Acute Effects of Leg Heating on Skeletal Muscle Blood Flow

Study Overview
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Brief Summary
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The purpose of this study is to apply local heat to the legs, thighs and buttocks of patients with peripheral arterial disease and use PET/CT imaging with an injectable stable radiotracer to study direct measurement of blood flow in the legs pre and post heat treatment.

Detailed Description
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Cilostazol is the only effective medication available to treat walking pain (intermittent claudication) and it has multiple side effects. Overall improvement in walking performance in patients who use cilostazol is small. Endovascular and surgical interventions are effective alternatives for patients who don't respond to medical therapy, however, these procedures are costly and only applicable to patients with certain lesions types and carry a high risk of restenosis. Heat therapy (HT) is an emerging non-invasive approach that has been shown to enhance vascular function of the leg in old individuals. The objective of this study is to test the hypothesis that a single session of heat therapy will increase local muscle tissue blood flow in the calf of patients with PAD as assessed by PET/CT imaging of generator-based 62Cu-ETS. Subjects who have met inclusion criteria will volunteer for a single experimental visit. Participants will wear the water circulating pants and asked to rest supine for 30 minutes inside the scanner. Water at 43 degrees C will be perfused through the pants for 90 minutes with the goal to increase skin temperature in the calf to 39 degrees C. IV injections of 62Cu-ETS and subsequent perfusion imaging will be performed at the end of the 30 minute baseline period, after 45 minutes of heat therapy and at the end of the intervention (90 minutes). Due to the short half life of 62Cu, radioactivity from the prior administrations will not interfere with acquisition of a subsequent PET scan at this timing interval.

Official Title
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Acute Effects of Leg Heating on Skeletal Muscle Blood Flow in Patients With Symptomatic Peripheral Artery Disease

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Device: Heat Therapy (HT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women with a stable symptomatic claudication for >/= 6 months Ankle brachial index < 0.9 Exclusion Criteria: Uncontrolled diabetes Heart failure COPD Critical limb ischemia Prior amputation Exercise-limiting co-morbidity Recent (< 3 months) intra-inguinal revascularization or planned in study period Plans to change medical therapy during duration of study Active cancer Chronic kidney disease (eGFR < 30) HIV positive, active HBV or HCV disease Presence of an clinical condition that makes the patient not suitable to participate in the trial Peripheral neuropathy, numbness or paresthesia in the legs Morbid obesity BMI > 36 or unable to fit into water-circulating pants Open wounds or ulcers on the extremity Claustrophobia/unable to tolerate PET/CT scanning Women of child-bearing age
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All of the subjects in this study will receive leg heat therapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heat Therapy<br>Subject will dress in water-circulating trousers that are connected to a Heat Therapy (HT) pump. Warm water (42-43 degrees C) will be perfused through the pants for 90 minutes. | Device: Heat Therapy (HT)<br>* Water at 42-43 degrees C will be circulated through the water circulating trousers to obtain calf skin temperature 39 degrees C followed by PET/CT imaging of generator-based 62Cu-ETS.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in calf blood flow | Calf muscle perfusion rate (mL⋅min-1⋅g-1) will be obtained after administration of tracer 62Cu-ETS before, during and after exposure to heat therapy or a control intervention. Changes from in perfusion rate from baseline to 45 minutes and 90 minutes of heating or control will be measured. | Blood flow measurements will be completed at baseline (0 minutes) and after 45 and 90 minutes of exposure to heat therapy or a control regimen |