Intermittent Pneumatic Compression With and Without Exercise to Improve Functioning in Peripheral Artery Disease

Walking exercise is first-line therapy for PAD. However, many PAD patients are unable or
unwilling to exercise. Therefore, in people with PAD, the investigators will determine
whether intermittent pneumatic compression augments the benefits of exercise and whether
intermittent pneumatic compression alone improves walking performance compared to sham
control. The investigators will conduct a randomized trial (2 x 2 factorial design) of 230
PAD participants randomized to one of four groups: Group A: intermittent pneumatic
compression + exercise; Group B: intermittent pneumatic compression+ "no exercise" control;
Group C: sham control + exercise; and Group D: sham control + "no exercise" control. The
intermittent pneumatic compression and sham interventions will be delivered for six months.
The primary outcome is change in six-minute walk distance at 6-month follow-up. In secondary
aims, the investigators will determine whether the benefits of intermittent pneumatic
compression persist even after intermittent pneumatic compression is discontinued and
delineate mechanisms by which intermittent pneumatic compression affects walking performance,
by measuring changes in MRI-measured calf muscle perfusion and physical activity. The
investigators will determine whether intermittent pneumatic compression improves systemic
endothelial function, by measuring changes in brachial artery flow-mediated dilation (FMD).

Inclusion Criteria:

All participants will have PAD, defined as an ankle-brachial index (ABI) < or = 0.90 at the
baseline study visit

Exclusion Criteria:

1. Above- or below-knee amputation.

2. Critical limb ischemia or ABI < 0.30.

3. Wheelchair-bound.

4. Current foot ulcer on bottom of foot.

5. Walking is primarily limited by a symptom other than PAD.

6. Failure to successfully complete the study run-in.

7. Major surgery, revascularization, or orthopedic surgery in the past 3 months or
planned in the next 12 months.

8. Major medical illness including Parkinson's Disease, renal disease requiring dialysis,
lung disease requiring oxygen, cancer requiring treatment in the previous two years,
or life-threatening illness with a life expectancy of less than six months.
Participants who only use oxygen at night will be potentially eligible. [NOTE:
potential participants treated for cancer in the past two years may still qualify if
they have had treatment for early stage cancer in the past two years and the prognosis
is excellent. Potential participants treated for basal cell or squamous cell skin
cancer will not be excluded.]

9. Already exercising at a level consistent with exercise intervention. Current or recent
participation in exercise rehabilitation (within the past six months).

10. Recently diagnosed (within the past three months) with acute lower extremity deep
venous thrombosis, pulmonary embolism, or severe heart failure (i.e. New York Heart
Association (NYHA) Class III or IV).

11. Mini-Mental Status Examination (MMSE) score <23 or dementia.

12. Participation in or completion of a clinical trial in the previous three months.

13. Non-English speaking.

14. Increase in angina in the past month, angina at rest,or abnormal baseline treadmill
stress test. Potential participants may become eligible following an abnormal baseline
treadmill stress test if they have evidence of an absence of coronary ischemia based
on testing with their own physician and if they do not have symptoms of unstable
angina.

15. Ongoing infection of the toes, foot, or lower extremity or cellulitis

16. Potential participants who started on cilostazol within the last three months. They
may be evaluated for eligibility once three months have passed since beginning
cilostazol.

17. Significant peripheral edema, defined as 3+ or greater edema severity, as determined
by the principal investigator.

18. BMI >40

19. In addition to the above criteria, investigator discretion will be used to determine
if the trial is unsafe or not a good fit for the potential participant.