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Phase 4 N=230 Randomized Single-blind Treatment

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

Atherosclerosis · Hypercholesterolemia

Enrolled (actual)
230
Serious AEs
15.7%
Results posted
Oct 2018
Primary outcome: Primary: Change in Mean of Wall Volume of Internal Carotid Arteries — -3.52; -5.91 Other - mm^3 ( cubic millimeter )

Study Design & Population

Study type
Interventional
Phase
Phase 4
Interventions
Statins, HMG CoA (Drug)
Age
Adult, Older Adult · 50+ yrs
Sex
All
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Primary completion
Nov 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Mean of Wall Volume of Internal Carotid Arteries
-3.52; -5.91

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):

  • Allergy to gadolinium for scans using contrast; will be eligible for non-contrast scans.
  • Acute renal failure, renal transplant, dialysis and renal failure (eGFR
  • 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01212900). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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