Low InTensity Exercise Intervention in PAD

We will randomize 305 PAD participants to one of three parallel arms: Group 1:
Low-intensity, self-paced walking exercise; Group 2: Standard high intensity, ischemic
pain-inducing walking exercise; Group 3: Non-exercising attention control group. The low and
high intensity exercise groups will attend center-based exercise sessions once per week for
four weeks followed by transition to an entirely home-based exercise program for an
additional 48 weeks (52 weeks total). The low and high intensity exercise interventions will
use identical self-regulatory and support strategies. However, the low intensity exercise
group will be instructed to exercise with minimal to no ischemic leg discomfort and the high
intensity group will be instructed to exercise to maximal ischemic leg pain. These two
distinct exercise prescriptions will be reinforced during 48 weeks of home-based exercise,
using a well-validated behavioral coaching model that can be delivered by telephone once
weekly. Our primary outcome is change in six-minute walk distance at 52-week follow-up. If
our hypotheses are correct, millions of people with PAD will benefit from this alternative
exercise regimen which will be accessible to most of the 8 million people in the U.S. who
suffer from PAD.

Inclusion Criteria:

1. An ABI < or = 0.90 is a well accepted standard for the diagnosis of PAD and will be
our inclusion criterion

2. People with an ABI of 0.91-1.00 who experience a 20 % ankle systolic pressure drop
after the heel-rise test will also be included.

Exclusion Criteria:

1. Above or below knee amputation, critical limb ischemia, wheelchair confinement, or
foot ulcer.

2. Individuals whose walking is limited by a condition other than PAD.

3. > Class II NYHA heart failure or angina. Increase in angina, angina at rest, or
abnormal baseline treadmill stress test.

4. Major surgery including lower extremity revascularization or orthopedic surgery
during the prior three months or anticipated in the next twelve months.

5. Major medical illness including renal disease requiring dialysis, lung disease
requiring oxygen, or cancer requiring treatment in the prior three years.

6. Mini-mental status examination score <23 (61), dementia, or psychiatric illness
including severe depression or anxiety.

7. Currently walking regularly for exercise.

8. Current or recent (within 3 months) participation in another clinical trial or
cardiac rehabilitation.

9. Current or recent participation in a stem cell or gene therapy clinical trial where
the final intervention administration is within 6 months screening.

10. Chronic pain syndrome requiring narcotics.

11. Individuals with PAD, a prior history of lower extremity revascularization and have a
normal ABI.

12. Individuals who are not able to walk at 1.0 MPH on a treadmill for two minutes.

13. Individuals with PAD who do not experience exertional leg symptoms during both the
six minute walk and the treadmill stress test. To be included, participants must
experience leg symptoms during either the six minute walk or the treadmill stress
test.