Carotid Plaque Regression With Statin Treatment Assessed by High Field Magnetic Resonance Imaging (MRI)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2009 by Medical College of Wisconsin.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT00388843
First received: October 16, 2006
Last updated: January 12, 2009
Last verified: January 2009
  Purpose

The purpose of the study is to determine if short term (6 months) treatment with statins to lower low-density lipoprotein (LDL) in vascular disease patients with carotid plaque will be associated with a measurable reduction in carotid plaque volume using 3 Tesla MRI. The researchers will correlate the change in plaque volume to degree of LDL lowering. The researchers will also study if brief treatment will lead to change in plaque composition. The researchers will compare the change in plaque volume measured by 3T MRI with plaque burden measured by ultrasound.


Condition Phase
Carotid Atherosclerosis
Phase 4

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Short Term Carotid Plaque Regression in Patients With Atherosclerotic Disease Taking Statins Assessed by High Field MRI

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Change in carotid artery plaque volume assessed by carotid MRI at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in carotid intima media thickness on ultrasound at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in plaque composition by carotid MRI at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in inflammatory markers at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in regional wall shear stress in the carotid artery [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 52
Study Start Date: August 2006
Estimated Study Completion Date: February 2009
Estimated Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts
Dose Increased
Patients presenting with symptoms of coronary artery disease or stroke/suspected stroke, with carotid plaque > 1.1 mm, and whose statin dose is increased to moderate to high dose by their clinicians.
Dose Maintained
Patients presenting with symptoms due to coronary artery disease or stroke/suspected stroke, with carotid plaque > 1.1 mm, on no statins or whose statin dose was unchanged by their clinicians.

Detailed Description:

Atherosclerotic vascular disease is the leading cause of death in the United States. Atherosclerosis develops with increasing plaque burden and eccentric arterial wall expansion or remodeling, later leading to luminal obstruction. More than 90% of patients with CAD have carotid plaques. Statins have been shown to cause plaque regression in the carotid and coronary arteries. However, there is ongoing controversy about how low the target LDL should be in atherosclerotic patients. The benefits of aggressive LDL lowering with higher statin doses are counterbalanced by the potential for liver and muscle toxicity. High field (3 Tesla) MRI is a promising new modality for measuring plaque volume with high spatial resolution. It is not clear whether increasing statin dose will lead to plaque volume reduction in the short-term (6 months) that can be measured by this new modality.

The primary aim of the study is to determine if LDL lowering using statins in vascular disease patients with carotid plaque will be associated with measurable reduction in carotid plaque volume in the short term (6 months) using 3T MRI.

The four secondary aims of the study are as follows:

To compare the short term carotid plaque volume change using high field MRI in vascular disease patients whose statin dose was increased (dose increased) versus those whose statin dose was maintained (dose maintained).

To determine if increasing statin dose in patients with carotid plaque will lead to measurable change in carotid plaque composition in the short term (6 months) using 3T MRI.

To compare the carotid plaque volume change using 3T MRI with change in plaque burden score using carotid ultrasound .

To determine the relationship between change in plaque volume with change in lipid levels (total cholesterol, LDL, HDL) and change in inflammatory markers (cytokines, high sensitivity CRP).

The study is significant because it will provide insight into optimal statin treatment for atherosclerotic disease. It will also test a new modality for measurement of plaque burden. A reliable and sensitive test with high spatial resolution that accurately measures change in plaque volume will be helpful in assessing response to treatment and as a tool for future clinical trials in assessing efficacy of new treatment modalities that may reduce the need for expensive, long term studies that rely on clinical events for outcome measurement.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients diagnosed with coronary artery disease or suspected cerebrovascular accident who have carotid plaque (> 1.1 mm) and whose statin dose has been increased to moderate or high dose (increased statin dose) or maintained (maintained statin dose).

Criteria

Inclusion criteria:

  • Adult (> 21 years old) patients.
  • Diagnosed with coronary artery disease or suspected cerebrovascular accident.
  • For dose increased subjects, patients whose statin dose or LDL lowering therapy is doubled or increased from standard dose to high dose (see table).
  • For dose maintained subjects, patients whose statin dose or LDL lowering therapy is maintained at standard dose (see table).
  • Standard Dose (reported LDL↓ < 40% from literature)

    • Drug Daily Dose/s: (md/day)
    • atorvastatin 10
    • simvastatin 5, 10, 20
    • pravastatin 10, 20, 40, 80
    • fluvastatin 20, 40, 80
    • lovastatin 10, 20, 40
  • High Dose (reported LDL↓ > 40% from literature)

    • Drug Daily Dose/s (mg/day)
    • atorvastatin 40, 80
    • simvastatin 40, 80
    • lovastatin 80
    • rosuvastatin 5, 10, 20, 40
    • Addition of non-statin lipid transfer (tx) (e.g., ezetimibe, fibrate, niacin) to standard statin dose

Exclusion criteria:

  • severe claustrophobia causing inability to undergo MRI implanted ferromagnetic materials (pacemakers, defibrillators, TENS units, aneurysm clips, etc.) that are not suitable for MRI in the clinical setting
  • patients anticipated to undergo carotid stenting or surgery in next 6 months
  • patients unable to lie flat for 1 hour
  • patients requiring supplemental oxygen
  • pregnant women
  • patients who could not be followed up for 6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00388843

Contacts
Contact: Raymond Q. Migrino, MD 414-456-6777 rmigrino@mcw.edu

Locations
United States, Wisconsin
Medical College of Wisconsin/Froedtert Memorial and Lutheran Hospital Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Raymond Migrino, MD    414-456-6777    rmigrino@mcw.edu   
Principal Investigator: Raymond Migrino, MD         
Sub-Investigator: Robert Prost, PhD         
Sub-Investigator: Osama Zaidat, MD         
Sub-Investigator: Jason Jurva, MD         
Sub-Investigator: Megan Bright, BS         
Sub-Investigator: Anil Doppalapudi, MD         
Sub-Investigator: Leanne Harmann, RDCS         
Sub-Investigator: Mahazarin Kaikobad, MD         
Sub-Investigator: James Kleczka, MD         
Sub-Investigator: John LaDisa, PhD         
Sub-Investigator: Staci Milosavljevic, MD         
Sub-Investigator: Vinai Roopchansingh, PhD         
Sub-Investigator: Sean Tutton, MD         
Sub-Investigator: Jingli Wang, PhD         
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
Principal Investigator: Raymond Migrino, MD Medical College of Wisconsin
  More Information

Additional Information:
No publications provided

Responsible Party: Raymond Q. Migrino, Department of Medicine, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00388843     History of Changes
Other Study ID Numbers: PRO00002285
Study First Received: October 16, 2006
Last Updated: January 12, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Medical College of Wisconsin:
carotid atherosclerosis
magnetic resonance imaging
atherosclerosis
ultrasound
inflammation
statins
vulnerable plaque
stroke

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Carotid Artery Diseases
Arterial Occlusive Diseases
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Vascular Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014