nctId: NCT06319339 id: 0419-23-FB briefTitle: Impact of Nrf2 Activation on Macrovascular, Microvascular & Leg Function & Walking Capacity in Peripheral Artery Disease overallStatus: NOT_YET_RECRUITING date: 2024-08 date: 2025-08 date: 2025-08 date: 2024-03-20 date: 2024-03-20 name: University of Nebraska class: OTHER briefSummary: Purpose: Peripheral artery disease (PAD) is associated with elevated oxidative stress, and oxidative stress has been implicated as the cause of reduced endothelial reactivity in individuals with PAD. Endothelial function is important because the endothelium contributes to the dilation of arteries during exercise, thereby implicating impaired endothelial function as a mechanism contributing to exacerbated exercise-induced ischemia. Therefore, the purpose of this study is to test the hypothesis that acute exogenous diroximel fumarate (Vumerity) intake will improve antioxidant capacity, thereby reducing oxidative stress and improving vascular function and walking capacity in those with PAD. Eligibility: Individuals with PAD will be deemed eligible for this study if they 1) are 50-75 years old and postmenopausal, 2) have a positive history of exercise-limiting claudication (Fontaine II or III), 3) do not have renal impairments, 4) do not have Fontaine stage IV PAD, and 5) are not currently pregnant or nursing. Age-matched controls will be deemed eligible for this study if they 1) are 50-75 years old and postmenopausal, 2) have an ABI greater than 0.9 (no PAD), 3) do not have exercise-limiting diseases or injuries, 4) do not have renal impairments, and 5) are not currently pregnant or nursing. Intervention and Evaluation: During this study, participants will be administered diroximel fumarate or a placebo, and the acute effects of diroximel fumarate on vascular function and walking capacity will be assessed. Vascular function and walking capacity will be assessed with flow-mediated dilation, arterial stiffness, head-up tilt test, blood biomarkers, near-infrared spectroscopy, and a treadmill test. Follow-up: There will be a follow-up visit to assess blood work after diroximel fumarate. conditions: Peripheral Artery Disease conditions: Peripheral Vascular Diseases conditions: Peripheral Arterial Disease conditions: Peripheral Arterial Occlusive Disease studyType: INTERVENTIONAL phases: EARLY_PHASE1 allocation: RANDOMIZED interventionModel: CROSSOVER interventionModelDescription: There will be a peripheral artery disease (PAD) group and an age-matched healthy control group. Within each of these groups will be a 1:1 randomized, crossover, double-blinded study. primaryPurpose: TREATMENT masking: DOUBLE maskingDescription: Double-blinded study whoMasked: PARTICIPANT whoMasked: INVESTIGATOR count: 20 type: ESTIMATED name: Vumerity name: Placebo measure: Macrovascular Endothelial Function measure: Oxygen Transfer and Utilization measure: Femoral and Popliteal Artery Blood Flow measure: Walking capacity measure: Autonomic Nervous Activity measure: Arterial Stiffness measure: Circulating blood markers of Oxidative Stress and Antioxidants sex: ALL minimumAge: 50 Years maximumAge: 75 Years stdAges: ADULT stdAges: OLDER_ADULT facility: University of Nebraska - Omaha city: Omaha state: Nebraska zip: 68182 country: United States name: Song-Young Park, PhD role: CONTACT phone: 402-554-3374 email: song-youngpark@unomaha.edu lat: 41.25626 lon: -95.94043 hasResults: False