June 28, 2017
VASCSTIM CLINICAL PROTOCOL
Peripheral arterial disease (PAD) is a major cause of morbidity and mortality. Recent data has shown that it has become the leading cause of hospital readmission and results in XXX,000 amputations each year. The most common cause of PAD is diabetes, which can cause conduit vessel disease, but more commonly results in occlusion of the microvasculature. This microvascular form of PAD, is not very responsive to current surgical or catheter based revascularization therapy. It typically results in non-healing ulcers once a skin breakdown occurs, despite the use of several current treatment options including hyperbaric oxygen and various dressings. Non-healing ulcers results in significant morbidity, but also significant health care costs which have been recently estimated at over $xx million/year.
These data provide the stimulus for identification of new treatment options. Two of the most promising are use of low current Bioelectric Stimulation (BES) and amniotic fluid and membranes(AF) in patients with or without the diagnosis of diabetes.
The goal of this registry is to document the ability of the combination of BES and AF in improve the size and depth of non-healing ulcers due to PAD.
Description: This is a prospective, non-randomized, non-blinded, interventional, consecutive series Registry study to determine initial safety and efficacy of a series of treatments with bioelectric stimulation controlled protein expression followed by use of AF as a membrane laid onto the ulcer, with or without additional use of injected AF around the ulcer in the treatment of non-healing skin ulcers of leg or foot due to PAD.
The study, including the protocol and consent form will have been approved without stipulations by a local or certified Institutional Review Board as meeting safe and good clinical practice before any subject will be enrolled.
- Age 18-80 yrs of age
- Non-healing skin ulcer of leg or foot > 2 cm in diameter
- Able to tolerate up to 40 minutes of BES on the non-involved leg or foot
- Able and willing to make the required study visits.
- Able and willing to give informed consent and follow study instructions.
- Must speak, read, and understand English
- Agree to allow photographs to be taken of the ulcer before and at the end of the treatment period to document change.
- Use of concomitant treatments to improve wound healing, including topical medications, oral medications, hyperbaric oxygen therapy, non-ablative fractional laser treatment, low-level laser therapy, PRP injection within the preceding 2 months.
- Allergic to lidocaine or epinepherine
- Planned revascularization procedure in next 3 months
- Individuals with diminished decision-making capacity
- Renal replacement therapy
- Pregnancy or lactating period for females
Target Number of Participants: 300
Target Number of Enrolling Sites: 30
Any subject with a non-healing ulcer of >2 cm in diameter who meet all Inclusion and Exclusion criteria will be eligible for participation. Each potential subject will have a brief history and examination performed by the Investigator, and if acceptable, will be provided with an overview of the Registry and then provided with the Consent Form. If they choose to participate, and sign the Consent form, they will be enrolled in the Registry.
All potential enrollees will have been evaluated by a certified vascular surgeon or physician who stipulates that the patient has a significant ulcer of the foot or leg is not responsive to all common treatments.
Before the procedure, a baseline photo will be taken of the planned treatment ulcer to compare to the measurements at the end of treatment period of 12 weeks.
Screening Treatment Bioelectic Stimulator:
All participants will have two standard electrical conductive skin patches or electro acupuncture needles applied in the region near the ulcer and connected to a bioelectric stimulation signal generator that has been previously tested and proven to be capable of delivering the required current.
The stimulator is capable of transmitting specific signals will be applied first to the uninvolved leg or foot. It will run through up to a 40 minute cycle of protein release signals to stimulate the release/increased expression of a number of growth factors that have been extensively shown to stimulate both the growth of new blood vessels and recruitment of stem cells to enhance native wound healing, initially including: SDF-1, and transitioning through IGF-1, HGF, EGF, eNOS, VEGF, Follistatin, Tropoelastin, and Activin A+B. If well tolerated, the patient will be eligible to participate in the Registry and treatment of the involved leg or foot.
Treatment with Amniotic Membrane with or without Amniotic Fluid (AF) Injection:
Each patient enrolled in the Registy will receive a single covering of the ulcer with an appropriate sized Amniotic Fluid Membrane, which will be provided by Bioleonhardt VASCSTIM, and reconstituted with several cc’s of Amniotic Fluid and laid directly onto the ulcer/wound.
The decision to also inject up to 5 cc’s of Amniotic Fluid will be made by the patient’s vascular surgeon or physician in advance of the treatment and injected at equal spacing into 8-10 sites approximately 2-3 centimeters from the edge of the wound in a circumferential pattern, with or without the use of lidocaine anesthesia at the patient’s choice.
A non-adhesive dressing will be applied over the Amniotic Membrane and wound at the completion of this treatment and a fresh dressing maintained over the wound for a minimum of 10 days, and then may remain uncovered at the discretion of the treating physician/
The treatments will take place for a period of 40 minutes, 3 times/week for 12 weeks to demonstrate the safety and benefit of the planned therapy.
Follow Up Evaluations:
At the end of 6 and 12 weeks, a photo will be taken of the wound being treated to measure and document the response to treatment.
The goal is complete healing of the wound by the end of the treatment.
Each subject will also have a brief interview inquiring about any adverse effects noted by the subject since enrolling in the Rtudy, and an examination by the Principal Investigator for any adverse effects of the therapy including damage or injury.
Co-Primary Outcome Measure:
- Incidence of treatment-related adverse events by the end of the treatment period, to include, but not exclusively: local itching, bleeding, pain, swelling, local pain, or headache, visual changes, palpitations, or nausea, AND
- Percentage of wound healed by the end of the treatment period as assessed by quantitative measurement of the size of the wound.
Secondary Outcome Measures:
- Any adverse events not described above
- Incidence of need to terminate the study for pain or other cause
- Failure of the Bioelectric Stimulator
- Stopping Rules:
The Registry will be paused if a total of 3 of the study subjects experience a treatment-related side effect of at least moderate severity. It will be restarted when additional investigation yields a clear cause and effective action plan has been implemented.
Data will be collected for each patient and analyzed at three time points including the end of the first 100 patients, the end of 200 patients, and when the last enrolled individual has reached the 6 month post treatment time point. The Registry may be stopped if the data demonstrates a > 67 % complete wound healing at the end of the 12 week treatment period.
Additional subjects may be enrolled into the study if approved by the IRB and Sponsor.