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

摘要 在老龄化人口中，膀胱过度活动是一种慢性和破坏性的疾病。大约3300万 美国人患有膀胱过度活动症(OAB)和相关的尿急失禁(UUI)， 一种慢性疾病，严重损害生活质量，并导致每年 660亿美元。这种慢性排尿障碍的心理方面尤其具有破坏性；患者 增加了抑郁、社会孤立和睡眠剥夺的发生率。鉴于OAB的发病率 随着年龄的增长，该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，这一比例也在上升。尽管社会和经济负担沉重，但方便、安全和 有效的治疗方法尚未实现。最近，一种微创神经调节设备提供了 经皮胫神经刺激(PTNS)传入骶神经，Congentix的URGRENT®PC已显示 临床成功；然而，这种装置需要每周的临床治疗以及重复放置一个 将电极插入胫后神经，这两种方法的成本都很高，而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，最初的临床研究有很高的并发症发生率， 经常需要二次手术来解决这些不良事件。以满足对安全、有效、 对于OAB，TheraNova开发了一种廉价、方便的治疗方法 这使得在家里进行非侵入性的胫神经刺激成为可能。之前，我们证明了受试者接受了 通过该系统实现了平均空隙数的减少，具有中等到 严重的紧迫性，以及UUI事件的平均数量。此第二阶段提案的目标是确定 在一项家庭使用的关键临床研究中，我们的系统与假对照治疗的有效性。首先，我们将 进行一项临床研究，以确定良好的盲法假对照治疗(特定目标1)。第二，我们将验证 与假手术对照组比较缓解急迫性尿失禁的疗效和耐受性 在一个关键的试验中(特定目标2)。获得的数据将支持FDA 510(K)的批准，并将使我们能够 在这项提案获得资金后的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.