protocolSection identificationModule nctId: NCT06319339, orgStudyIdInfo id: 0419-23-FB, briefTitle: Impact of Nrf2 Activation on Macrovascular, Microvascular & Leg Function & Walking Capacity in Peripheral Artery Disease, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-08, primaryCompletionDateStruct date: 2025-08, completionDateStruct date: 2025-08, studyFirstPostDateStruct date: 2024-03-20, lastUpdatePostDateStruct date: 2024-03-20, sponsorCollaboratorsModule leadSponsor name: University of Nebraska, class: OTHER, descriptionModule 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., conditionsModule conditions: Peripheral Artery Disease, conditions: Peripheral Vascular Diseases, conditions: Peripheral Arterial Disease, conditions: Peripheral Arterial Occlusive Disease, designModule studyType: INTERVENTIONAL, phases: EARLY_PHASE1, designInfo 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, maskingInfo masking: DOUBLE, maskingDescription: Double-blinded study, whoMasked: PARTICIPANT, whoMasked: INVESTIGATOR, enrollmentInfo count: 20, type: ESTIMATED, armsInterventionsModule interventions name: Vumerity, interventions name: Placebo, outcomesModule primaryOutcomes measure: Macrovascular Endothelial Function, primaryOutcomes measure: Oxygen Transfer and Utilization, primaryOutcomes measure: Femoral and Popliteal Artery Blood Flow, primaryOutcomes measure: Walking capacity, secondaryOutcomes measure: Autonomic Nervous Activity, secondaryOutcomes measure: Arterial Stiffness, secondaryOutcomes measure: Circulating blood markers of Oxidative Stress and Antioxidants, eligibilityModule sex: ALL, minimumAge: 50 Years, maximumAge: 75 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: University of Nebraska - Omaha, city: Omaha, state: Nebraska, zip: 68182, country: United States, contacts name: Song-Young Park, PhD, role: CONTACT, phone: 402-554-3374, email: song-youngpark@unomaha.edu, geoPoint lat: 41.25626, lon: -95.94043, hasResults: False