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

NCT00368589 | Completed

• 1 other identifier: TMT106468
• Study Type: observational
• Target: 47
• Locations: 1 country
• Sites: 1

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®.

Conditions

Atherosclerotic Carotid Disease; Atheroma; Atherosclerosis

Keywords

atherosclerotic plaque; USPIO; Atheroma; thrombo-embolic stroke; magnetic resonance imaging; Ultra small Super-Paramagnetic Iron Oxide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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.

Interventions

atorvastatin DRUG

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.)

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 2GG, United Kingdom

Location

Related Publications (2)

• Clezar CN, Flumignan CD, Cassola N, Nakano LC, Trevisani VF, Flumignan RL. Pharmacological interventions for asymptomatic carotid stenosis. Cochrane Database Syst Rev. 2023 Aug 4;8(8):CD013573. doi: 10.1002/14651858.CD013573.pub2.

  PMID: 37565307 DERIVED

• 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. doi: 10.1016/j.jacc.2009.03.018.

  PMID: 19477353 DERIVED

MeSH Terms

Conditions

Carotid Artery Diseases; Plaque, Atherosclerotic; Atherosclerosis

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2006
• First Posted: August 24, 2006
• Study Start: July 1, 2006
• Primary Completion: August 1, 2007
• Study Completion: August 1, 2007
• Last Updated: April 16, 2015

Record last verified: 2015-04

Locations

GB (1)