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

NCT01212900 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 10021410-H-0214
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Atherosclerosis; Hypercholesterolemia

Keywords

Atherosclerosis; Cardiovascular Disease; Cardiac MRI; Cardiac CT; Cholesterol

Outcome Measures

Primary Outcomes (1)

• Change in Mean of Wall Volume of Internal Carotid Arteries

  Wall volume of internal carotid arteries was measured using magnetic resonance imaging. Participants will undergo 2D and 3D carotid MRI using a 3 Tesla scanner and surface carotid coils. Participants with mild or no atherosclerosis, defined as the lowest tertile of wall volume, will have statin therapy adjusted to a target range of 100-130 mg/dL. Participants in the middle tertile will receive statin therapy adjusted to achieve a target LDL 70-100 mg/dL. Participants with the most severe atherosclerosis will receive statin therapy to an LDL target between 40 and 70 mg/dL. Participants in the Standard arm will have lipid sub-fraction targets determined according to estimated 10 year cardiovascular risk, as per standard NCEP guidelines.

  24 months

Study Arms (2)

Imaging

EXPERIMENTAL

Lipid targets assigned according to the severity of atherosclerotic plaque measured as wall volume in the common and internal carotid arteries by MRI

Drug: Statins, HMG CoA

Standard

ACTIVE COMPARATOR

Standardized statin therapy based on NCEP ATP IIIR guidelines, including clinical risk factors and blood lipid levels.

Drug: Statins, HMG CoA

Interventions

Statins, HMG CoA DRUG

Statin therapy

Imaging; Standard

Eligibility Criteria

• Age: 50 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Participants who are not participating in the CT Reproducibility study are eligible.
• 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.

You may not qualify if:

• 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.
• Allergy to gadolinium for scans using contrast; will be eligible for non-contrast scans.
• Acute renal failure, renal transplant, dialysis and renal failure (eGFR \< 45 mL/min/m2 and/or clinically diagnosed).

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Zavodni AE, Wasserman BA, McClelland RL, Gomes AS, Folsom AR, Polak JF, Lima JA, Bluemke DA. Carotid artery plaque morphology and composition in relation to incident cardiovascular events: the Multi-Ethnic Study of Atherosclerosis (MESA). Radiology. 2014 May;271(2):381-9. doi: 10.1148/radiol.14131020. Epub 2014 Mar 4.

  PMID: 24592924 BACKGROUND

• Polak JF, Szklo M, Kronmal RA, Burke GL, Shea S, Zavodni AE, O'Leary DH. The value of carotid artery plaque and intima-media thickness for incident cardiovascular disease: the multi-ethnic study of atherosclerosis. J Am Heart Assoc. 2013 Apr 8;2(2):e000087. doi: 10.1161/JAHA.113.000087.

  PMID: 23568342 BACKGROUND

• Sibley CT, Vavere AL, Gottlieb I, Cox C, Matheson M, Spooner A, Godoy G, Fernandes V, Wasserman BA, Bluemke DA, Lima JA. MRI-measured regression of carotid atherosclerosis induced by statins with and without niacin in a randomised controlled trial: the NIA plaque study. Heart. 2013 Nov;99(22):1675-80. doi: 10.1136/heartjnl-2013-303926. Epub 2013 Jul 19.

  PMID: 23872591 BACKGROUND

• Sandfort V, Lai S, Ahlman MA, Mallek M, Liu S, Sibley CT, Turkbey EB, Lima JA, Bluemke DA. Obesity Is Associated With Progression of Atherosclerosis During Statin Treatment. J Am Heart Assoc. 2016 Jul 13;5(7):e003621. doi: 10.1161/JAHA.116.003621.

  PMID: 27413040 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Atherosclerosis; Hypercholesterolemia; Cardiovascular Diseases

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Results Point of Contact

• Title: Mehta, Nehal
• Organization: National Heart Lung and Blood Institute

mehtann@mail.nih.gov

+1 301 827 0483

Study Officials

• Nehal N Mehta, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2010
• First Posted: October 1, 2010
• Study Start: September 30, 2010
• Primary Completion: November 30, 2016
• Study Completion: February 22, 2017
• Last Updated: November 30, 2018
• Results First Posted: October 31, 2018

Record last verified: 2018-02-12

Locations

US (1)