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

NCT00715273 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: STUDY00001165R01HL063895-05A1
• Study Type: interventional
• Target: 217
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Coronary Artery Disease; Carotid Artery Diseases; Atherosclerosis

Keywords

Magnetic Resonance Imaging; Atherosclerotic Plaque; Lipid Lowering Therapy

Outcome Measures

Primary Outcomes (2)

• Annualized LRNC Volume Change in Carotid Plaque Composition, as Assessed by MRI

  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

  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 Outcomes (1)

• Composite of Cardiovascular Endpoints: Number of Participants With Cardiovascular Disease Death, Non-fatal Heart Attack, Stroke, and Worsening Ischemia Requiring Medical Interventions

  Measured at Years 3, 4, and 5

Study Arms (3)

1 - single therapy group

ACTIVE COMPARATOR

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; Drug: Placebo Niacin; Drug: Placebo Colesevelam

2 - double therapy group

EXPERIMENTAL

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; Drug: Niacin; Drug: Placebo Colesevelam

3 - triple therapy group

EXPERIMENTAL

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; Drug: Niacin; Drug: Colesevelam

Interventions

Atorvastatin DRUG

10 to 80 mg of atorvastatin each day

Also known as: Lipitor

1 - single therapy group; 2 - double therapy group; 3 - triple therapy group

Niacin DRUG

2000 mg of niacin each day

Also known as: Niaspan, Slo-niacin

2 - double therapy group; 3 - triple therapy group

Colesevelam DRUG

3.8 g of colesevelam each day

Also known as: WelChol

3 - triple therapy group

Placebo Niacin DRUG

Placebo niacin each day

1 - single therapy group

Placebo Colesevelam DRUG

Placebo colesevelam each day

1 - single therapy group; 2 - double therapy group

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Pfizer: collaborator
• Abbott: collaborator
• Daiichi Sankyo: collaborator
• Upsher-Smith Laboratories: collaborator

Study Sites (4)

University of Southern California

Los Angeles, California, 90089, United States

Location

St. Luke's Idaho Cardiology

Boise, Idaho, 83712, United States

Location

University of Washington Coronary Atherosclerosis Research Lab

Seattle, Washington, 98104, United States

Location

Yakima Heart Center

Yakima, Washington, 98902, United States

Location

Related Publications (12)

• Zhao XQ, Phan BA, Chu B, Bray F, Moore AB, Polissar NL, Dodge JT Jr, Lee CD, Hatsukami TS, Yuan C. Testing the hypothesis of atherosclerotic plaque lipid depletion during lipid therapy by magnetic resonance imaging: study design of Carotid Plaque Composition Study. Am Heart J. 2007 Aug;154(2):239-46. doi: 10.1016/j.ahj.2007.04.035.

  PMID: 17643572 RESULT

• Moore A, Phan BA, Challender C, Williamson J, Marcovina S, Zhao XQ. Effects of adding extended-release niacin and colesevelam to statin therapy on lipid levels in subjects with atherosclerotic disease. J Clin Lipidol. 2007 Dec;1(6):620-5. doi: 10.1016/j.jacl.2007.09.001. Epub 2007 Sep 15.

  PMID: 21291704 RESULT

• Green PS, Vaisar T, Pennathur S, Kulstad JJ, Moore AB, Marcovina S, Brunzell J, Knopp RH, Zhao XQ, Heinecke JW. Combined statin and niacin therapy remodels the high-density lipoprotein proteome. Circulation. 2008 Sep 16;118(12):1259-67. doi: 10.1161/CIRCULATIONAHA.108.770669. Epub 2008 Sep 2.

  PMID: 18765395 RESULT

• Phan BA, Munoz L, Shadzi P, Isquith D, Triller M, Brown BG, Zhao XQ. Effects of niacin on glucose levels, coronary stenosis progression, and clinical events in subjects with normal baseline glucose levels (<100 mg/dl): a combined analysis of the Familial Atherosclerosis Treatment Study (FATS), HDL-Atherosclerosis Treatment Study (HATS), Armed Forces Regression Study (AFREGS), and Carotid Plaque Composition by MRI during lipid-lowering (CPC) study. Am J Cardiol. 2013 Feb 1;111(3):352-5. doi: 10.1016/j.amjcard.2012.09.034. Epub 2012 Nov 17.

  PMID: 23168285 RESULT

• Ronsein GE, Hutchins PM, Isquith D, Vaisar T, Zhao XQ, Heinecke JW. Niacin Therapy Increases High-Density Lipoprotein Particles and Total Cholesterol Efflux Capacity But Not ABCA1-Specific Cholesterol Efflux in Statin-Treated Subjects. Arterioscler Thromb Vasc Biol. 2016 Feb;36(2):404-11. doi: 10.1161/ATVBAHA.115.306268. Epub 2015 Dec 17.

  PMID: 26681752 RESULT

• Zhao XQ, Yuan C, Shah PK. Imaging to Assess the Effect of Anti-Inflammatory Therapy in Aortic and Carotid Atherosclerosis. J Am Coll Cardiol. 2016 Oct 18;68(16):1781-1784. doi: 10.1016/j.jacc.2016.08.011. No abstract available.

  PMID: 27737745 RESULT

• Chu MP, Many G, Isquith DA, McKeeth S, Williamson J, Neradilek MB, Colletti P, Zhao XQ. Metabolic and inflammatory risk reduction in response to lipid-lowering and lifestyle modification in the medically underserved individuals. Am J Prev Cardiol. 2021 Jul 31;7:100227. doi: 10.1016/j.ajpc.2021.100227. eCollection 2021 Sep.

  PMID: 34401861 RESULT

• Han T, Paramsothy P, Hong J, Isquith D, Xu D, Bai H, Neradilek M, Gill E, Zhao XQ. High-resolution MRI assessed carotid atherosclerotic plaque characteristics comparing men and women with elevated ApoB levels. Int J Cardiovasc Imaging. 2020 Mar;36(3):481-489. doi: 10.1007/s10554-019-01600-1. Epub 2020 Feb 4.

  PMID: 32020410 RESULT

• Zhao XQ, Dong L, Hatsukami T, Phan BA, Chu B, Moore A, Lane T, Neradilek MB, Polissar N, Monick D, Lee C, Underhill H, Yuan C. MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course. JACC Cardiovasc Imaging. 2011 Sep;4(9):977-86. doi: 10.1016/j.jcmg.2011.06.013.

  PMID: 21920335 RESULT

• Dong L, Kerwin WS, Chen H, Chu B, Underhill HR, Neradilek MB, Hatsukami TS, Yuan C, Zhao XQ. Carotid artery atherosclerosis: effect of intensive lipid therapy on the vasa vasorum--evaluation by using dynamic contrast-enhanced MR imaging. Radiology. 2011 Jul;260(1):224-31. doi: 10.1148/radiol.11101264. Epub 2011 Apr 14.

  PMID: 21493792 RESULT

• Kerwin WS, Zhao X, Yuan C, Hatsukami TS, Maravilla KR, Underhill HR, Zhao X. Contrast-enhanced MRI of carotid atherosclerosis: dependence on contrast agent. J Magn Reson Imaging. 2009 Jul;30(1):35-40. doi: 10.1002/jmri.21826.

  PMID: 19557844 RESULT

• Ronsein GE, Vaisar T, Davidson WS, Bornfeldt KE, Probstfield JL, O'Brien KD, Zhao XQ, Heinecke JW. Niacin Increases Atherogenic Proteins in High-Density Lipoprotein of Statin-Treated Subjects. Arterioscler Thromb Vasc Biol. 2021 Aug;41(8):2330-2341. doi: 10.1161/ATVBAHA.121.316278. Epub 2021 Jun 17.

  PMID: 34134520 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Carotid Artery Diseases; Atherosclerosis; Plaque, Atherosclerotic

Interventions

Atorvastatin; Niacin; Colesevelam Hydrochloride

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Allylamine; Amines; Organic Chemicals; Allyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons

Results Point of Contact

• Title: Xue-Qiao Zhao
• Organization: University of Washington

xueqiao@uw.edu

206-744-8305

Study Officials

• Xue-Qiao Zhao, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 11, 2008
• First Posted: July 15, 2008
• Study Start: May 1, 2001
• Primary Completion: December 12, 2018
• Study Completion: March 1, 2019
• Last Updated: June 7, 2022
• Results First Posted: June 7, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)