Clinical feasibility study of autonomous tibial nerve stimulator for overactive bladder

摘要 膀胱过度活动症(OAB)影响着大约16%的美国成年人，无论男性还是女性(Stewart，et 等人，2003年)。OAB可以深刻地影响生活质量，甚至会产生心理影响，包括 抑郁症(Gormley等人，2014)。超过1600万患有OAB的美国人可能会失败或停止治疗 一线和二线治疗，但只有约3%的人追求三线治疗。因此，有大量未开发的 一种创新的三线疗法的市场。为了满足这一重大的未得到满足的需求，项目主任李先生。 彼得·雅各布森和他在九洲医疗公司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专为 永久植入小腿内侧，通过一个7毫米的切口经皮操作。这个 脉冲发生器是皮下的，一个短的集成电极导线将电脉冲传送到 胫后神经。ITNS通过遥测和12年标称寿命提供独特的诊断数据 不需要任何外部设备进行充电或操作。同时利用当前- 已经证明有效的已获批准的三线疗法，ITNS可能会有更好的安全性 与当前的三线解决方案相比，其用户友好的功能旨在改善患者和护理人员 合规性与外部动力概念相比。 为了将ITN推向商业化，这项快速通道提案寻求在第一阶段完善创新的 通过设计和测试(A)用于程序员的集成神经刺激器，(B)和 人体工程学用户界面，以及(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，以启动将在第二阶段完成的临床可行性研究。 观察性的、纵向的单部位研究将招募10名OAB患者，他们第一次和第二次失败。 行疗法，且至少符合OAB的四个严重标准之一。他们不会有潜在的 混合性情况，如压力性大小便失禁，其他风险，如其他活跃 植入物，合并有尿路副作用的药物，如抗毒鼠药，或计划或当前 怀孕了。植入ITN后，受试者将接受为期26周的监测，以收集客观的安全性和 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，并做了 不需要假设检验。第一次人类使用ITN的结果将支持IDE应用程序 一个关键的临床试验，并为该试验的设计提供信息。因此，该快车道中的第一阶段和第二阶段活动 提案是到2023年将ITN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.