Leg Thermotherapy for Intermittent Claudication

Peripheral arterial disease is characterized by atherosclerotic obstruction of the arteries
in the lower extremities and affects approximately 10% of individuals older than 65 years.
The most common clinical presentation of peripheral arterial disease is intermittent
claudication, defined as leg pain caused by insufficient blood flow during walking.
Individuals with intermittent claudication have severe exercise intolerance and markedly
reduced levels of daily ambulatory activity. It is estimated that up to 40 million people
worldwide suffer from intermittent claudication. Despite the increasing prevalence of this
condition, few medical therapies improve mobility and exercise tolerance in these patients.
An urgent need remains for the development of novel, non-invasive strategies that are more
widely accessible and eliminate the need for supervision and frequent traveling to a clinical
facility. The study proposes to evaluate the potential of leg thermotherapy as a
non-pharmacological intervention that could improve the mobility and exercise tolerance of
patients with intermittent claudication.

Subjects will complete baseline assessments for eligibility and ability to do study,
including medical history, quality of life assessment, ankle-brachial measurement, leg MRI,
venous blood draw, assessment of vascular function, and 6-minute walk test. Treatment
consists of 3 treatment sessions per week for six consecutive weeks. Subjects will be
randomized to low-heat therapy or high-heat therapy. Subjects will wear water-circulating
pants through which the heat therapy will be administered during the treatment sessions.
Outcome measurements (same as baseline assessments) will be repeated after 9 treatment
sessions and after 18 treatment sessions (at the end of the treatment period).

Inclusion Criteria:

- Men and women with a stable symptomatic claudication for ≥6 months

- Ankle brachial index <0.9

Exclusion Criteria:

- Uncontrolled Diabetes (HbA1C > 8.5 measured within 3 months prior to date of consent)

- Heart Failure

- Chronic Obstructive Pulmonary Disease

- Critical limb ischemia (ischemic rest pain or ischemia-related non healing wounds or
tissue loss

- Prior amputation

- Exercise-limiting comorbidity (i.e., angina, chronic lung disease, or arthritis)

- Recent (<3 months) infrainguinal revascularization (surgery or endovascular
revascularization) or revascularization planned during study period.

- Plans to change medical therapy during the duration of the study

- Active cancer

- Chronic kidney disease (eGFR <30 by Modification of Diet in Renal Disease or Mayo or
Cockcroft-Gault formula).

- HIV positive, active hepatitis B virus (HBV) or hepatitis C virus (HCV) disease.

- Presence of any clinical condition that in the opinion of the principal investigator
makes the patient not suitable to participate in the trial.

- Peripheral neuropathy, numbness, or paresthesia in the legs.

- Morbid obesity BMI > 35.

- Open wounds or ulcers on the extremity.

MRI Exclusions:

- Cardiac pacemaker

- Implanted cardiac defibrillator

- Aneurysm clips

- Carotid artery vascular clamp

- Neurostimulator

- Insulin or infusion pump

- Implanted drug infusion device

- Bone growth/fusion stimulator

- Cochlear, otologic, or ear implant

- History of claustrophobia or who are unable to lie flat or who do not fit inside the
bore of the scanner