Randomized Trial of Imaging Versus Risk Factor-Based Therapy for Plaque Regression
Condition: Atherosclerosis; Hypercholesterolemia
MeSH terms: Atherosclerosis; Hypercholesterolemia
Study type: Interventional
Phase: Phase 4

Summary: 
      Background:

      - Atherosclerosis (thickening of the artery walls caused by cholesterol and other deposits)
      commonly occurs in the heart vessels and carotid (neck) arteries of adults. This is often
      present in individuals with high cholesterol levels in their blood. These patients are
      usually treated with cholesterol lowering medication ( statins ) along with modification of
      diet and exercise. Researchers are interested in investigating new approaches including
      magnetic resonance imaging (MRI) and computed tomography (CT) imaging studies to detect blood
      vessel blockages that would not otherwise be detected by cholesterol levels and risk factors
      for heart disease.

      Objectives:

      - To measure atherosclerosis in the heart vessels and carotid arteries using imaging tests
      (computed tomography (CT) and magnetic resonance imaging (MRI)) before and after standard
      treatment with cholesterol lowering medication ( statins )

      Eligibility:

      - Healthy individuals at least 55 years of age who are candidates for therapy to lower their
      blood cholesterol levels.

      Design:

        -  This study will involve one screening visit and seven study visits over a period of 2
           years.

        -  Participants will be screened with a physical examination and medical history, as well
           as blood samples and tests to ensure that it is safe for them to have CT and MRI scans.
           Participants will provide information on current medications, dietary habits, smoking
           status, alcohol and caffeine intake, and their level of physical activity.

        -  Participants will be divided into two groups. One group will receive standard doses of
           medication to lower cholesterol according to current treatment guidelines, while the
           other group will have MRI scans of the carotid arteries and a CT scan of the heart to
           determine the best medication dose levels.

        -  Visits 3 to 5 will be scheduled 3, 6, and 9 months after visit 2. During these visits,
           researchers will monitor for possible side effects and may change or adjust medications
           and doses.

        -  At visit 6, participants will have an MRI scan of the carotid arteries, a physical
           examination, and blood tests. Medications may be changed or adjusted.

        -  At visit 7, participants will have blood tests, and medications may be changed or
           adjusted.

        -  At the final visit, participants will have MRI and CT scans of the carotid arteries and
           heart, respectively, as well as a final physical examination and blood tests.
    

Detailed description: 
      The overall aim of this proposal is to compare the effectiveness of an image guided approach
      to lipid lowering to standard therapy guided by clinical risk factors and blood lipid levels.
      Men and women over age 55 who are candidates for statin therapy will be randomized to usual
      cholesterol lowering care, or to care guided by MRI images of the carotid arteries.
      Participants randomized to the second, imaging guided, group will be assigned to LDL
      cholesterol targets according to the degree of atherosclerosis seen by MRI. The study
      endpoints will be the total degree of plaque regression seen, the dosage of statin drugs
      required to achieve that reduction, and the rate of cardiovascular events.

      FDG-PET is hypothesized to enable visualization of anti-inflammatory effects of statins that
      most likely occur before anatomic regression of the plaques can be demonstrated on MRI. A
      pilot substudy is to be conducted to explore this relationship. A subgroup of patients
      participating in the main study will be asked to participate in FDG PET imaging. The purpose
      of this pilot study is to determine if FDG avid lesions undergo a greater degree of
      morphologic regression with therapy controlling for the reduction in LDL cholesterol and the
      dosage of statins required to achieve that target.

      Although contrast-enhanced coronary CT angiography (CTA) with multidetector computed
      tomography (MDCT) has been used extensively to characterize coronary artery plaque
      composition, there is little data regarding its reproducibility. A recent study demonstrated
      excellent reproducibility for this technique but this study was performed using the older 64
      detector row CT scanners2. A pilot substudy will be conducted to study the reproducibility of
      coronary CT angiography using the newer generation of 320 detector row CT scanners.
    

Intervention name(s): Statins, HMG CoA
Intervention type(s): Drug
Intervention description(s): Statin therapy
Intervention MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Atherosclerosis; Cardiovascular Disease; Cardiac MRI; Cardiac CT; Cholesterol