Hepatocyte Growth Factor to Improve Functioning in PAD

The HI-PAD study will randomize 39 people age 55 and older with PAD who do not have critical
limb ischemia. The primary outcome is change in the six-minute walk distance at 3-month
follow-up after the first study drug injection. A secondary outcome in change in six-minute
walk distance at 6-month follow-up. Additional secondary outcomes are pain-free and maximal
treadmill walking distance, calf biopsy measures of skeletal muscle regeneration, capillary
density, and autophagy, and MRI-measured calf muscle perfusion at three-month follow-up.
Investigators will also measure change in six-minute walk distance at 12-month follow-up.

Inclusion Criteria:

- Age 55 or above

- Symptomatic PAD, defined as exertion-induced ischemic calf muscle symptoms during the
six-minute walk, during the baseline exercise stress test, or during daily walking
activities. PAD will be defined as an ankle brachial index (ABI) < or = 0.90 at the
baseline study visit or vascular lab evidence of PAD or angiographic evidence of
significant PAD.

Exclusion Criteria:

- Above- or below-knee amputation.

- Critical limb ischemia, including individuals with gangrene and lower extremity
ulcers.

- Wheelchair-bound or requiring a cane or walker to ambulate.

- Walking is limited by a symptom other than PAD.

- Lower extremity revascularization, orthopedic surgery, cardiovascular event, coronary
revascularization, or other major surgery in the previous three months and planned
revascularization or major surgery during the next six months.

- Major medical illness including renal disease requiring dialysis, lung disease
requiring oxygen, Parkinson's disease, or a life-threatening illness with life
expectancy less than six months. [NOTE: Participants who only use oxygen at night may
still qualify]

- History of cancer or incomplete cancer screening as recommended by the American Cancer
Society. Specifically, participants will be asked to provide documentation regarding
screening history for colon cancer and breast and cervical cancer (women). Screening
for colon cancer may consist of stool testing for blood in the past year. Men must
either provide documentation regarding prostate cancer screening history or indicate
after a telephone or in-person discussion with Dr. McDermott that they have elected to
decline prostate cancer screening. A chest computed tomography will be performed for
participants with >30 pack year history of smoking, unless they have not smoked within
the past 15 years, to screen for lung cancer that may exclude them. The study team may
also perform colon, breast, and/or cervical cancer screenings as part of study
participation. The study team will provide stool testing for blood for colon cancer
screening, mammogram for breast cancer screening, and a Pap test for cervical cancer
screening. Men who elect to have prostate cancer screening who have not had this
completed with their physician can have a prostate specific antigen (PSA) test
performed by study investigators. Participants who have a history of non-melanoma skin
cancer (i.e.had basal cell carcinoma or squamous cell carcinoma of the skin) may still
be eligible if the lesion was completely removed and there has been no evidence of
recurrence in the past year.

- Evidence of proliferative retinopathy.

- Positive test for Human Immunodeficiency Virus, hepatitis B virus, hepatitis C virus
or Human T-lymphotropic virus.

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

- Participation in or completion of a clinical trial in the previous three months.
[NOTE: after completing a stem cell or gene therapy intervention, participants will
become eligible after the final study follow-up visit of the stem cell or gene therapy
study so long as at least six months have passed since the final intervention
administration. After completing a supplement or drug therapy (other than stem cell or
gene therapy), participants will be eligible after the final study follow-up visit as
long as at least three months have passed since the final intervention of the trial.]

- Increase in angina or angina at rest.

- Premenopausal women.

- Non-English speaking.

- Visual impairment that limits walking ability.

- 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.

- Potential participants who have had symptoms from peripheral artery disease for less
than six months will be excluded.

- Potential participants who, after being advised of therapeutic options available for
people with PAD, prefer to return to their physician to discuss alternative treatment
(e.g. supervised exercise or revascularization). Potential participants may
participate in the study after 12 weeks has passed since their last supervised
exercise session or revascularization if they meet inclusion criteria.

- Potential participants with a baseline six-minute walk value < 595 or > 1,520 feet
will be excluded.

- Potential participants with the following laboratory values will be excluded: a
hemoglobin value < 8.0 g/dL, a white blood cell count < 3,000 cells per microliter,
platelet count < 75,000/mm3, GFR < 20 mL/minute/1.73 M2, AST or ALT value > 3 times
the upper limit of normal, or any other clinically significant laboratory abnormality
which, in the opinion of the investigator, should exclude the participant.

- Potential participants started on cilostazol within the past three months will be
excluded. They may be evaluated for eligibility once three months has passed since
beginning cilostazol.

- Vulnerable populations (fetuses, pregnant women, children, prisoners, and
institutionalized persons) and adults unable to consent will not be included in the
study.