Randomized Trial of Imaging Versus Risk Factor-Based Therapy for Plaque Regression

This study is currently recruiting participants.
Verified June 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01212900
First received: September 30, 2010
Last updated: March 14, 2014
Last verified: June 2013
  Purpose

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.

Condition Intervention Phase
Atherosclerosis
Hypercholesterolemia
Drug: LDL. Cholesterol (Statin Drugs)
Drug: HMG-CoA Reductase Inhibitors
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Prevention
Official Title: Randomized Trial of Imaging Versus Risk Factor Based Therapy for Plaque Regression

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The primary efficacy endpoint of this study is the wall volume of the internal carotid arteries as measured by magnetic resonance imaging.

Secondary Outcome Measures:
  • A-Arterial stenosis & amp; plaque vol measured by coronary MDCTA, B-Dosage of statin medications required to achieve LDL targets, C-Combined incidence of stroke, nonfatal MI, myocardial revascularization, hospitalization for unstable angina... [ Time Frame: 2 years ]

Estimated Enrollment: 300
Study Start Date: September 2010
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: LDL. Cholesterol (Statin Drugs)
    N/A
    Drug: HMG-CoA Reductase Inhibitors
    N/A
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.

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (section 1.3,above).

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01212900

Contacts
Contact: Marissa B Mallek (301) 496-7700 marissa.mallek@nih.gov
Contact: David A Bluemke, M.D. (301) 402-1854 bluemked@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: David A Bluemke, M.D. National Institutes of Health Clinical Center (CC)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01212900     History of Changes
Other Study ID Numbers: 100214, 10-CC-0214
Study First Received: September 30, 2010
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Atherosclerosis
Cardiovascular Disease
Cardiac MRI
Cardiac CT
Cholesterol

Additional relevant MeSH terms:
Atherosclerosis
Hypercholesterolemia
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 22, 2014