Evaluate Carotid Artery Plaque Composition by Magnetic Resonance Imaging in People Receiving Cholesterol Medication (CPC)

May 16, 2022 updated by: Xue-Qiao Zhao, University of Washington

Carotid Plaque Composition by Magnetic Resonance Imaging During Lipid Lowering Therapy

Atherosclerosis is a condition that occurs when fatty deposits build up along the inner walls of arteries. This study will examine the effectiveness of a combination of cholesterol-lowering medications at decreasing the fat content of atherosclerotic deposits in people who have coronary artery disease or carotid artery disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Atherosclerosis is a condition in which deposits of fat, cholesterol, and other substances build up along the inner walls of arteries; these deposits are known as plaque. People with atherosclerosis are at risk of developing coronary artery disease, in which plaque build-up occurs in the arteries that supply blood to the heart, and carotid artery disease, in which plaque build-up occurs in the arteries that deliver blood through the neck to the brain. These conditions can lead to blood clots, heart attack, and stroke. Research has shown that people who have more fat content in atherosclerotic plaque may have a higher risk of experiencing a heart attack or stroke. Treatments for atherosclerosis include lifestyle changes, medicines, and medical procedures or surgery. There are several medications that can aid people in controlling their cholesterol levels, including atorvastatin, a medication that inhibits the production of cholesterol; niacin, a B-complex vitamin that can reduce cholesterol levels in combination with dietary changes; and colesevelam, a medication that inhibits fat absorption. Using magnetic resonance imaging (MRI), this study will evaluate whether these medications, alone or in combination, can decrease the fat content of atherosclerotic plaques within the carotid arteries of people with coronary artery disease and carotid artery disease.

This study will enroll people with coronary artery disease or carotid artery disease. Participants will be randomly assigned to one of the following 40-month treatment groups:

  • Group 1 participants will receive atorvastatin, placebo niacin, and placebo colesevelam each day.
  • Group 2 participants will receive atorvastatin, niacin, and placebo colesevelam each day.
  • Group 3 participants will receive atorvastatin, niacin, and colesevelam each day.

At a baseline study visit, participants will undergo a blood collection and will receive dietary counseling that will focus on lowering cholesterol levels. They will also undergo an MRI scan of their carotid arteries. For the next 4 months, participants will attend monthly study visits for repeat blood collection and dietary counseling; for the subsequent 36 months, participants will attend study visits every other month. Repeat carotid artery MRI scans will occur at Months 12, 24, and 36. At three different times during the study, researchers will ask participants to record their food consumption for 3 consecutive days.

Study Type

Interventional

Enrollment (Actual)

217

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90089
        • University of Southern California
    • Idaho
      • Boise, Idaho, United States, 83712
        • St. Luke's Idaho Cardiology
    • Washington
      • Seattle, Washington, United States, 98104
        • University of Washington Coronary Atherosclerosis Research Lab
      • Yakima, Washington, United States, 98902
        • Yakima Heart Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Clinically established coronary artery disease or carotid artery disease with greater than 15% stenosis by ultrasound
  • Family history of cardiovascular disease
  • Apolipoprotein B level greater than or equal to 120 mg/dL (LDL level should be between 100 and 190 mg/dL without medication)
  • Has been undergoing lipid therapy for no more than 12 months before study entry
  • Medically stable
  • Medically able to undergo MRI procedure

Exclusion Criteria:

  • Uses pacemaker or has metallic implants
  • Has immediate plans for carotid endarterectomy
  • History of alcohol or drug abuse
  • Active liver disease or liver dysfunction, defined by elevations in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels greater than 1.5 times the upper limit of normal
  • Serum creatine kinase (CK) level greater than 3 times the upper limit of normal before study entry
  • Serum creatinine level greater than 2.5 times the upper limit of normal
  • Diabetes, with a fasting glucose level greater than 150 mg/dL or hemoglobin A1c (HbA1c) level greater than 8% before study entry
  • Uncontrolled high blood pressure, defined as average resting systolic blood pressure greater than 200 mm Hg or average resting diastolic blood pressure greater than 95 mm Hg

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: 1 - single therapy group
Participants will receive atorvastatin, placebo niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the single therapy group.
Drug: Atorvastatin
10 to 80 mg of atorvastatin each day
Other Names:
  • Lipitor
Drug: Placebo Niacin
Placebo niacin each day
Drug: Placebo Colesevelam
Placebo colesevelam each day
EXPERIMENTAL: 2 - double therapy group
Participants will receive atorvastatin, niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the double therapy group.
Drug: Atorvastatin
10 to 80 mg of atorvastatin each day
Other Names:
  • Lipitor
Drug: Placebo Colesevelam
Placebo colesevelam each day
Drug: Niacin
2000 mg of niacin each day
Other Names:
  • Niaspan
  • Slo-niacin
EXPERIMENTAL: 3 - triple therapy group
Participants will receive atorvastatin, niacin, and colesevelam. The treatment target for LDL-C will be ≤60 mg/dl for the triple therapy group
Drug: Atorvastatin
10 to 80 mg of atorvastatin each day
Other Names:
  • Lipitor
Drug: Niacin
2000 mg of niacin each day
Other Names:
  • Niaspan
  • Slo-niacin
Drug: Colesevelam
3.8 g of colesevelam each day
Other Names:
  • WelChol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized LRNC Volume Change in Carotid Plaque Composition, as Assessed by MRI
Time Frame: Measured at Years 1, 2, and 3

The primary endpoint of this study is carotid plaque lipid composition identified by MRI. The determination of plaque lipid content for each carotid artery will be performed using the automated interactive system. These measurements will be performed from the MRI scans at four time points blinded to time sequence of MRI examinations, patient treatment, lipid levels and clinical course.

Volume Measurements: Contours were placed around the lumen, outer-wall boundaries, and plaque features of carotid artery. (Arterial wall area) = (outer-wall area) - (lumen area). Volume calculated as: area x 2 mm (slice thickness). Tissue volume/wall volume x (100%) is presented as percentage. Annualized change presented mm^3/year (for volume) and as percentage change/year.
Measured at Years 1, 2, and 3
Annualized LRNC and Wall Volume Changes in Carotid Plaque Composition, as Assessed by MRI
Time Frame: Measured at Years 1, 2, and 3

The primary endpoint of this study is carotid plaque lipid composition identified by MRI. The determination of plaque lipid content for each carotid artery will be performed using the automated interactive system. These measurements will be performed from the MRI scans at four time points blinded to time sequence of MRI examinations, patient treatment, lipid levels and clinical course.

Volume Measurements: Contours were placed around the lumen, outer-wall boundaries, and plaque features of carotid artery. (Arterial wall area) = (outer-wall area) - (lumen area). Volume calculated as: area x 2 mm (slice thickness). Tissue volume/wall volume x (100%) is presented as percentage. Annualized change presented mm^3/year (for volume) and as percentage change/year.
Measured at Years 1, 2, and 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of Cardiovascular Endpoints: Number of Participants With Cardiovascular Disease Death, Non-fatal Heart Attack, Stroke, and Worsening Ischemia Requiring Medical Interventions
Time Frame: Measured at Years 3, 4, and 5
Any cardiovascular events such as death from any cause, nonfatal myocardial infarction, stroke, and revascularization procedures (PCI or CABG) due to unstable ischemia will be recorded and verified.
Measured at Years 3, 4, and 5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Pfizer
Daiichi Sankyo, Inc.
Abbott
Upsher-Smith Laboratories

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 1, 2001

Primary Completion (ACTUAL)

December 12, 2018

Study Completion (ACTUAL)

March 1, 2019

Study Registration Dates

First Submitted

July 11, 2008

First Submitted That Met QC Criteria

July 11, 2008

First Posted (ESTIMATE)

July 15, 2008

Study Record Updates

Last Update Posted (ACTUAL)

June 7, 2022

Last Update Submitted That Met QC Criteria

May 16, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00001165
  • R01HL063895-05A1 (NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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