Clinical feasibility study of autonomous tibial nerve stimulator for overactive bladder

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.NARRATIVE Overactive bladder (OAB) profoundly impairs the ability to engage in social and occupational activities, and over 16 million Americans with OAB may benefit from a novel approach that is more patient-friendly, effective and safe than current solutions. This project will develop a self-powered implantable tibial nerve stimulator (ITNS) that provides symptom relief automatically without any action by the patient or caregiver, and will evaluate its safety and effectiveness in a small group of OAB patients. The findings will help guide the path to ITNS commercialization, and thus this proposal is directly responsive to the mission of the NIDDK to improve health and quality of life for OAB sufferers.