Clinical feasibility study of autonomous tibial nerve stimulator for overactive bladder

自主胫神经刺激器治疗膀胱过度活动症的临床可行性研究

• 批准号: 10064215
• 负责人: Peter Jacobson
• 金额: $ 74.59万
• 依托单位: NINE CONTINENTS MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-10 至 2021-01-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10064215
• 关键词: Adult; Adverse event; Affect; American; Caregivers; Cells; Charge; Clinic Visits; Clinical; Clinical Trials; Communication; Consumption; Data; Device Approval; Devices; Diagnostic; Distal; Effectiveness; Electrodes; Enrollment; Feasibility Studies; Feedback; Female; Frequencies; Gastrocnemius Muscle; Goals; Health; Human; Impairment; Implant; Incidence; Incontinence; Institutional Review Boards; Lead; Legal patent; Letters; Lithium; Longevity; Longitudinal Studies; Medial; Medical; Mental Depression; Mission; Monitor; Muscarinics; Muscle; National Institute of Diabetes and Digestive and Kidney Diseases; Nerve; Nocturia; Occupational; Output; Overactive Bladder; Paresthesia; Patient Self-Report; Patients; Pharmaceutical Preparations; Phase; Physiologic pulse; Positioning Attribute; Posterior Tibial Nerves; Power Sources; Pregnancy; Procedures; Quality of life; Reporting; Research; Risk; Safety; Secure; Severities; Shapes; Site; Stress Urinary Incontinence; Structure of tibial nerve; Surgical incisions; Symptoms; System; Techniques; Telemetry; Testing; Time; Woman; Work; base; commercial application; commercialization; compliance behavior; design; graphical user interface; implantation; improved; innovation; male; meetings; men; miniaturize; neuroregulation; novel strategies; operation; prospective; prototype; psychologic; reduce symptoms; responders and non-responders; response; side effect; social; subcutaneous; technological innovation; trial design; urinary; usability; user-friendly

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.

抽象的 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 等人） 等，2003）。 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 等，2014）。超过 1600 万患有 OAB 的美国人可能会失败或中止治疗 一线和二线治疗，但只有约 3% 的人接受三线治疗。因此，还有大量未开发的 创新三线疗法的市场。为了满足这一重大未满足的需求，项目总监，先生。 九大洲医疗公司的彼得雅各布森和他的同事开发了一种植入式胫骨 神经刺激器（ITNS）。这种受专利保护的小型自供电神经刺激器专为 通过一个 7 毫米切口的经皮手术将永久植入物植入小腿内侧。这 脉冲发生器位于皮下，短的集成电极引线将电脉冲传送到 胫后神经。 ITNS 通过遥测和 12 年名义寿命提供独特的诊断数据 无需任何外部设备进行充电或操作。在利用当前的几个方面的同时 经批准的三线疗法已证明有效，ITNS 可能具有更好的安全性 比当前的三线解决方案，其用户友好的功能旨在改善患者和护理人员 与外部供电概念相比的合规性。 为了推动 ITNS 商业化，该快速通道提案力求在第一阶段完善创新技术 编程系统，通过设计和测试（a）为程序员提供的集成神经刺激器，（b） 符合人体工程学的用户界面，以及 (c) 符合人体工程学的编程棒。完成这项工作后，我们的目标是 获得 FDA 和 IRB 批准启动临床可行性研究，并在 II 期完成。这个前瞻性的， 观察性、纵向单中心研究将招募 10 名患有 OAB 的受试者，他们在第一次和第二次试验中均未通过 一线治疗且至少符合 OAB 四个严重标准之一的人。他们不会有潜力 混杂病症，例如主要压力性尿失禁，其他风险，例如其他活动性尿失禁 植入物、具有泌尿系统副作用的并发药物（例如抗毒蕈碱药物）或计划或当前的药物 怀孕。 ITNS 植入后将对受试者进行 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 不需要假设检验。 ITNS 的首次人类使用结果将支持 IDE 应用程序 关键的临床试验并为该试验的设计提供信息。因此，本快速通道中的第一阶段和第二阶段活动 该提案是到 2023 年实现 ITNS 商业化的关键步骤。