An Early Phase 1 interventional study of Vumerity and Placebo in Peripheral Artery Disease, Peripheral Vascular Diseases and Peripheral Arterial Disease, sponsored by University of Nebraska. Recruiting at 1 site in United States. Open to participants aged 50 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-24.
Sponsored by University of Nebraska · Early Phase 1, Interventional, and Treatment
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.
Peripheral artery disease (PAD), which affects an estimated 200 million individuals worldwide, is characterized by the development of atherosclerotic plaques in the conduit arteries of the back and legs, and leads to exercise-limiting ischemic muscle pain, soft tissue ulcers, gangrene, and ultimately amputation. The pathophysiology of PAD is multifaceted and includes macro-vascular dysfunction, micro-vascular dysfunction, and muscle myopathy. A popular hypothesis for the tissue damage that occurs after conduit artery stenosis is the ischemia-reperfusion hypothesis. Under this hypothesis, intermittent periods of ischemia and hypoxia, followed by rapid oxygen reperfusion, ultimately leads to the production of excessive reactive oxygen species (ROS) in the ischemic tissues, and the intermittent elevations in ROS may exacerbate the degradation of mitochondrial function. Damage to mitochondria may then lead to greater ROS production, thereby creating a vicious cycle of oxidative stress damage and subsequent damage to muscles and blood vessels distal to a stenosis. In alignment with this hypothesis, it has been demonstrated that those with PAD have impaired blood vessel function, demonstrated by low endothelial reactivity. Furthermore, it seems that the reduced vascular reactivity in those with PAD may be partially caused by elevated ROS production, since the introduction of mitochondrial targeted antioxidants and free nitrates can improve vascular reactivity in those with PAD. Reduced endothelial reactivity may have deleterious effects for those with PAD during walking, since the endothelium dilates the arteries when shear increases at the onset of exercise, thereby highlighting a potential mechanism that may exacerbate exercise-induced ischemia. Interestingly, improvements in vascular reactivity mediated by mitochondrial derived antioxidants and free nitrates are paralleled by improvements in walking performance. This highlights the potential importance of ROS management in the treatment of those with PAD and may indicate an effective pharmacological target to improve vascular health and functional capacity in those with PAD.
A potentially effective pharmacological target for oxidative stress management in those with PAD may be the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) complex because NRF2 is directly involved in the cellular response to oxidative stress. Keap1 promotes the ubiquitination and destruction of intracellular NRF2, which keeps the concentration of NRF2 low in the cytosol under normal conditions. However, molecules that react with Keap1, such as reactive oxygen species, impede Keap1s ability to prevent NRF2 from accumulating. When NRF2 accumulates, it is translocated into the cell nucleus and acts as a transcription factor for several cellular antioxidants, which bind to molecules that cause oxidative stress, thereby reducing cellular oxidative damage. Therefore, substances that target the Keap1-NRF2 complex may be useful for reducing oxidative stress in those with PAD.
Of note, diroximel fumarate is a compound that directly interacts with the Keap1-NRF2 complex by its derivative monomethyl fumarate, and diroximel fumarate has been shown to reduce inflammation via this mechanism in those with multiple sclerosis. Therefore, the investigators postulate that diroximel fumarate may increase antioxidant capacity in those with PAD via the NRF2 mechanism, which may lead to improved endothelial function and walking capacity. However, there are currently no studies that have investigated the effects of acute diroximel fumarate intake on vascular function and walking capacity in individuals with PAD. Therefore, the investigators propose to test the hypothesis that acute exogenous diroximel fumarate intake will improve micro- and macro-vascular function, leg skeletal muscle mitochondrial function, and walking capacity in participants 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.
1,377 studies on the registry are indexed under Peripheral Arterial Disease; 275 are open to participants now.
This study's planned enrollment of 20 is below the median of 70 across 927 interventional studies indexed under Peripheral Arterial Disease.
Browse Peripheral Arterial Disease studies →University of Nebraska is the lead sponsor of 496 studies on the registry; 67 are open to participants now.
Of its 83 completed or terminated interventional studies of FDA-regulated products, 53 (64%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Peripheral artery disease (PAD) participants:
Complete blood count:
Age-matched control participants:
Complete blood count:
Exclusion Criteria:
Peripheral artery disease (PAD) participants:
Blood work and medical history NOT demonstrating:
Complete blood count NOT within ranges:
Age-matched control participants:
Complete blood count NOT within ranges:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive a single dose of VUMERITY (diroximal fumarate, 462mg). After a minimum period of 7 days, they will then receive a single dose of the placebo (microcrystalline cellulose, 462 mg).
Drug: Vumerity · Other: Placebo
Participants will receive a single dose of placebo (microcrystalline cellulose, 462 mg). After a minimum period of 7 days, they will then receive a single dose of VUMERITY (diroximal fumarate, 462mg).
Drug: Vumerity · Other: Placebo
Participants with peripheral artery disease (PAD) will receive a single dose of VUMERITY (diroximal fumarate, 462mg). After a minimum period of 7 days, they will then receive a single dose of the placebo (microcrystalline cellulose, 462 mg).
Drug: Vumerity · Other: Placebo
Participants with peripheral artery disease (PAD) will receive a single dose of placebo (microcrystalline cellulose, 462 mg). After a minimum period of 7 days, they will then receive a single dose of VUMERITY (diroximal fumarate, 462mg).
Drug: Vumerity · Other: Placebo
diroximal fumarate 462 mg (2 capsules)
Also known as: diroximal fumarate
Microcrystalline cellulose 462 mg (2 capsules)
Macrovascular Endothelial Function
Macrovascular endothelial function will be measured non-invasively using the flow-mediated dilation (FMD) technique in the brachial and popliteal arteries using a Doppler ultrasound. These measures will be performed before and after vumerity or placebo on the first visit, and these measures will be performed before and after Vumerity or placebo on the second visit.
Time frame: Day 1: before and after intervention. Day 7: before and after intervention.
Oxygen Transfer and Utilization
Oxygen transfer and utilization will be measured as the near-infrared spectroscopy (NIRS) reoxygenation rate in the medial gastrocnemius after an arterial occlusion. These measures will be performed before and after Vumerity or placebo on the first visit, and these measures will be performed before and after Vumerity or placebo on the second visit.
Time frame: Day 1: before and after intervention. Day 7: before and after intervention.
Femoral and Popliteal Artery Blood Flow
Femoral and popliteal artery blood flow will be measured in both legs using Doppler ultrasound. These measures will be performed before and after Vumerity or placebo on the first visit, and these measures will be performed before and after Vumerity or placebo on the second visit.
Time frame: Day 1: before and after intervention. Day 7: before and after intervention.
Walking capacity
Physical walking capacity will be measured during the Gardner treadmill protocol. Participants will walk on a treadmill at 2.0 miles per hour (mph). Grade will began at zero and will be increased by two percent every two minutes. Participants unable to walk at least 2.0 mph begin walking at 0.5 mph and their speed is increased by 0.50 mph every two minutes until the participant reaches 2.0 mph. After reaching 2.0 mph, treadmill grade is increased by two percent every two minutes. Participants are asked to continue walking without stopping until they cannot continue because of leg symptoms, exhaustion, or other symptoms. These measures will be performed before and after Vumerity or placebo on the first visit, and these measures will be performed before and after Vumerity or placebo on the second visit.
Time frame: Day 1: before and after intervention. Day 7: before and after intervention.
Circulating blood markers of Oxidative Stress and Antioxidants
Participants will have blood drawn from an antecubital vein to measure markers of redox balance (oxidants and antioxidants). These measures will be performed before and after Vumerity or placebo on the first visit, and these measures will be performed before and after Vumerity or placebo on the second visit.
Time frame: Day 1: before and after intervention. Day 7: before and after intervention.
Plan to share: No
Started Nov 2024 (actual). Primary completion is estimated for Dec 2026, 25 months after the start.
Of 26 phase 1 interventional studies under Peripheral Arterial Disease, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 9 and three quarters within 41. This study's planned 25 months is close to that.
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Studies of the drug tested here: Diroximel fumarate