Non-invasive therapeutic ultrasound device for treatment of peripheral arterial disease in elderly population

项目摘要 外周动脉疾病（PAD）是一种高度流行的疾病，由于转变而迅速增长 人口统计数据，影响全球2.02亿人，美国1800万人，年增长率为6.8%。 PAD对老年人的影响很大。在老年人中观察到PAD的发病率最高 成人：≥80岁的个体中为22.7%，40-49岁的个体中为1.6%。早期阶段 PAD的晚期可导致跛行，而PAD的晚期可导致静息痛、皮肤溃疡、坏疽 和截肢，所有这些都降低了老年人的流动性，功能和独立性。导管的进展- 包括血管成形术、支架植入术、药物涂层球囊以及外科搭桥术 治疗通常对PAD无效，并伴有并发症，长期并发症率高达40% 再狭窄 声学能量模态，如治疗性超声（TUS），已被证明可以促进侧支循环 血管生长、血管生成，并改善冠状动脉疾病和PAD动物模型的灌注， 在这两种疾病的早期人类数据中， Vibrato Medical开发了一种新型治疗方法，采用第一种可穿戴治疗超声（TUS）设备 对于PAD的非侵入性门诊治疗，其将促进侧支血管生长和血管生成， 恢复灌注并降低截肢率。我们已经证明了VibratoSleeve的功效， 使用多种灌注测量显著改善健康志愿者的下肢灌注。 本快速通道SBIR提案的目标是进行前瞻性开放标签临床试验（I期）， 通过随机化假对照研究（II期），旨在评价灌注和 65岁以上PAD患者的功能结局。共有12名受试者将接受可穿戴设备 VibratoSleeve在3次单独的诊所访视中对小腿后部进行了90分钟的急性治疗，36名患者将 在45天内接受30次慢性治疗，每次90分钟，并将进行随访 治疗后45天。将通过比较基线和治疗期间峰值步行来评估疗效 标准分级跑台试验时间（主要终点）、远端下肢灌注率和组织 氧合和血红蛋白以及踝肱指数和趾肱指数。我们还将系统地获取 使用标准化问卷调查患者对VibratoSleeve的易用性、耐受性和舒适度的反馈。 触觉和舒适性数据将为最佳声学参数和下一代提供信息 VibratoSleeve产品。随着我们所有的测试和临床研究的完成，Vibrato将申请美国FDA 510（k） 清除产品。

PROJECT SUMMARY Peripheral 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%. PAD disproportionally affects the elderly. The highest prevalence of PAD has been observed among older adults: 22.7% among individuals ≥80 years of age versus 1.6% among those 40–49 years of age. Early stages of PAD result in claudication, while the advanced stage of PAD results in resting pain, skin ulcers, gangrene and amputation, all of which reduce mobility, function and independence of seniors. Advances in catheter- based therapies including angioplasty, stenting, and drug-coated balloons, as well as surgical bypass treatments, are often ineffective in PAD and associated with complications and up to 40% rate of long-term restenosis. Acoustic energy modalities such as therapeutic ultrasound (TUS) have been shown to promote collateral vessel growth, angiogenesis, and to improve perfusion in animal models of coronary artery disease and PAD, with promising early human data in both disease processes. Vibrato Medical has developed a novel treatment with the first wearable therapeutic ultrasound (TUS) device for the non-invasive, outpatient treatment of PAD that will promote collateral vessel growth and angiogenesis, restore perfusion and reduce amputation rates. We have already demonstrated VibratoSleeve’s efficacy in markedly improving lower extremity perfusion in healthy volunteers using multiple perfusion measures. The goal of this Fast Track SBIR proposal is to conduct a prospective open-label clinical trial (Phase I) followed by randomized sham-controlled study (Phase II) designed to evaluate the improvement in perfusion and functional outcomes of PAD patients over 65 years of age. A total of 12 subjects will receive wearable VibratoSleeve acute treatment to the posterior calf for 90 minutes at 3 separate clinic visits and 36 patients will receive chronic treatment for 30 sessions of 90 minutes each over 45-day period and will be followed up for another 45 days post-treatment. Efficacy will be assessed by comparing baseline and on-therapy peak walking time on a standard graded treadmill test (primary endpoint), distal lower extremity perfusion rate and tissue oxygenation and hemoglobin as well as ankle- and toe-brachial indices. We will also systematically obtain patient feedback on ease of use, tolerability, and comfort of VibratoSleeve using a standardized questionnaire. Data on the tactile sensation and comfort will inform optimal acoustic parameters and the next generation VibratoSleeve product. With all our testing and clinical study done, Vibrato will apply for US FDA 510(k) clearance of the product.