Impact of Nrf2 Activation on Macrovascular, Microvascular & Leg Function & Walking Capacity in Peripheral Artery Disease

Recruiting now · Early Phase 1 · Has a placebo group

Conditions studied: Peripheral Artery Disease, Peripheral Vascular Diseases, Peripheral Arterial Disease, Peripheral Arterial Occlusive Disease

In brief

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. 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. There will be a follow-up visit to assess blood work after diroximel fumarate.

Key facts

Study ID: NCT06319339
Run by: University of Nebraska
People needed: 20
Starts: 2024-11-14
Expected to finish: 2026-12-01
Last updated by the study team: 2026-06-24

Who can join

Age: 50 and older, up to 75. Sex: any. Healthy volunteers: accepted.

You may qualify if…

Peripheral artery disease (PAD) participants:
Able to provide written informed consent
50-75 years of age
Diagnosed as Fontaine stage II-III
History of exercise-induced claudication
Females must be postmenopausal (cessation of menses for > 24 months)
Normal renal function (serum creatinine-estimated glomerular filtration rate >= 60 mL/min) or evidence of stable renal function within the last 6 months
Normal hepatic function (alanine transaminase < 87.5 U/L, alkaline phosphatase < 260 U/L, total bilirubin 1.8 mg/dL) or evidence of stable hepatic function within the last 6 months
Complete blood count:
Females: red blood cell 4-5 trillion cells/L, hemoglobin 12-15 g/dL, hematocrit 34-45%, white blood cell count 3-10 billion cells/L, platelet count 160-380 billion/L, and normal lymphocyte count > 700 million lymphocytes/L, or evidence of stable blood counts within the last 6 months
Males: red blood cell 4-6 trillion cells/L, hemoglobin 13-17 g/dL, hematocrit 38-49%, white blood cell count 3-10 billion cells/L, platelet count 135-320 billion/L, and normal lymphocyte count > 700 million lymphocytes/L, or evidence of stable blood counts within the last 6 months
Age-matched control participants:
Able to provide written informed consent
50-75 years of age
No evidence of peripheral occlusive disease (ankle-brachial index > 0.90)
Females must be postmenopausal (cessation of menses for > 24 months)
Normal renal function (serum creatinine-estimated glomerular filtration rate >= 60 mL/min), or evidence of stable renal function within the last 6 months
Normal hepatic function (alanine transaminase < 87.5 U/L, alkaline phosphatase < 260 U/L, total bilirubin 1.8 mg/dL ), or evidence of stable hepatic function within the last 6 months
Complete blood count:
Females: red blood cell 4-5 trillion cells/L, hemoglobin 12-15 g/dL, hematocrit 34-45%, white blood cell count 3-10 billion cells/L, platelet count 160-380 billion/L, and normal lymphocyte count > 700 million lymphocytes/L
Males: red blood cell 4-6 trillion cells/L, hemoglobin 13-17 g/dL, hematocrit 38-49%, white blood cell count 3-10 billion cells/L, platelet count 135-320 billion/L, and normal lymphocyte count > 700 million lymphocytes/L, or evidence of stable blood counts within the last 6 months

You may not qualify if…

Peripheral artery disease (PAD) participants:
• Pain at rest and/or tissue loss due to PAD (Fontaine stage IV PAD)
Acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma
Limited walking capacity from conditions other than PAD
No physical exam to assess exercise limitations in the past year
Currently pregnant or nursing
Blood work and medical history NOT demonstrating:
Normal renal function (serum creatinine-estimated glomerular filtration rate >> 60 mL/min)
Normal hepatic function (alanine transaminase 0-35 IU/L, alkaline phosphatase 30-120 IU/L, total bilirubin 2-17 micromoles/L),
Diagnosis of multiple sclerosis or psoriasis
Diagnosis of gastrointestinal disorders (e.g., moderate IBS, Crohn's disease, etc.
Concomitant use of dimethyl fumarate
Hypersensitivity to diroximel fumarate, dimethyl fumarate, or to any of the excipients of VUMERITY
Ulcers, gangrene, or necrosis of the foot (Fontaine stage IV PAD)
Complete blood count NOT within ranges:
Females: red blood cell 4-5 trillion cells/L, hemoglobin 12-15 g/dL, hematocrit 34-45%, white blood cell count 3-10 billion cells/L, platelet count 160-380 billion/L, and normal lymphocyte count 1-4.8 billion lymphocytes/L
Males: red blood cell 4-6 trillion cells/L, hemoglobin 13-17 g/dL, hematocrit 38-49%, white blood cell count 3-10 billion cells/L, platelet count 135-320 billion/L, and normal lymphocyte count 1-4.8 billion lymphocytes/L
Age-matched control participants:
Positive diagnosis of PAD
No physical exam to assess exercise limitations in the past year
Any exercise limitations as determined at last physical exam
Limited walking capacity from musculoskeletal injury
Currently pregnant or nursing
Renal function not within normal ranges (serum creatinine-estimated glomerular filtration rate >> 60 mL/min)
Hepatic function not within normal ranges (alanine transaminase 0-35 IU/L, alkaline phosphatase 30-120 IU/L, total bilirubin 2-17 micromoles/L)

Where it is running

University of Nebraska - Omaha — Omaha, Nebraska, United States (enrolling)

Full record on ClinicalTrials.gov

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