Clinical trial NCT03363165: Hepatocyte Growth Factor to Improve Functioning in PAD
Official title: Hepatocyte Growth Factor to Improve Functioning in Peripheral Artery Disease: The HI-PAD Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral Artery Disease
Keywords: PAD
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Helixmith Co., Ltd.
First posted: 2017-12-06
Enrollment: 39
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: HI-PAD is a placebo controlled double-blind randomized pilot clinical trial to determine whether VM202 may improve walking ability in people with lower extremity peripheral artery disease (PAD).

Detailed description: 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 6-month follow-up after the first study drug injection. A secondary outcome in change in six-minute walk distance at 3-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.

Eligibility criteria: 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 within the last 5 years 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), according to the American Cancer Society guidelines. 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 55 to 74 years old 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 according to the participant's eligibility for these screening tests, using the American Cancer Society guidelines. 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. Participants who were treated for retinopathy at least 5 years prior to their baseline assessment who do not have evidence of proliferative retinopathy at the time of baseline assessment may still be eligible.
* Positive test for active Human Immunodeficiency Virus (HIV), hepatitis B virus, hepatitis C virus or Human T-lymphotropic virus. Patients who have positive antibodies for HIV, hepatitis B, or hepatitis C who do not have detectable viral load will be eligible for participation.
* 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. Participants may undergo a serum electrophoresis and an immunofixation blood test if indicated to further evaluate abnormalities on the complete blood count if needed to assess study eligibility.
* 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.

Primary outcomes:
measure: Six-minute Walk Distance
timeFrame: Change from baseline to six-month follow-up in six-minute walk distance
Secondary outcomes:
measure: Maximal Treadmill Walking Time
timeFrame: Change from baseline to three-month follow-up
measure: Calf Muscle Perfusion
timeFrame: Change from baseline to three-month follow-up
measure: Calf Muscle Biopsy Biochemical Measures (Satellite Cells - Total SCs/100 Fibers)
timeFrame: Change from baseline to three-month follow-up
measure: Walking Impairment Questionnaire - Distance Score
timeFrame: Change from baseline to three-month follow-up
measure: The Short-Form-36 Physical Functioning Score
timeFrame: Change from baseline to three-month follow-up
measure: The Short-Form-36 Physical Functioning Score
timeFrame: Change from baseline to six-month follow-up
measure: Walking Impairment Questionnaire - Distance Score
timeFrame: Change from baseline to six-month follow-up
measure: Six-minute Walk Distance
timeFrame: Change in six-minute walk distance from baseline to three-month follow-up
measure: Pain-free Treadmill Walking Time
timeFrame: Change from baseline to three-month follow-up
Other outcomes:
measure: Six-minute Walk Distance
timeFrame: Change from baseline to 12-month follow-up in six minute walk distance.
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: Mary McDermott, MD
role: PRINCIPAL_INVESTIGATOR
References: