Peripheral arterial disease (PAD) is a highly prevalent condition that is growing rapidly due to shifting demographics, affecting 202M people worldwide and 8.5M in the USA, with an annual growth rate of 6.8%. Approximately one-third of PAD patients experience lower extremity pain that limits activity, and one-third of these patients suffer from critical limb ischemia (CLI), which lacks any effective treatment option and is associated with devastating complications including resting pain, skin ulcers, and gangrene, often requiring amputation. Invasive surgical or catheter-based treatments are ineffective in CLI and associated with complications and up to 40% rate of long-term restenosis. Acoustic energy modalities have been shown to promote collateral vessel growth, angiogenesis, and to improve perfusion in animal models of coronary artery disease (CAD) and PAD, with promising early human data in CAD. Vibrato Medical is developing a groundbreaking new treatment with the first wearable therapeutic ultrasound (TUS) device for the non-invasive, outpatient treatment of PAD that promotes collateral vessel growth and angiogenesis, and restores perfusion. The VibratoSleeve is a disruptive, paradigm-shifting device that will fundamentally alter the PAD/CLI treatment landscape with a non-invasive, wearable, outpatient treatment that will prevent amputations, hospitalizations and other complications of advanced PAD. The goal of this NIH Phase 1 SBIR proposal is to model, fabricate and acoustically verify a phased array transducer sleeve to treat the posterior tibial angiosome. In Aim 1, Vibrato will perform acoustic modeling and simulation of TUS transducer arrays to identify the optimal transducer frequency, size, number and configuration to optimize acoustic delivery to the posterior tibial angiosome. Based on results from Aim 1, Vibrato will partner with PiezoTechnologies for Aim 2, which will deliver VibratoSleeve prototypes that can then be used for verification testing in Aim 3. Acoustic verification in degassed waterbaths and human calf tissue phantoms will assess size and peak positive and negative pressures of the acoustic field generated by the VibratoSleeve. Measurement of power requirements will inform future design of the power source for the wearable VibratoSleeve, and transducer-phantom interface thermocouple measurements will assess the possibility of skin heating with long-term use. Vibrato has assembled a diverse group of technical, clinical and strategic advisors (as detailed in “Facilities and Other Resources”), including Key Opinion Leader Dr. Mahmood Razavi who, while not within the scope of this proposal, will perform Vibrato's Phase 1 clinical trials upon completion of this Phase 1 application.
Public Health Relevance Statement: Project Narrative Peripheral arterial disease (PAD) affects 202M people worldwide and 8.5M in the US, and is growing rapidly at a rate of 6.8%. Current PAD therapies have limited efficacy, and 250,000 patients per year in the US progress to critical limb ischemia (CLI), with resting pain, skin ulcers, gangrene, and often requiring amputation. Based upon recent studies demonstrating that therapeutic ultrasound (TUS) is effective in promoting collateral vessel growth and angiogenesis and improving perfusion, Vibrato Medical is developing a disruptive, paradigm-shifting PAD treatment with the first wearable device for non-invasive, outpatient use in order to improve symptoms and reduce amputations in PAD patients without other treatment options.
Project Terms: Acoustics; Address; Adoption; Affect; Ambulatory Care; Amplifiers; Amputation; Anatomy; angiogenesis; Animal Model; base; Catheters; claudication; Clinical; Clinical Data; clinical effect; clinical efficacy; Collaborations; Computer software; Coronary Arteriosclerosis; Data; demographics; design; Devices; effective therapy; experience; fibula; Frequencies; Future; Gangrene; Gastrocnemius Muscle; Generations; Goals; Growth; Hand; Health Personnel; Heating; Home environment; Hospitalization; Hour; Human; human data; improved; ineffective therapies; Intervention; Ischemia; Limb structure; Lower Extremity; Maintenance; Measurement; Measures; Medical; Methodology; Modality; Modeling; models and simulation; Needles; Obstruction; Operative Surgical Procedures; Outpatients; Output; Pain; Patients; Performance; Perfusion; Peripheral arterial disease; Phase; Phase I Clinical Trials; portability; Power Sources; pre-clinical; preclinical study; pressure; prevent; prototype; Reperfusion Therapy; Resources; Rest; restenosis; S Phase; Series; Skin; Skin Ulcer; Small Business Innovation Research Grant; Soleus Muscle; symptomatic improvement; Temperature; Testing; Therapeutic; therapy duration; tibia; Tibial Arteries; Time; tissue phantom; Tissues; Transducers; Ultrasonic Transducer; Ultrasonography; United States National Institutes of Health; voltage; wearable device; Weight; Work
