Hepatocyte Growth Factor to Improve Functioning in PAD | NCT03363165

ID	Type	Description	Link
R21AG056903	U.S. NIH Grant/Contract		View source

Name	Class
National Institute on Aging (NIA)	NIH
Helixmith Co., Ltd.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
VM202	Active Comparator	Participants will receive injections of VM202 (4 mgs) in calf skeletal muscle every 14 days for a total of four treatment days.	Drug: VM202
Placebo	Placebo Comparator	Participants will receive injections of placebo in calf skeletal muscle every 14 days for a total of four treatment days.	Other: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
VM202	Drug	Participants randomized to VM202 will receive calf muscle injections of VM202 to each leg with evidence of PAD. Injections of VM202 are administered by a physician in a double-blinded fashion after randomization on Day 0, Day 14, Day 28, and Day 42, for a total of four treatment days. Therefore, participants randomized to VM202 will receive 4 mgs of VM202 in each calf muscle on each treatment day. Injections are placed beginning 2 cm below the popliteal crease, and are administered in a pre-designed sequence and pattern, at a measured distance 2 cm apart. Note: Participants who have a evidence of PAD in only one leg will only receive injections in the leg with evidence of PAD.

Measure	Description	Time Frame
Six-minute Walk Distance	Participants walking up and down a 100 foot hallway for six minutes following a standardized protocol. The goal is for them to walk as far as possible in six minutes	Change from baseline to six-month follow-up in six-minute walk distance

Measure	Description	Time Frame
Maximal Treadmill Walking Time	A Gardner or Modified Gardner treadmill exercise protocol will be used	Change from baseline to three-month follow-up
Calf Muscle Perfusion	Calf muscle perfusion is measured by Magnetic Resonance Imaging (MRI) Unit of measure is ml/minute per 100 gms tissue

Measure	Description	Time Frame
Six-minute Walk Distance	See above regarding 6-minute walk protocol	Change from baseline to 12-month follow-up in six minute walk distance.

Eligibility Module

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.

Name	Affiliation	Role
Mary McDermott, MD	Northwestern University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Northwestern University		Chicago	Illinois	60611	United States

PubMed Identifier	Type	Citation	Retractions
39778757	Derived	McDermott MM, Sufit R, Domanchuk KJ, Volpe NJ, Kosmac K, Peterson CA, Zhao L, Tian L, Zhang D, Xu S, Ismaeel A, Ferrucci L, Parekh ND, Lloyd-Jones D, Kramer CM, Leeuwenburgh C, Ho K, Criqui MH, Polonsky T, Guralnik JM, Kibbe MR. Hepatocyte growth factor for walking performance in peripheral artery disease. J Vasc Surg. 2025 Jun;81(6):1467-1478.e1. doi: 10.1016/j.jvs.2024.12.124. Epub 2025 Jan 6.
36588397	Derived	Nayak P, Polonsky T, Tian L, Greenland P, Xu S, Zhang D, Zhao L, Criqui MH, Kibbe MR, Gladders B, Goodney P, Ho K, Guralnik JM, McDermott MM. Medical therapies, comorbid conditions, and functional performance in people with peripheral artery disease enrolled in clinical trials between 2004 and 2021. Vasc Med. 2023 Apr;28(2):144-146. doi: 10.1177/1358863X221145533. Epub 2023 Jan 1.

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants will receive injections of placebo in calf skeletal muscle every 14 days for a total of four treatment days. Placebo: Participants randomized to placebo will receive calf muscle injections of placebo (the excipient buffer formulation minus the VM202) to each leg with evidence of PAD. Injections of placebo are administered by a physician in a double-blinded fashion after randomization on Day 0, Day 14, Day 28, and Day 42, for a total of four treatment days. Placebo appears identical to the VM202 study drug and is administered in a pattern on the calf identical to that of the VM202 injections. Note: Participants who have a evidence of PAD in only one leg will only receive injections in the leg with evidence of PAD.
FG001	VM202	Participants will receive injections of VM202 (4 mgs) in calf skeletal muscle every 14 days for a total of four treatment days. VM202: Participants randomized to VM202 will receive calf muscle injections of VM202 to each leg with evidence of PAD. Injections of VM202 are administered by a physician in a double-blinded fashion after randomization on Day 0, Day 14, Day 28, and Day 42, for a total of four treatment days. Therefore, participants randomized to VM202 will receive 4 mgs of VM202 in each calf muscle on each treatment day. Injections are placed beginning 2 cm below the popliteal crease, and are administered in a pre-designed sequence and pattern, at a measured distance 2 cm apart. Note: Participants who have a evidence of PAD in only one leg will only receive injections in the leg with evidence of PAD.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	VM202	Participants will receive injections of VM202 (4 mgs) in calf skeletal muscle every 14 days for a total of four treatment days. VM202: Participants randomized to VM202 will receive calf muscle injections of VM202 to each leg with evidence of PAD. Injections of VM202 are administered by a physician in a double-blinded fashion after randomization on Day 0, Day 14, Day 28, and Day 42, for a total of four treatment days. Therefore, participants randomized to VM202 will receive 4 mgs of VM202 in each calf muscle on each treatment day. Injections are placed beginning 2 cm below the popliteal crease, and are administered in a pre-designed sequence and pattern, at a measured distance 2 cm apart. Note: Participants who have a evidence of PAD in only one leg will only receive injections in the leg with evidence of PAD.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Six-minute Walk Distance

Participants walking up and down a 100 foot hallway for six minutes following a standardized protocol. The goal is for them to walk as far as possible in six minutes

Posted

Mean

Standard Error

meters

Change from baseline to six-month follow-up in six-minute walk distance

ID	Title	Description
OG000	Placebo	Participants will receive injections of placebo in calf skeletal muscle every 14 days for a total of four treatment days. Placebo: Participants randomized to placebo will receive calf muscle injections of placebo (the excipient buffer formulation minus the VM202) to each leg with evidence of PAD. Injections of placebo are administered by a physician in a double-blinded fashion after randomization on Day 0, Day 14, Day 28, and Day 42, for a total of four treatment days. Placebo appears identical to the VM202 study drug and is administered in a pattern on the calf identical to that of the VM202 injections. Note: Participants who have a evidence of PAD in only one leg will only receive injections in the leg with evidence of PAD.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants will receive injections of placebo in calf skeletal muscle every 14 days for a total of four treatment days. Placebo: Participants randomized to placebo will receive calf muscle injections of placebo (the excipient buffer formulation minus the VM202) to each leg with evidence of PAD. Injections of placebo are administered by a physician in a double-blinded fashion after randomization on Day 0, Day 14, Day 28, and Day 42, for a total of four treatment days. Placebo appears identical to the VM202 study drug and is administered in a pattern on the calf identical to that of the VM202 injections. Note: Participants who have a evidence of PAD in only one leg will only receive injections in the leg with evidence of PAD.

ID	Term
D050197	Atherosclerosis
D001161	Arteriosclerosis
D001157	Arterial Occlusive Diseases
D014652	Vascular Diseases