NCT06319339 · University of Nebraska
Impact of Nrf2 Activation on Macrovascular, Microvascular & Leg Function & Walking Capacity in Peripheral Artery Disease
What this study is about
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.
View original scientific description
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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
Exclusion criteria
- 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)
- 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
Where
- Omaha, Nebraska
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 24, 2026 · Source of record for eligibility and locations