Clinical study of a wearable therapeutic ultrasound sleeve for treatment of neuro-ischemic and ischemic diabetic foot ulcers

项目摘要 糖尿病（DM）是一种常见疾病（在美国为34 M）。大约七分之一的糖尿病患者患有糖尿病 足部溃疡（DFU）。大约一半的DFU患者伴有外周动脉疾病（PAD）， 导致250万例缺血性或神经缺血性DFU患者在美国患病。DFU患者 经历反复住院，慢性伤口愈合问题，并最终截肢， 限制生活质量和生产力，给家庭带来沉重的护理负担， 医疗保健系统。DFU患者经历了一些骨切除（750 K至1.35 M）或 截肢（17万），使新的选择，以治疗这些患者，并防止昂贵的 截肢和住院治疗。患有DFU的患者也患有PAD， 由于输送血液到小腿的大动脉和小动脉中的血液流动都很差， 分支出来供应小腿和脚的肌肉和组织的血管。 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。 该I期SBIR提案的目标是进行一项前瞻性开放标签临床试验，旨在评估 缺血性或神经缺血性DFU灌注的急性改善。共有12名受试者将接受 在3次单独的门诊访视时，对小腿后部进行90分钟的可穿戴VibratoSleeve治疗， 中等和高声强设置。将通过比较基线和治疗期间来评估疗效。 治疗，并将在所有3种强度下比较每个终点的平均改善， 剂量反应关系我们还将系统地获得患者对易用性、耐受性、 使用每90分钟后进行的标准化问卷调查， 治疗关于触觉和舒适度的数据将为最佳声学参数、治疗 评估DFU的长期TUS治疗的后续假对照临床试验的持续时间和设计 治愈

PROJECT SUMMARY Diabetes mellitus (DM) is a common condition (34M in USA). Approximately 1 in 7 DM patients have diabetic foot ulcers (DFU). Approximately half of patients with DFU have concomitant peripheral arterial disease (PAD), resulting in US prevalence of 2.5M patients with ischemic or neuroischemic DFUs. Patients with DFUs experience recurrent hospitalizations, chronic wound healing issues, and ultimately amputations that severely limit quality of life and productivity and place a significant burden of care on families and a sizable cost for the healthcare system. The patients with DFUs experience either some bone removal (750K to 1.35M ) or amputation (170K) annually, making new options necessary to treat these patients and prevent the costly amputations and hospitalizations. Patients with DFU’s who also have PAD experience these symptoms because of poor blood flow both in the larger arteries delivering blood to the lower leg and in the smaller vessels branching out to supply the muscles and tissues of the lower leg and foot. 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 Phase I SBIR proposal is to conduct a prospective open-label clinical trial designed to evaluate the acute improvement in perfusion to ischemic or neuro-ischemic DFUs. A total of 12 subjects will receive wearable VibratoSleeve treatment to the posterior calf for 90 minutes at 3 separate clinic visits at low, medium and high acoustic intensity settings. Efficacy will be assessed by comparing baseline and on- therapy, and mean improvements in each endpoint will be compared across all 3 intensities to determine a dose-response relationship. We will also systematically obtain patient feedback on ease of use, tolerability, and comfort of VibratoSleeve using a standardized questionnaire administered after each 90-minute treatment. Data on the tactile sensation and comfort will inform optimal acoustic parameters, treatment duration and design of a subsequent sham-controlled clinical trial of long-term TUS therapy to assess DFU healing.