Comprehensive Magnetic Resonance of Peripheral Arterial Disease

The purpose of this study is to develop new ways of imaging fatty blockages in the leg arteries to improve upon techniques used now and to develop new ways of understanding how new treatments may affect the disease.

Study Overview

• Status: Completed
• Conditions: Peripheral Artery Disease
• Intervention / Treatment: Drug: Ezetimibe; Drug: Simvastatin; Drug: Simvastatin/Ezetimibe

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virgina Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients age 30-85 referred to the vascular imaging laboratory with documented evidence of peripheral arterial disease (0.4<ABI<0.9) 96 Normal healthy subjects ages 30-85

Exclusion Criteria:

Age<30, >85

GFR less than 45mL/min based on a serum creatinine drawn within 90 days of the MRI:

Pregnancy Contraindications to a magnetic resonance examination

• Intracranial clips
• Implantable pacemaker and defibrillator
• Cochlear or intraocular implants
• Claustrophobia
• Any metallic implant not listed as magnetic resonance compatible in Shellock F.G ---Pocket Guide to Magnetic Resonance Procedures and Metallic Objects, Update 2000. Lippincott, Williams and Wilkins

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Randomized; Patients are imaged at baseline and randomized to Simvistatin 40 mg each night or Simvistatin 40mg/Zetia 10mg each night for 2 years	Drug: Simvastatin; 40mg each night; Other Names: Zocor; Drug: Simvastatin/Ezetimibe; 40mg/10mg each night; Other Names: Vytorin
Experimental: Ezetemibe; Patients are imaged at baseline and treated with ezetimibe 10mg each night for 2 years.	Drug: Ezetimibe; 10mg daily; Other Names: Zetia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plaque Volume	SFA plaque volume	2 years
Perfusion Index	Perfusion index is a MRI measure of calf muscle perfusion indexed to the arterial input. The value is between 0 and 1 with 0 being worst and 1 being best.	2 years
Phosphocreatine Recovery Time Constant - the Time it Takes for Phosphocreatine Levels to Recover to Plateau.	Phosphocreatine recovery time constant is the time it takes for phosphocreatine levels to recover to plateau after the completion of exercise. This ranges from 20 to 1000 seconds. 20-40 seconds is normal and any value over 40 seconds is abnormal.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low Density Lipoprotein Cholesterol		2 years
Total Cholesterol		2 years
High Density Lipoprotein Cholesterol		2 years
Triglycerides		2 years
Magnetic Resonance Angiographic Index	MRA index is a measure of angiographic severity of disease. 0 = no disease and 4 is severe disease.	2 years
Log Treadmill Exercise Time		2 years
6-minute Walk Distance		2 years
V02 - Maximal Oxygen Consumption		2 years

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Christopher M Kramer, M.D., University of Virginia Health System

Publications and helpful links

General Publications

• Isbell DC, Berr SS, Toledano AY, Epstein FH, Meyer CH, Rogers WJ, Harthun NL, Hagspiel KD, Weltman A, Kramer CM. Delayed calf muscle phosphocreatine recovery after exercise identifies peripheral arterial disease. J Am Coll Cardiol. 2006 Jun 6;47(11):2289-95. doi: 10.1016/j.jacc.2005.12.069. Epub 2006 May 15.
• Isbell DC, Meyer CH, Rogers WJ, Epstein FH, DiMaria JM, Harthun NL, Wang H, Kramer CM. Reproducibility and reliability of atherosclerotic plaque volume measurements in peripheral arterial disease with cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2007;9(1):71-6. doi: 10.1080/10976640600843330. Erratum In: J Cardiovasc Magn Reson. 2007;9(3):629.
• Isbell DC, Epstein FH, Zhong X, DiMaria JM, Berr SS, Meyer CH, Rogers WJ, Harthun NL, Hagspiel KD, Weltman A, Kramer CM. Calf muscle perfusion at peak exercise in peripheral arterial disease: measurement by first-pass contrast-enhanced magnetic resonance imaging. J Magn Reson Imaging. 2007 May;25(5):1013-20. doi: 10.1002/jmri.20899.
• Kramer CM. Peripheral arterial disease assessment: wall, perfusion, and spectroscopy. Top Magn Reson Imaging. 2007 Oct;18(5):357-69. doi: 10.1097/rmr.0b013e31815d064c.
• West AM, Anderson JD, Meyer CH, Epstein FH, Wang H, Hagspiel KD, Berr SS, Harthun NL, DiMaria JM, Hunter JR, Christopher JM, Chew JD, Winberry GB, Kramer CM. The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline. Atherosclerosis. 2011 Sep;218(1):156-62. doi: 10.1016/j.atherosclerosis.2011.04.005. Epub 2011 Apr 16.
• West AM, Anderson JD, Epstein FH, Meyer CH, Wang H, Hagspiel KD, Berr SS, Harthun NL, Weltman AL, Dimaria JM, Hunter JR, Christopher JM, Kramer CM. Low-density lipoprotein lowering does not improve calf muscle perfusion, energetics, or exercise performance in peripheral arterial disease. J Am Coll Cardiol. 2011 Aug 30;58(10):1068-76. doi: 10.1016/j.jacc.2011.04.034.
• Anderson JD, Epstein FH, Meyer CH, Hagspiel KD, Wang H, Berr SS, Harthun NL, Weltman A, Dimaria JM, West AM, Kramer CM. Multifactorial determinants of functional capacity in peripheral arterial disease: uncoupling of calf muscle perfusion and metabolism. J Am Coll Cardiol. 2009 Aug 11;54(7):628-35. doi: 10.1016/j.jacc.2009.01.080.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: December 21, 2007
• First Posted (Estimate): January 7, 2008

Study Record Updates

• Last Update Posted (Actual): August 21, 2017
• Last Update Submitted That Met QC Criteria: July 20, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: PAD
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Ezetimibe
• Other Study ID Numbers: 10387 (Other Identifier: CTEP); R01HL075792 (U.S. NIH Grant/Contract)