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