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CompletedNCT00587678Updated Aug 21, 2017Results posted

Comprehensive Magnetic Resonance of Peripheral Arterial Disease

An interventional study of Simvastatin and Ezetimibe in Peripheral Artery Disease, sponsored by University of Virginia. Completed at 1 site in United States. Open to participants aged 30 Years to 85 Years. Per ClinicalTrials.gov, last updated 2017-08-21.

Sponsored by University of Virginia · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
85
Allocation
Randomized
Ages
30 Years to 85 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Peripheral Artery Disease

Keywords

  • PAD
03

In context

Peripheral Arterial Disease

1,542 studies on the registry are indexed under Peripheral Arterial Disease; 282 are open to participants now.

This study's enrollment of 85 is above the median of 74 across 1,066 interventional studies indexed under Peripheral Arterial Disease.

Browse Peripheral Arterial Disease studies →

Lead sponsor

University of Virginia is the lead sponsor of 653 studies on the registry; 134 are open to participants now.

Of its 60 completed or terminated interventional studies of FDA-regulated products, 41 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
85 participants (actual)

Study arms

  • 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 · Drug: Simvastatin/Ezetimibe

  • Experimental
    Ezetemibe

    Patients are imaged at baseline and treated with ezetimibe 10mg each night for 2 years.

    Drug: Ezetimibe

Interventions

  • DrugSimvastatin

    40mg each night

    Also known as: Zocor

  • DrugEzetimibe

    10mg daily

    Also known as: Zetia

  • DrugSimvastatin/Ezetimibe

    40mg/10mg each night

    Also known as: Vytorin

06

What researchers measure

Primary outcomes

  1. Plaque Volume

    SFA plaque volume

    Time frame: 2 years

  2. 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.

    Time frame: 2 years

  3. 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.

    Time frame: 2 years

Secondary outcomes

  1. Low Density Lipoprotein Cholesterol

    Time frame: 2 years

  2. Total Cholesterol

    Time frame: 2 years

  3. High Density Lipoprotein Cholesterol

    Time frame: 2 years

  4. Triglycerides

    Time frame: 2 years

  5. Magnetic Resonance Angiographic Index

    MRA index is a measure of angiographic severity of disease. 0 = no disease and 4 is severe disease.

    Time frame: 2 years

  6. Log Treadmill Exercise Time

    Time frame: 2 years

  7. 6-minute Walk Distance

    Time frame: 2 years

  8. V02 - Maximal Oxygen Consumption

    Time frame: 2 years

07

Results

Posted Feb 3, 2012

Participant flow

Participant flow — Overall Study
MilestoneSimvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
Started222241
Completed161833
Not completed648

Outcome measures

PrimaryPlaque Volume

SFA plaque volume

Time frame:
2 years
Reported as:
Mean · cm^3
Plaque Volume
cm^3Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
Plaque Volume10.5 ± 1.410.5 ± 1.310.8 ± 0.9
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg · Linear repeated measures model · p = 0.32
  • Ezetimibe 10mg · Linear repeated measures model · p = <0.01 (vs. baseline)
SecondaryLow Density Lipoprotein Cholesterol
Time frame:
2 years
Reported as:
Mean · mg/dl
Low Density Lipoprotein Cholesterol
mg/dlSimvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
Low Density Lipoprotein Cholesterol83 ± 1168 ± 1077 ± 5
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg · Linear repeated measures model · p = 0.31
  • Ezetimibe 10mg · Linear repeated measures model · p = <0.05 (vs. baseline)
PrimaryPerfusion 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.

Time frame:
2 years
Reported as:
Mean · Units on a scale (0 = worst, 1 = best)
Perfusion Index
Units on a scale (0 = worst, 1 = best)Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
Perfusion Index0.34 ± 0.190.37 ± 0.130.54 ± 0.20
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg vs Ezetimibe 10mg · Linear repeated measures model · p = 0.71
PrimaryPhosphocreatine 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.

Time frame:
2 years
Reported as:
Mean · seconds
Phosphocreatine Recovery Time Constant - the Time it Takes for Phosphocreatine Levels to Recover to Plateau.
secondsSimvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
Phosphocreatine Recovery Time Constant - the Time it Takes for Phosphocreatine Levels to Recover to Plateau.84 ± 6873 ± 3574 ± 58
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg vs Ezetimibe 10mg · Linear repeated measures model · p = 0.67
SecondaryTotal Cholesterol
Time frame:
2 years
Reported as:
Mean · mg/dl
Total Cholesterol
mg/dlSimvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
Total Cholesterol152 ± 12136 ± 12144 ± 6
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg · Linear repeated measures model · p = 0.37
  • Ezetimibe 10mg · Linear repeated measures model · p = <0.05 (vs. baseline)
SecondaryHigh Density Lipoprotein Cholesterol
Time frame:
2 years
Reported as:
Mean · mg/dl
High Density Lipoprotein Cholesterol
mg/dlSimvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
High Density Lipoprotein Cholesterol44 ± 446 ± 343 ± 3
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg vs Ezetimibe 10mg · Linear repeated measures model · p = 0.78
SecondaryTriglycerides
Time frame:
2 years
Reported as:
Mean · mg/dl
Triglycerides
mg/dlSimvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
Triglycerides171 ± 30119 ± 20152 ± 15
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg vs Ezetimibe 10mg · Linear repeated measures model · p = 0.68
SecondaryMagnetic Resonance Angiographic Index

MRA index is a measure of angiographic severity of disease. 0 = no disease and 4 is severe disease.

Time frame:
2 years
Reported as:
Mean · units on scale (0 = normal, 4 = worst)
Magnetic Resonance Angiographic Index
units on scale (0 = normal, 4 = worst)Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
Magnetic Resonance Angiographic Index0.71 ± 0.461.32 ± 0.860.63 ± 0.64
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg · Linear repeated measures model · p = <0.05
SecondaryLog Treadmill Exercise Time
Time frame:
2 years
Reported as:
Mean · log time in seconds
Log Treadmill Exercise Time
log time in secondsSimvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
Log Treadmill Exercise Time5.92 ± 1.085.79 ± 0.675.78 ± 0.63
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg vs Ezetimibe 10mg · linear repeated measures model · p = =0.67
Secondary6-minute Walk Distance
Time frame:
2 years
Reported as:
Mean · ft.
6-minute Walk Distance
ft.Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
6-minute Walk Distance1078 ± 4851038 ± 2481099 ± 394
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg vs Ezetimibe 10mg · Linear repeated measures model · p = 0.77
SecondaryV02 - Maximal Oxygen Consumption
Time frame:
2 years
Reported as:
Mean · ml/min/kg
V02 - Maximal Oxygen Consumption
ml/min/kgSimvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mg
V02 - Maximal Oxygen Consumption14.8 ± 4.612.1 ± 2.912.3 ± 4.6
Statistical analysis
  • Simvastatin 40mg vs Simvastatin 40mg/Ezetimibe 10 mg vs Ezetimibe 10mg · Linear repeated measures model · p = 0.85

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Simvastatin 40mg—0/24 (0%)0/22 (0%)
Simvastatin 40mg/Ezetimibe 10 mg—0/22 (0%)0/22 (0%)
Ezetimibe 10mg—0/41 (0%)0/41 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mgTotal
<=18 years0000
Between 18 and 65 years16112047
>=65 years6112138
Age, Continuous
Age, Continuous(years)Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mgTotal
Mean59 ± 1264 ± 966 ± 1163 ± 11
Sex: Female, Male
Sex: Female, Male(Participants)Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mgTotal
Female6102137
Male16122048
Region of Enrollment
Region of Enrollment(participants)Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mgTotal
United States22224185
Total cholesterol
Total cholesterol(mg/dl)Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mgTotal
Mean194 ± 11189 ± 10170 ± 6182 ± 45
Low density lipoprotein cholesterol
Low density lipoprotein cholesterol(mg/dl)Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mgTotal
Mean118 ± 10118 ± 9100 ± 4111 ± 35
High density lipoprotein cholesterol
High density lipoprotein cholesterol(mg/dl)Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mgTotal
Mean45 ± 448 ± 442 ± 243 ± 13
Triglycerides
Triglycerides(mg/dl)Simvastatin 40mgSimvastatin 40mg/Ezetimibe 10 mgEzetimibe 10mgTotal
Mean227 ± 47130 ± 21157 ± 20159 ± 104

9 further baseline measures are reported on the registry.

08

Study locations

1 site
  • University of Virgina Health System
    Charlottesville, Virginia 22908, United States
09

References and documents

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. PubMed 16750698 ↗
  • 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. PubMed 17178683 ↗
  • 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. PubMed 17410566 ↗
  • 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. PubMed 18025990 ↗
  • 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. PubMed 21570685 ↗
  • 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. PubMed 21867844 ↗
  • 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. PubMed 19660694 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 21, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00587678
Lead sponsor
University of Virginia
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
Responsible party
Christopher M. Kramer MD (Professor of Radiology and Medicine, University of Virginia) — Principal investigator
First posted
Jan 7, 2008
Start date
Jan 2006
Primary completion
Oct 2009
Completion
Oct 2009
Results posted
Feb 3, 2012
Last update
Aug 21, 2017

Study contacts

Christopher M Kramer, M.D.
principal investigator · University of Virginia Health System

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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