Clinical readiness of Uzap - the minimally invasive Overactive Bladder treatment

摘要 膀胱过度活动(OAB)严重影响了美国超过12%的成年人口 -大约3000万人(欧文等人，2006年)。急促和频繁的排尿冲动、性唤醒 睡眠，有时还有大小便失禁，会造成巨大的社会心理和经济成本， 仅在美国每年造成的经济负担估计就达700亿美元(Reynolds等人， 2016)。目前的OAB干预措施多种多样，包括药物、神经刺激剂、 肉毒杆菌毒素注射和外科手术，所有这些都有不良副作用和 缺乏广泛和持久的效力。此外，药物治疗需要长期服药和 其他治疗方法可能需要重复的临床干预。 Stellartech研究公司正在开发用于经尿路的NewUro UZAP设备 射频黏膜隔断术。它是唯一一种微创，单疗程，非药物， 在不影响排尿功能的情况下缓解OAB症状的非植入疗法。 研究表明，在膀胱癌模型中，膀胱粘膜内存在过度的电连接 过度活动(Kanai等人，2007年)。这导致了波状本征的夸大传播 电和机械活动，预计可接受治疗的最低限度 UZAP对黏膜隔离线的侵入性热消融。尤扎普背后的创新 该系统已经被7项授权专利覆盖。UZAP消融整体的初步研究 猪膀胱和组织标本对激动剂的收缩反应减弱。 成功的临床前安全性和性能测试在体外完成，并在 活体猪模型。此快速通道提案在第一阶段寻求展示长期的 尤扎普疗法的活体安全性和持久性，在第二阶段，到1)进行长期动物实验 安全性和有效性研究；2)优化系统和电极设计及可用性和制造 验证和确认单元；3)执行验证和确认测试；举行预集成开发 (研究设备豁免)会议并提交未来第一个IDE申请- 30例女性难治性尿失禁多动膀胱患者的人体试验。这个 拟议的严谨工作将为将UZAP推进到临床阶段和 走向商业化，以便为数百万患者提供缓解并消除 用于植入物或重复的临床干预。

Abstract Overactive bladder (OAB) severely impacts over 12% of the adult population in the United States – roughly 30 million people (Irwin, et al., 2006). Pressing and frequent urges to urinate, arousal from sleep, and sometimes incontinence, result in immense psychosocial and financial costs, leading to an estimated annual economic burden of >$70B in the US alone (Reynolds, et al., 2016). Current OAB interventions are varied and include pharmaceuticals, neurostimulators, botulinum toxin injections, and surgical approaches, all of which have adverse side effects and lack widespread and enduring efficacy. In addition, drug therapies require long-term dosing and other treatments can require repeat clinical interventions. Stellartech Research Corporation is developing the NewUro Uzap device for transurethral radiofrequency mucosal partitioning. It is the only minimally-invasive, single-session, non-drug, non-implant therapy for alleviating the symptoms of OAB without compromising voiding function. Research has shown excessive electrical connectivity within the bladder mucosa in models of overactivity (Kanai et al., 2007). This results in exaggerated propagation of wave-like intrinsic electrical and mechanical activity, which is anticipated to be amenable to therapy by minimally invasive thermal ablation of mucosal isolation lines by the Uzap. The innovations behind the Uzap system are already covered by 7 granted patents. Preliminary studies of Uzap ablation on whole pig bladder and tissue specimens demonstrated reduced contractile response to agonists. Successful preclinical safety and performance tests were completed in ex vivo and preliminary in vivo porcine models. This Fast-Track proposal seeks, in Phase 1, to demonstrate long-term in vivo safety and durability of Uzap therapy, and, in Phase 2, to 1) perform a long-term animal safety and efficacy study; 2) optimize system and electrode design and usability and fabricate Verification and Validation units; 3) perform Verification and Validation tests; hold a pre-IDE (Investigational Device Exemption) meeting and submit an IDE application for a future First-In- Human trial of 30 female patients with refractory overactive bladder with incontinence. The rigorous work proposed will create a firm base for advancing the Uzap to the clinical phase and towards commercialization, in order to provide relief for millions of patients and eliminate the need for implants or repetitive clinical interventions.