EW-A-401 to Treat Intermittent Claudication

INCLUSION CRITERIA: Adults greater than or equal to 21 years. Limiting lower limb intermittent claudication due to infra-inguinal obstructive atherosclerosis, not optimal for catheter-based treatment. Patient femoral artery inflow by radio contrast or magnetic resonance angiography within the previous 12 months. Stable symptoms for at least 4 months. Peak walking time (PWT) on standardized Gardner Exercise Treadmill Exam between 1 and 12 minutes. Resting ankle-brachial systolic blood pressure index (ABI) less than 0.9 in the more-affected limb. Bilateral PAD for subjects enrolled into Strata C-F with the less-affected limb having any of the following: Resting or post-exercise ABI less than or equal to 0.9. Typical intermittent claudication. Infrainguinal obstructive atherosclerosis in a femoropopliteal and/or tibial artery greater than or equal to 70%. Subjects enrolled into Strata A and B may have both unilateral or bilateral peripheral atherosclerotic disease. EXCLUSION CRITERIA: Any history of malignancy or a known genetic predisposition for developing cancer except for curatively resected basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or resected benign colonic polyps. Non-compressible arteries (resting ankle-brachial systolic blood pressure index (ABI) greater than 1.3 in the more-affected limb). Evidence of malignancy after screening according to modified American Cancer Society Guidelines in the following organ systems (screening procedures in addition to history and physical exam are noted): -Prostate: subjects with the following PSA levels above the recommended age-specific cut-points will be excluded Age 50-59 greater than or equal to 3.7 Age 60-69 greater than or equal to 5.1 Age 70-79 greater than or equal to 7.0 Age 80 plus-greater than or equal to 7.2 Subjects with PSA values above the age-specific cut-points are eligible if a prostate biopsy, within 12 months, shows neither prostate cancer nor high-grade prostatic intraepithelial neoplasia (PIN). Breast: mammogram Cervix: Pap smear Colon: Colonoscopy Skin Lung: contrast chest CT scan Proliferative retinopathy, severe non-proliferative retinopathy, advanced age-related macular degeneration, especially subjects with chorodial neovascularization, diabetic retinopathy, macular edema, or intraocular surgery within 3 months. Limiting symptom on Gardner Exercise Treadmill Examination other than intermittent claudication. Co-morbid conditions that limit exercise capacity: Severe arthritis affecting lower extremities Severe chronic obstructive pulmonary disease Angina pectoris greater than Canadian Angina Class 2 Dyspnea greater than New York Heart Association Class II Cardiovascular surgery or percutaneous revascularization within 4 months. Inclusion is permitted two or more months after successful iliac stenting in the presence of significant infra-inguinal atherosclerotic obstruction. Inclusion is permitted immediately after unsuccessful attempts at percutaneous recanalization of total occlusions of infra-inguinal arteries. Coagulopathy: aPTT greater than 1.4 x mean laboratory normal reference range International Normalized Ration of Prothrombin Time greater than 1.5 Patients on anticoagulation therapy are eligible to participate, with reversal of coagulopathy in accordance with ACC/AHA guidelines, except patients with: Recent arterial (0-1 month) thromboemboism; Recent venous (0-3 months) thromboembolism; Recurrent venous thromboembolism; Non-valvular atrial fibrillation and previous thromboembolism; Mechanical prosthetic valve. Women of childbearing potential. Subjects unwilling to use barrier contraception during the study. Subjects unsuitable for unilateral investigational thigh compression for perfusion measurements due to: Patent femoropopliteal or femorotibial bypass graft or patent femoropopliteal stent on both limbs. Subjects with one of the above features who are amenable to contralateral thigh compression are eligible for enrollment. Immune compromise including chronic HIV, HBV, and HCV infection. Contraindication to Magnetic Resonance Imaging: Allergy to Gadolinium MRI contrast agents. Implanted cardiac pacemaker or defibrillator. Central nervous system aneurysm clips. Implanted neural stimulator. Cochlear implant. Ocular foreign body (e.g. metal shavings). Insulin Pump. Metal shrapnel or bullet. Note: When subjects can provide evidence that their implanted device is labeled compatible with MRI, exceptions to the above exclusions can be made and recorded in the note. Creatinine clearance less than or equal to 20 mL per minute. Creatinine clearance (CLcr) will be estimated using the Cockcroft-Gault formula. Current alcohol, drug abuse, severe medical, psychiatric, behavioral, or emotional disorder of any other condition that may preclude a subject from complying with all requirement of the protocol. Subjects receiving experimental medication or participating in another study receiving an experimental drug or procedure within 30 days prior to enrollment. Unable or unwilling to provide written informed consent.