Community Walking Exercise for Patients With Peripheral Artery Disease

The investigators will test the hypothesis that PAD patients randomized to the exercise
program in the community setting incorporating TMC+ will improve walking ability compared
with patients who receive the standard of care (exercise advice). Secondary hypotheses
include a significant improvement in patient-reported outcomes, an improvement in functional
ability or a significant increase in volume of physical activity for patients who complete
community-based walking exercise when compared with patients receiving the standard of care.
Exploratory hypotheses include a significant improvement in PWT for 1) patients receiving a
combination of lower extremity endovascular therapy (ET) and community-based walking exercise
or 2) open peripheral intervention and community-based walking exercise compared to patients
who do not receive endovascular therapy or open intervention and receive only the standard of
care.

Inclusion Criteria:

- Men and women diagnosed with atherosclerotic PAD

- ≥40 years of age

- An abnormal ankle-brachial index (ABI) of ≤.90

- For patients with an ABI >.90 and <1.00, a post-exercise ABI drop of 15% or more
compared to the resting ABI

- Patients receiving lower extremity ET or peripheral open intervention

- Patients not receiving lower extremity ET or peripheral open intervention but present
with stable claudication and an abnormal ABI

Exclusion Criteria:

- Lower extremity amputation(s), including a toe amputation, which interfere (s) with
walking on the treadmill

- Individuals with critical limb ischemia defined by ischemic rest pain or ischemic
ulcers/gangrene on the lower extremities

- PAD of non-atherosclerotic nature (e.g., fibromuscular dysplasia, irradiation,
endofibrosis)

- Coronary artery bypass grafts or major surgical procedures within 6 months prior to
screening

- Individuals whose walking exercise is primarily limited by symptoms of chronic
obstructive pulmonary disease, angina, or heart failure

- Individuals who are unable to walk on the treadmill at a speed of at least 2 mph for
at least 1 minute

- Individuals who have had a myocardial infarction within 3 months prior to screening

- Individuals who demonstrate symptoms consistent with acute coronary syndrome

- Individuals who exhibit ischemia as documented on the 12-lead electrocardiogram
including horizontal or down-sloping ST-segment depression ≥0.5 mm at rest and >1 mm
with exercise in 2 contiguous leads, relative to the PR-segment (ST-segment measured
0.08 seconds after the J point, ST-segment elevation ≥1 mm)

- Individuals who have had a transient ischemic attack or stroke 3 months prior to
screening

- Individuals with left bundle branch block or sustained ventricular tachycardia (>30
sec) during screening

- Individuals with uncontrolled hypertension (≥180 systolic or ≥100 diastolic resting
blood pressure) during screening

- Treatment with pentoxifylline or cilostazol for the treatment of claudication 4 weeks
prior to screening; Patients can be reconsidered for study inclusion following a 1
month washout period from these medications

- Electrolyte abnormalities (e.g., potassium <3.3 mmol∙Lˉ1 )

- Pregnancy, fertility without protection against pregnancy (for women of childbearing
potential, a serum pregnancy test will be performed at screening)

- Incarcerated individuals

- Individuals acutely impaired by alcohol or other illicit drugs

- Poorly controlled diabetes defined as glycated hemoglobin >12%

- Severely anemic patients (Hgb <11 g∙dLˉ1 for women and <10 g∙dLˉ1 for men)

- For patients who have not received peripheral revascularization, an ABI of >0.90

- For patients with equivocal resting ABIs (0.91-0.99), a drop of <15% in the
post-exercise ABI

- For individuals with non-compressible vessels (ABI >1.39) who have a toe- brachial
index (TBI) >0.70

- Inability to speak English

- Other clinically significant disease that is, in the opinion of the study team, not
stabilized or may otherwise confound the results of the study