in USPIO-enhanced MRI signal in carotid plaques.Changes from baseline in tensile stress, micro-emboli counts, soluble plasma biomarkers at 12 weeks in low and high dose atorvastatin groups.

Original Secondary Outcome Measures ^ICMJE

Same as current

Descriptive Information

Brief Title ^ICMJE

Effects Of Atorvastatin On Macrophage Activity And Plaque Inflammation Using Magnetic Resonance Imaging

Official Title ^ICMJE

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)

Brief Summary

A new way of scanning narrowing in the arteries (main blood vessels) caused by fatty deposits known as plaques has been developed. Heart attacks and strokes occur when plaques become inflamed, depending on the artery affected. Currently used clinical tests can only tell us how much the vessel is blocked by the plaque and not how inflamed (i.e. dangerous) it is. This new method of scanning using magnetic resonance imaging (MRI) and a special agent called Sinerim can identify inflamed plaques. This study will evaluate patients with plaques in their arteries in their neck at risk of strokes to see whether treatment with a cholesterol-lowering drug called atorvastatin can reduce the amount of inflammation within the artery wall within the first three months of treatment. If this effect can be measured using MRI scanning with the use of Sinerim then the results of this study will provide additional clinical validation of the use of MRI scanning combined with agents such as Sinerem®.

Detailed Description

Study Phase

Phase II

Study Type ^ICMJE

Interventional

Study Design ^ICMJE

Treatment, Randomized, Double-Blind, Parallel Assignment, Efficacy Study

Condition ^ICMJE

Atherosclerotic Carotid Disease
Atheroma

Intervention ^ICMJE

Drug: atorvastatin

Study Arms / Comparison Groups

Publications *

Tang TY, Howarth SP, Miller SR, Graves MJ, Patterson AJ, U-King-Im JM, Li ZY, Walsh SR, Brown AP, Kirkpatrick PJ, Warburton EA, Hayes PD, Varty K, Boyle JR, Gaunt ME, Zalewski A, Gillard JH. The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. J Am Coll Cardiol. 2009 Jun 2;53(22):2039-50.

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

Completion Date

August 2007

Primary Completion Date

August 2007 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion criteria:

Positive Sinerem®-enhanced MRI of carotid plaque confirmed by a consultant neuroradiologist
Must either be statin naive or have been on a stable dose of a statin(Permitted statins and total daily dose are as follows: atorvastatin =10mg, simvastatin =40mg, pravastatin =40mg, fluvastatin =80mg, rosuvastatin =10mg for =4 weeks prior to screening, with no evidence of statin intolerability.)

Exclusion criteria:

Require continued use of non-statin lipid modifying therapies or therapy with any other lipid regulating medications
History of statin intolerance
History of chronic viral hepatitis or other liver dysfunction
Renal impairment with serum creatinine >2.5 mg/dl (>221 mol/L)
History of myopathy or inflammatory muscle disease, or 3 times more than the upper limit of normal levels of total creatinine kinase in serum
Doppler assessment of less than 40% stenosis during screening assessment
Allergy to dextran and iron salts
Contraindication to MRI scanning
Planned carotid surgery or endovascular intervention earlier than 10 weeks within the study period

Gender

Both

Ages

18 Years to 80 Years

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

United Kingdom

Expanded Access Status

Administrative Information

NCT ID ^ICMJE

NCT00368589

Responsible Party

Study Director, GSK

Study ID Numbers ^ICMJE

TMT106468

Study Sponsor ^ICMJE

GlaxoSmithKline

Collaborators ^ICMJE

Investigators ^ICMJE

Study Director:

GSK Clinical Trials, MBBS MRCP

GlaxoSmithKline

Information Provided By

GlaxoSmithKline

Verification Date

October 2008

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP