Peripheral Artery DiseasePhase 2HI-PADNCT03363165
Hepatocyte Growth Factor to Improve Functioning in PAD
A Phase 2 study testing VM202 in people with Peripheral Artery Disease, run by Northwestern University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Peripheral Artery Disease
- What is being tested?
- VM202
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2018to 5 Sep 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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]
Show all 22Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hepatocyte Growth Factor to Improve Functioning in Peripheral Artery Disease: The HI-PAD Study
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).
Read the 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.
- Conditions
- Peripheral Artery Disease
- Being tested
- VM202, Placebo
- Keywords
- PAD
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VM202Drug
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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Change from baseline to six-month follow-up in six-minute walk distance
Secondary outcomes (9)
Maximal Treadmill Walking Time
A Gardner or Modified Gardner treadmill exercise protocol will be used
Measured: 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
Measured: Change from baseline to three-month follow-up
Calf Muscle Biopsy Biochemical Measures (Satellite Cells - Total SCs/100 Fibers)
A skeletal muscle sample will be obtained from the calf muscle. The outcome is the number of satellite cells per 100 muscle fibers
Measured: Change from baseline to three-month follow-up
Walking Impairment Questionnaire - Distance Score
The well validated Walking Impairment Questionnaire will be used to measure patient- perceived walking performance. The WIQ is scored from 0-100, with 100 being the best score. We will use distance and speed sub-components separately.
Measured: Change from baseline to three-month follow-up
The Short-Form-36 Physical Functioning Score
This well validated quality of life measure will be used to assess changes in patient perceived quality of life. The SF-36 is scored from 0-100, with 100 being the best score.
Measured: Change from baseline to three-month follow-up
The Short-Form-36 Physical Functioning Score
This well validated quality of life measure will be used to assess changes in patient perceived quality of life. Scored on a 0-100 scale, where 100- is best.
Measured: Change from baseline to six-month follow-up
Walking Impairment Questionnaire - Distance Score
The well validated Walking Impairment Questionnaire will be used to measure patient- perceived walking performance.
Measured: Change from baseline to six-month follow-up
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
Measured: Change in six-minute walk distance from baseline to three-month follow-up
Pain-free Treadmill Walking Time
A Gardner or Modified Gardner treadmill exercise protocol will be used
Measured: Change from baseline to three-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2017
- Study start1 Jan 2018
- Primary completion10 Feb 2023
- Study completion5 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Peripheral Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA), Helixmith Co., Ltd.
- Responsible party
- Principal investigator, Mary McDermott, Northwestern University
- Investigators
- Mary McDermott, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03363165
- Sponsor's protocol ID
- STU00205511
- Other IDs
- R21AG056903
- Acronym
- HI-PAD
- Status last verified
- May 2024
- First submitted
- 30 Nov 2017
- Last updated
- 30 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39778757Nayak 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.
PubMed 36588397
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatocyte Growth Factor to Improve Functioning in Peripheral Artery Disease: The HI-PAD Study
- ClinicalTrials.gov ID
- NCT03363165
- Acronym / sponsor ID
- HI-PAD / STU00205511
- Conditions
- Peripheral Artery Disease
- Keywords
- PAD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA), Helixmith Co., Ltd.
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 10 Feb 2023 (actual)
- Study completion
- 5 Sep 2023 (actual)
- First posted
- 6 Dec 2017 (actual)
- Results
- Posted 30 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VM202 | Active comparator | Drug: VM202Participants will receive injections of VM202 (4 mgs) in calf skeletal muscle every 14 days for a total of four treatment days. |
| Placebo | Placebo comparator | Other: PlaceboParticipants will receive injections of placebo in calf skeletal muscle every 14 days for a total of four treatment days. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VM202Participants 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. | Drug | VM202 |
| PlaceboParticipants 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. | Other | Placebo |
Primary outcome
Six-minute Walk Distance
Time frame: Change from baseline to six-month follow-up in 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
9 secondary outcomes
Maximal Treadmill Walking Time
Time frame: Change from baseline to three-month follow-up
Calf Muscle Perfusion
Time frame: Change from baseline to three-month follow-up
Calf Muscle Biopsy Biochemical Measures (Satellite Cells - Total SCs/100 Fibers)
Time frame: Change from baseline to three-month follow-up
Walking Impairment Questionnaire - Distance Score
Time frame: Change from baseline to three-month follow-up
The Short-Form-36 Physical Functioning Score
Time frame: Change from baseline to three-month follow-up
The Short-Form-36 Physical Functioning Score
Time frame: Change from baseline to six-month follow-up
Walking Impairment Questionnaire - Distance Score
Time frame: Change from baseline to six-month follow-up
Six-minute Walk Distance
Time frame: Change in six-minute walk distance from baseline to three-month follow-up
Pain-free Treadmill Walking Time
Time frame: Change from baseline to three-month follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39778757McDermott 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.
- Derived from this study: PubMed 36588397Nayak 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary McDermott, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VM202 in people with Peripheral Artery Disease, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Six-minute Walk Distance (time frame: Change from baseline to six-month follow-up in six-minute walk distance). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03363165, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2024.