Improving Exercise Rehabilitation Efficacy Outcomes Veterans Peripheral Artery Disease

Physical activity is the most beneficial and cost-effective treatment for Veterans with PAD, however, issues with oxygen delivery and utilization dramatically impair exercise compliance. The cause of these oxygen delivery and utilization impairments is likely increased oxidative stress and inflammation. The proposed project will comprehensively examine the novel strategy of Nuclear Factor Erythroid-2-like 2 (Nrf2) activation using PB125, aimed at diminishing oxidative stress and inflammation, and thereby lessening the negative impacts of the disease. This therapeutic will be evaluated in isolation and in combination with exercise rehabilitation to determine if there is a complimentary benefit. The ultimate goal is to provide insight into a potential novel therapeutic treatment for this disease, therefore, improving exercise tolerance and quality of life in this growing population.

Inclusion Criteria:Age 40 and older with clinically diagnosed femoropopliteal PAD (ankle-brachial index < 0.9)Must understand the study requirements and be willing and able to sign an informed consent documentPatients with mild cognitive impairment (i.e., montreal cognitive assessment (MOCA) <26) will be included but must have a responsible caregiver or spouse present during the informed consentWomen that are not pregnant, breastfeeding, or likely to become pregnant within the next 6 monthsExclusion Criteria:Patients with a bleeding disorder that would contraindicate the performance of a muscle biopsy, such as a history of clinically significant bleeding diathesis (i.e., Hemophilia A or B, Von Willebrand's Disease, or congenital Factor VII deficiency)Patients with a complex atherosclerotic lesion such that withholding medication creates disproportionate riskWomen currently taking hormone replacement therapyAny other condition or event considered exclusionary by the PI and faculty physician