Clinical Utility of Endothelial Dysfunction in PAD
Condition: Peripheral Arterial Disease
MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases
Intervention: atorvastatin; ascorbic acid; Placebo
Intervention description: atorvastatin 40 or 80 mg/day; ascorbic acid 500 mg/day; matching placebo
Intervention MeSH terms: Ascorbic Acid; Atorvastatin
Phase: Phase 1
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 108.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: endothelium; nitric oxide; statins; ascorbic acid

Summary:

      This study will seek to determine whether non-invasive measures of endothelial function have
      utility as surrogate markers of cardiovascular risk in patients with peripheral arterial
      disease undergoing vascular surgery. Measurements of endothelial function will be made before
      and after initiation of atorvastatin, ascorbic acid, or placebo therapy during the
      pre-operative period. We will then examine cardiovascular events following surgery. We
      hypothesize that patients who have no improvement in endothelial function will have increased
      cardiovascular risk compared to patients with improvement in endothelial function.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female subjects age 21-99 years old.

          2. Peripheral Arterial Disease. PAD is defined clinically and by angiography, magnetic
             resonance imaging, vascular ultrasound, or ankle brachial index less than 0.9.

          3. Able to provide informed consent and complete the study procedure.

          4. Patients undergoing non-emergent vascular surgery (peripheral arterial bypass,
             abdominal aortic aneurysm repair, carotid endarterectomy, or limb amputation) or other
             non-cardiac surgery.

        Exclusion Criteria:

          1. Emergent or urgent surgery that must be performed sooner than one week after
             enrollment

          2. Unstable angina, myocardial infarction, stroke, coronary revascularization, or
             decompensated heart failure within 1 month of enrollment. Patients who require cardiac
             catheterization and surgical or percutaneous coronary revascularization prior to
             vascular surgery will be excluded.

          3. Clinically evident major illness of other organ systems, including cancer, end-stage
             renal disease, hepatic failure, or other conditions that make participation
             inappropriate.

          4. Women who are lactating, pregnant, or of childbearing potential and not using a
             reliable contraceptive method. Pregnancy will be excluded by a urine pregnancy test.

          5. Patients with liver function tests or serum creatine kinase >3 times the upper limit
             of normal.

          6. Patients who have received an investigational drug within 30 days of enrollment.

          7. Patients or subjects with a history of a psychological illness or condition such as to
             interfere with the subject's ability to understand the requirements of the study.

          8. Known occlusive atherosclerosis of the subclavian artery or upper extremity, because
             such disease will interfere with induction of reactive hyperemia during the brachial
             artery ultrasound studies.

          9. Patients will be excluded if they are taking vitamin C in a dose greater than 2 times
             the Recommended Daily Allowance (>120 mg/day) within 1 month of enrollment.