Clinical feasibility study of autonomous tibial nerve stimulator for overactive bladder

摘要 膀胱过度活动症（OAB）影响大约16%的美国成年人，男性和女性都一样（Stewart，et 例如，2003年）。OAB可以深刻影响生活质量，甚至可以产生心理影响，包括 抑郁症（Gormley，et al.，2014）。超过1600万患有OAB的美国人可能会失败或中断 一线和二线治疗，但只有约3%的人追求三线治疗。因此，有一个巨大的未开发的 创新的三线疗法的市场。为应对这一重大未满足的需求，项目主任，先生。 九大洲医疗公司的彼得·雅各布森和他的同事们。已经开发出一种可植入的胫骨 神经刺激器（ITNS）。这种受专利保护的小型化自供电神经刺激器设计用于 小腿内侧下部的永久性植入物，通过单7 mm切口的经皮手术。的 脉冲发生器是皮下的，短的集成电极导线将电脉冲输送到 胫后神经ITNS独特地通过遥测技术提供诊断数据，标称寿命为12年 而不需要任何用于充电或操作的外部设备。同时利用目前的几个方面- 经批准的三线治疗已证明有效，ITNS可能具有更好的安全性 比当前的三线解决方案更好，其用户友好的功能旨在改善患者和护理人员的状况 与外部供电概念相比， 为了推进ITNS商业化，这一快速通道建议在第一阶段寻求完善创新的 通过设计和测试（a）程控仪的集成神经刺激器，（B） 人体工程学用户界面，和（c）人体工程学编程棒。随着这项工作的完成，我们的目标是 获得FDA和IRB的批准，以启动将在II期完成的临床可行性研究。这种前瞻性的、 一项观察性、纵向单中心研究将入组10例首次和第二次治疗失败的OAB受试者， 线治疗，并且符合OAB的四个严重程度标准中的至少一个。他们不会有潜在的 混杂疾病，如主要压力性尿失禁，其他风险，如其他活性 植入物、伴随药物（如抗毒蕈碱药）或计划或当前使用的泌尿系统副作用 怀孕受试者将在ITNS植入后监测26周，以收集客观安全性和 有效性数据以及自我报告的生活质量。FDA已经审查了这项可行性研究， 不需要假设检验。ITNS的首次人类使用的结果将支持IDE应用程序， 一个关键的临床试验，并告知该试验的设计。因此，这一快速通道的第一和第二阶段活动 该提案是到2023年将ITNS商业化的关键步骤。

ABSTRACT Overactive bladder (OAB) affects approximately 16 percent of U.S. adults, men and women alike (Stewart, et al., 2003). OAB can profoundly impact quality of life and can even have psychological repercussions including depression (Gormley, et al., 2014). More than 16 million Americans with OAB are likely to fail or discontinue first- and second-line therapy, but only about 3% pursue third-line therapy. Thus, there is a large untapped market for an innovative third-line therapy. In response to this significant unmet need, the Project Director, Mr. Peter Jacobson, and his colleagues at Nine Continents Medical, Inc. have developed an implantable tibial nerve stimulator (ITNS). This patent-protected, miniaturized, self-powered neurostimulator is designed for permanent implant in the medial lower calf, via a percutaneous procedure with a single 7-mm incision. The pulse generator is subcutaneous, and a short integrated electrode-lead delivers electrical pulses to the posterior tibial nerve. ITNS uniquely provides diagnostic data via telemetry and 12-year nominal longevity without requiring any external device for charging or operation. While leveraging several aspects of currently- approved third-line therapies that have demonstrated effectiveness, ITNS is likely to have a better safety profile than current third-line solutions, and its user-friendly features are designed to improve patient and caregiver compliance compared to externally-powered concepts. To advance the ITNS to commercialization, this Fast-Track proposal seeks, in Phase I, to refine the innovative programming system by designing and testing (a) an integrated neurostimulator for the programmer, (b) an ergonomic user interface, and (c) an ergonomic programming wand. With this work completed, we aim to obtain FDA and IRB approval to initiate a clinical feasibility study to be completed in Phase II. This prospective, observational, longitudinal single-site study will enroll 10 subjects with OAB who have failed first- and second- line therapy and who meet at least one of four severity criteria for OAB. They will not have potentially confounding conditions such as predominant stress incontinence, additional risks such as other active implants, concurrent medications with urinary side effects such as anti-muscarinics, or planned or current pregnancy. Subjects will be monitored for 26 weeks following ITNS implantation to collect objective safety and effectiveness data as well as self-reported quality of life. The FDA has reviewed this feasibility study and does not require hypothesis testing. Results from this first human use of the ITNS will support an IDE application for a pivotal clinical trial and inform the design of that trial. Thus, Phase I and II activities in this Fast-Track proposal are key steps for positioning the ITNS for commercialization by 2023.