Effects of a medication on blood vessel function and walking ability in people with peripheral artery disease

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

This study is testing if a medication called diroximel fumarate can help improve blood vessel function and walking ability in people aged 50-75 with peripheral artery disease.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 50 Years to 75 Years
• Sex: All
• Sponsor: University of Nebraska (other)
• Locations: 1 site (Omaha, Nebraska)
• Trial ID: NCT06319339 on ClinicalTrials.gov

What this trial studies

This study investigates the impact of diroximel fumarate (Vumerity) on improving vascular function and walking capacity in individuals with peripheral artery disease (PAD). Participants aged 50-75 with diagnosed PAD will receive either the medication or a placebo, and their vascular function will be assessed through various tests, including flow-mediated dilation and arterial stiffness measurements. The study aims to reduce oxidative stress and enhance endothelial reactivity, which is crucial for improving exercise tolerance in PAD patients.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 50-75 with a diagnosis of Fontaine stage II-III peripheral artery disease and a history of exercise-induced claudication.

Not a fit: Patients with severe renal or hepatic dysfunction, or those outside the specified age range, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved walking capacity and quality of life for patients suffering from peripheral artery disease.

How similar studies have performed: While the approach of using diroximel fumarate in this context is novel, previous studies have shown that antioxidant therapies can improve vascular function in similar patient populations.

Eligibility criteria

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 this trial is running

Omaha, Nebraska

• University of Nebraska - Omaha — Omaha, Nebraska, United States (RECRUITING)

Study contacts

• Principal investigator: Song-Young Park, PhD — University of Nebraska
• Study coordinator: Song-Young Park, PhD

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