Randomized Trial of Imaging Versus Risk Factor-Based Therapy for Plaque Regression
Condition: Atherosclerosis; Hypercholesterolemia
MeSH terms: Atherosclerosis; Hypercholesterolemia
Intervention: Statins, HMG CoA
Intervention description: Statin therapy
Intervention MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Enrollment: 230.0
Sex: All
Minimum age: 50 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Atherosclerosis; Cardiovascular Disease; Cardiac MRI; Cardiac CT; Cholesterol

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        A. Men and Women greater than or equal to 55 years of age

        B. Candidates for lipid lowering therapy under NCEP ATP III guidelines without
        contraindication to statin therapy

        C. Willing to modify therapy to enroll in the study

        D. Willing to travel to the NIH for follow-up visits.

        E. Able to understand and sign informed consent

        F. Lab Eligibility parameters:

          -  eGFR > 45 mL/min/m2

          -  For age >60 test GFR within 1 week prior to contrast; For age less than or equal to 60
             test within 4 weeks

        INCLUSION CRITERIA FOR THE PET SUBSTUDY:

        Participants who are not participating in the CT Reproducibility study are eligible.

        INCLUSION CRITERIA FOR THE REPRODUCIBILITY SUBSTUDY:

        Patients will be selected who had a one RR interval initial CT scan with less that 10.5 mSv
        estimated radiation dosage and who will not be participating in the PET Substudy.

        EXCLUSION CRITERIA:

        A. Ineligibility for MR imaging due to:

          -  Previous pacemaker implantation

          -  Automatic implantable cardioverter-defibrillator (AICD)

          -  Metal implants or other ferromagnetic devices, or

          -  Foreign material

        B. Claustrophobia

        C. Contra-indication or allergy to statin medications.

        D. Current statin therapy at or above the maximum dosage permitted per study protocol.

        E. Use of fibrates, ezetimibe, niacin, or bile acid binding agents within 6 months of
        screening visit.

        F. Pregnancy and nursing.

        G. Liver failure defined clinically and by laboratory data.

        H. Mental, neurologic or social condition preventing understanding of the rationale,
        procedures, risks and potential benefits associated with the trial.

        I. Any other conditions that precludes safety for MRI and/or CT imaging per the researcher
        s evaluation.

        EXCLUSION FOR PARTICIPATION FOR GADOLINUIM CONTRAST. PARTICIPANTS MAY STILL UNDERGO ALL
        OTHER STUDY EVALUATIONS.

        (Inclusive of the above exclusion criteria):

          1. Allergy to gadolinium for scans using contrast; will be eligible for non-contrast
             scans.

          2. Acute renal failure, renal transplant, dialysis and renal failure (eGFR < 45 mL/min/m2
             and/or clinically diagnosed).

          3. Individuals with a history of liver transplant or severe liver disease.<TAB>

          4. Individuals with hemoglobinopathies or severe asthma.

        EXCLUSION FOR PARTICIPATION FOR IODINATED CONTRAST. PARTICIPANTS MAY STILL UNDERGO ALL
        OTHER SUDY EVALUATIONS.

        Prior hypersensitivity reaction to iodinated contrast injection, renal dysfunction (defined
        as eGFR < 45 mL/min/ m2) or a current clinical diagnosis of renal failure.

        EXCLUSION CRITERIA FOR THE PET SUBSTUDY:

        Patients who are unable or unwilling to comply with the physical activity restrictions or
        fast for 12 hours prior to FDG PET scanning will be excluded. Due to the need for dietary
        manipulation and the maintenance of strict glycemic control we will exclude diabetic
        patients from our initial study sample. Blood glucose measurements before injection must be
        within normal limits, less than 200 mg/dL (11 mmol/L).

        EXCLUSION CRITERIA FOR THE REPRODUCIBILITY

        Patients who did not have a one RR interval initial CT scan. Patients who will participate
        in the PET Substudy.