A Non-Invasive Neuromodulation Device for In-Home Treatment of Overactive Bladder

摘要 膀胱过度活动症是一种慢性和破坏性的条件在老龄化人口。约3300万 美国人患有膀胱过度活动症（OAB）和相关的急迫性尿失禁（UUI）， 一种严重损害生活质量并导致每年经济负担的慢性疾病， 660亿美元这种慢性排尿功能障碍的心理方面尤其具有破坏性; 抑郁症、社交孤立和睡眠不足的发病率增加。考虑到OAB的发生率 随着年龄的增长，这种疾病的患病率和总的经济负担将继续增加， 随着婴儿潮一代人口的老龄化而上升。尽管有很高的社会和经济负担， 有效治疗尚待实现。最近，一种微创神经调节装置， 骶神经传入神经的经皮胫神经刺激（PTNS），Congentix的Urgent® PC，已显示 临床成功;然而，该器械需要每周一次的门诊治疗以及重复放置 将电极插入胫后神经，这两者都是成本高昂的，并且对患者的依从性具有挑战性。 植入式神经刺激器（RENOVA iStim和eCoin™）也在开发中，但这些设备 需要外科手术，因此，最初的临床研究具有高并发症发生率， 通常需要二次手术来解决这些不良事件。为了满足安全、有效、 舒适，易于使用的治疗OAB，TheraNova开发了一种便宜，方便的设备 能够在家中进行无创胫神经刺激。之前，我们证明了接受治疗的受试者 利用该系统实现了平均空隙数的减少，具有中等至 严重紧迫性和UUI事件的平均数量。第二阶段提案的目标是确定 在一项家用关键临床研究中，我们的系统与假对照治疗的有效性。一是 进行临床研究，以确定一种良好的设盲假手术对照治疗（具体目标1）。第二，我们将验证 与假手术对照组相比，缓解急迫性尿失禁的治疗有效性和持久性 在一项关键试验中（具体目标2）。获得的数据将支持FDA 510（k）许可，并使我们能够 在本提案获得资金后的3.5年内将该系统商业化。

Abstract Overactive bladder is a chronic and devastating condition in the aging population. Approximately 33 million people in the United States suffer from overactive bladder (OAB) and associated urinary urge incontinence (UUI), a chronic medical condition that drastically impairs quality of life and results in an annual economic burden of $66 billion. The psychological aspects of this chronic voiding dysfunction are particularly devastating; patients have increased incidences of depression, social isolation and sleep deprivation. Given that the incidence of OAB increases with advancing age, the prevalence of the condition and the total economic burden will continue to rise as the baby boomer population ages. Despite the high social and economic burden, a convenient, safe and effective treatment has yet to be realized. Recently, a minimally invasive neuromodulation device that provides percutaneous tibial nerve stimulation (PTNS) of the afferent sacral nerve, Congentix’s Urgent® PC, has shown clinical success; however, this device requires weekly in-clinic treatments as well as repeated placement of an electrode into the posterior tibial nerve, both of which are cost prohibitive and challenging for patient adherence. Implantable neurostimulators (RENOVA iStim and eCoin™) are also under development, but these devices require a surgical procedure and, accordingly, initial clinical studies have had high complication rates, with a second surgery often required to address these adverse events. To meet the need for a safe, effective, comfortable, and easy-to-use treatment for OAB, TheraNova has developed an inexpensive, convenient device that enables non-invasive tibial nerve stimulation at home. Previously, we demonstrated that subjects treated with this system achieved reductions in the mean number of voids, the mean number of voids with moderate to severe urgency, and the mean number of UUI events. The goals of this Phase II proposal are to determine the effectiveness of our system versus a sham control treatment in a home-use, pivotal clinical study. First, we will conduct a clinical study to identify a well-blinded sham control treatment (Specific Aim 1). Second, we will validate the treatment effectiveness and durability for mitigating urinary urge incontinence compared to the sham control in a pivotal trial (Specific Aim 2). The data obtained will support FDA 510(k) clearance and will allow us to commercialize the system within 3.5 years of the funding of this proposal.