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

项目总结 外周动脉疾病(PAD)是一种高度流行的疾病，由于移位而迅速增长。 全球有2.02亿人受到影响，美国有1800万人，年增长率为6.8%。 PAD对老年人的影响不成比例。在老年人中观察到的PAD患病率最高 成年人：在80岁的人中≥为22.7%，在40-49岁的人中为1.6%。早期阶段 PAD的晚期会导致跛行，而PAD的晚期会导致静息痛、皮肤溃疡、坏疽 和截肢，所有这些都降低了老年人的行动能力、功能和独立性。导管技术的进展-- 基础治疗包括血管成形术、支架植入和药物涂层球囊，以及外科搭桥 治疗，在PAD中往往无效，并伴随着并发症和高达40%的长期发生率 血管再狭窄。 治疗超声(TUS)等声能疗法已被证明可以促进侧支循环。 在冠状动脉疾病和PAD动物模型中，为了改善血管生长、血管生成和改善血流灌注， 在这两种疾病过程中都有很有希望的早期人类数据。 Vibrato Medical开发了一种新的治疗方法，它使用了第一个可穿戴的治疗性超声波(TUS)设备 对于PAD的非侵入性门诊治疗，将促进侧支血管生长和血管生成， 恢复血流，降低截肢率。我们已经展示了VibratoSleve的功效 采用多种灌流措施显著改善健康志愿者的下肢血流灌注。 此Fast Track SBIR提案的目标是进行以下前瞻性开放标签临床试验(第一阶段 通过随机假对照研究(II期)，旨在评估血流灌注的改善和 65岁以上PAD患者的功能结局。共有12名受试者将获得可穿戴设备 在3次不同的诊所就诊中，对小腿后部进行90分钟的急性振动睡眠治疗，36名患者将 在45天内接受30次慢性治疗，每次90分钟，并将对 另在治疗后45天。疗效将通过比较基线和治疗中的高峰步行进行评估。 标准分级跑台试验时间(主要终点)、下肢远端灌注率和组织 氧合和血红蛋白以及踝关节和脚趾臂部指数。我们还将系统地获得 患者使用标准化问卷对VibratSleve的易用性、耐受性和舒适性进行反馈。 关于触觉和舒适性的数据将为最佳声学参数和下一代 可控震荡产品。随着我们所有的测试和临床研究完成，Vibrato将申请美国FDA 510(K) 产品的清关。

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.