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

Launched by UNIVERSITY OF NEBRASKA · Mar 18, 2024

Keywords

ClinConnect Summary

This clinical trial is exploring whether a medication called diroximel fumarate, also known as Vumerity, can help improve blood vessel function and walking ability in people with Peripheral Artery Disease (PAD). PAD is a condition that affects blood flow to the legs, often causing pain during exercise. The researchers believe that this medication may reduce harmful stress in the body and improve how well blood vessels respond during physical activity, which could help participants walk better and feel more comfortable during exercise.

To participate in this study, individuals need to be between 50 and 75 years old, postmenopausal, and diagnosed with moderate PAD that limits their walking. Participants will either receive the medication or a placebo (a harmless pill with no active ingredients) and will undergo several tests to measure changes in their blood vessel function and walking ability. This trial is currently recruiting participants, and those who qualify will have regular follow-ups to monitor their health and the effects of the treatment. If you or someone you know fits the criteria and is interested, this could be an opportunity to contribute to important research on improving PAD management.

Gender

ALL

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