Clinical Trial and Commercialization of a Wearable Therapeutic Ultrasound Device for Peripheral Arterial Disease

Project SummaryPeripheral arterial disease (PAD) is a highly prevalent condition that is growing rapidly due to shifting demographics, affecting 202M people worldwide and 18M 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, with 30% of patients requiring amputation and a mortality rate of 25% within 1 year post diagnosis. 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 both disease processes. Vibrato Medical has developed 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 landscape with a non-invasive, wearable, outpatient treatment (1-8 hours during rest or sleep) that will prevent amputations, hospitalizations and other complications of advanced PAD. We have already demonstrated VibratoSleeveandapos;s efficacy in markedly improving lower extremity perfusion in healthy volunteers using multiple perfusion measures.The goal of this NIH Phase II SBIR proposal is to perform a pilot randomized, sham-controlled clinical trial of the VibratoSleeve in 24 PAD patients with CLI, then build a 2nd generation device with which to obtain 510(k) clearance. In Aim 1, Vibrato will build a 16-channel generator with integrated patient interface unit that will power the wearable VibratoSleeve array that was designed and built in Phase 1. Six total systems will be built, and undergo verification and validation for clinical trial readiness. In Aim 2, Vibrato will conduct a double- blinded, randomized, sham-controlled clinical trial of 24 patients (Rutherford Class 3-5 with infra-popliteal PAD and no revascularization options) with Dr. Mahmood Razavi at Vascular and Interventional Specialists of Orange County. In Aim 3, Based on the efficacy, safety and patient feedback data from Aim 2, Vibrato will then develop its 2nd generation commercial VibratoSleeve and its entirely portable generator, such that the entire device will be wearable.With all our testing and clinical study done, Vibrato will apply for US FDA 510(k) clearance of the product as well as CE approval for European distribution.Project NarrativePeripheral arterial disease (PAD) affects 202M people worldwide and 18M in the US, and is growing rapidly at a rate of 6.8%. Current PAD therapies have limited efficacy, and 250K patients per year in the US progress to critical limb ischemia (CLI), with resting pain, skin ulcers, gangrene, often requiring amputation or resulting in death. Based upon recent studies demonstrating that therapeutic ultrasound (TUS) is effective in promoting collateral vessel growth and angiogenesis and improving perfusion, Vibrato Medical has developed a disruptive, paradigm-shifting PAD treatment with the first wearable device for non- invasive, outpatient use (for 1-8 hours during rest or sleep) in order to improve symptoms and reduce amputations in PAD patients without other treatment options.