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

Sponsored by:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00368589

Purpose

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®.

Condition	Intervention	Phase
Atherosclerotic Carotid Disease Atheroma	Drug: atorvastatin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Parallel Assignment, Efficacy Study
Official Title:	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)

Resource links provided by NLM:

MedlinePlus related topics: MRI Scans Nuclear Scans

Drug Information available for: Atorvastatin Atorvastatin calcium

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

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).

Secondary Outcome Measures:

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.

Enrollment:	47
Study Start Date:	July 2006
Study Completion Date:	August 2007
Primary Completion Date:	August 2007 (Final data collection date for primary outcome measure)

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00368589

Locations

United Kingdom, Cambridgeshire
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 2GG

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials, MBBS MRCP

GlaxoSmithKline

More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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.

Responsible Party:	GSK ( Study Director )
Study ID Numbers:	TMT106468
Study First Received:	August 22, 2006
Last Updated:	October 9, 2008
ClinicalTrials.gov Identifier:	NCT00368589 History of Changes
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:

thrombo-embolic stroke
atherosclerotic plaque
magnetic resonance imaging

Ultra small Super-Paramagnetic Iron Oxide
USPIO
Atheroma

Study placed in the following topic categories:

Atherosclerosis
Arterial Occlusive Diseases
Antimetabolites
Cerebral Infarction
Antilipemic Agents
Stroke
Vascular Diseases

Arteriosclerosis
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Inflammation
Embolism
Iron
Atorvastatin

Additional relevant MeSH terms:

Atherosclerosis
Arterial Occlusive Diseases
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Vascular Diseases
Enzyme Inhibitors
Arteriosclerosis

Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Inflammation
Pathologic Processes
Therapeutic Uses
Cardiovascular Diseases
Atorvastatin

ClinicalTrials.gov processed this record on August 12, 2009