The Role of microRNA-210 in Regulating Oxidative Stress in Patients With PAD

Study Overview
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Brief Summary
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MicroRNA-210 (miR-210) can be a potential therapeutic target of patients with peripheral artery disease (PAD). Recent evidence suggests the role of miR-210 and oxidative stress in the pathophysiology of PAD and its association with mitochondrial function, oxidative metabolism, walking distances and quality of life. The protocol evaluates the mechanisms which miR-210 regulates oxidative stress and provides evidence of potential therapeutic strategies.

Detailed Description
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The investigators will randomize 180 PAD patients that undergoing a revascularization operation in two groups: (1) an endovascular procedure or (2) an open bypass procedure. They are also planning to recruit 50 non-PAD healthy control subjects. The goal is to answer the main hypothesis that miR-210 gene expression is a master regulator of oxidative stress and is associated with mitochondrial dysfunction, oxidative metabolism, walking function and quality of life.

Official Title
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The Role of microRNA-210 in Regulating Oxidative Stress in Patients With Peripheral Artery Disease

Conditions
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Peripheral Arterial Disease, Vascular Diseases, Peripheral, Arterial Occlusive Diseases, Atherosclerosis

Intervention / Treatment
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* Procedure: Revascularization operation
* Other: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female 30 years or older, Infrainguinal PAD, critical limb ischemia, defined as arterial insufficiency with gangrene, nonhealing ischemic ulcer, or rest pain consistent, candidate for both endovascular and open infra-inguinal revascularization as judged by the vascular surgeons, absence of musculoskeletal (most commonly arthritis related) or neurologic (most commonly back pain and sciatica related) symptoms, willingness to comply with protocol, attend follow-up appointments, complete all study assessments, and provide written informed consent. Exclusion Criteria: life expectancy of less than 2 years due to reasons other than PAD, acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma, current chemotherapy or radiation therapy

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Revascularization group<br>Participants will be randomized to either an endovascular or an open bypass procedure. | Procedure: Revascularization operation<br>* Participants will be randomized into an endovascular or open bypass procedure.<br>|
| Other: Control group<br>Healthy non-PAD participants will be recruited as control group | Other: Control group<br>* Healthy non-PAD participants will be recruited for the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| miR-210 gene expression | Measure miR-210 gene expression at baseline and after intervention | Change from baseline to six-month follow-up | 
| Calf muscle biopsy biochemical measures | A skeletal muscle sample will be obtained from the gastrocnemius muscle. | Change from baseline to six-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six-minute walk performance | Participants walking up and down a 100 foot hallway for six minutes following a standardized protocol. The goal is for them to walk as far as possible in six minutes | Change from baseline to six-month follow-up | 
| Graded treadmill walk performance | Participants walking on treadmill following a standardized protocol. The goal is for them to walk as far as possible while the treadmill incline increases every 2 minutes. | Change from baseline to six-month follow-up | 
| The 36-Item Short Form questionnaire (SF-36) | This well validated quality of life measure will be used to assess changes in patient perceived quality of life. The SF-36 is scored from 0-100, with 100 being the best score. | Change from baseline to six-month follow-up | 
| The Walking Impairment Questionnaire | The well validated Walking Impairment Questionnaire (WIQ) will be used to measure patient- perceived walking performance. The WIQ is scored from 0-100, with 100 being the best score. | Change from baseline to six-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral artery disease, microRNA