Prevention of Syncope with GSN Stimulation

项目摘要 拟议工作的目的是为联合国开发一个人类等级制度。 通过刺激控制晕厥的胸神经预防复发性晕厥 内脏静脉储集层。反复晕厥，特别是神经介导性晕厥(NMS)， 仅在美国就有多达300万人受到重大公共卫生问题的影响。 晕厥会导致严重的发病率和因跌倒或发生意外而住院治疗 由于屡屡失败。这些频繁的身体并发症会导致长期的不能 无法工作，不能开车，以及反复住院。在美国，大约2美元 每年花费在晕厥住院患者上的费用为10亿美元。几乎没有有效的治疗方法。 适用于NMS患者。 科里迪亚开发了一种通过动员血液来治疗晕厥的新方法 从内脏蓄水池到中心循环 内脏神经(GSN)。我们已经开发了一个袖带和刺激系统的原型 并在大型动物身上进行了测试。这项工作证明了该技术的可行性和安全性。 间歇性GSN刺激以及预期的生理测量变化 改善中心血流(下腔静脉血流增加，中心静脉增加 压力、增加的预加载等)。因此，我们认为刺激患者的GSN 使用NMS可以安全地进行，并将导致晕厥的预防，并最终 减少再次住院，改善患者发病率。 这一直接到第二阶段计划的目标集中在设备的优化 设计允许微创放置神经刺激袖带和参数 用于安全和有效的神经刺激，这将在动物研究中得到证明。这个 系统的设计将符合安全法规。我们相信，将有足够的 此第二阶段SBIR结束时支持调查设备豁免(IDE)的证据 向联邦药物管理局(FDA)提出申请，进行计划于 第二阶段。 我们将与具有以下经验的老牌合同制造集团接洽 电极套的设计和工程概念的临床应用。植入物 神经刺激系统将在合同制造商的设计控制下进行设计 系统，最终使我们能够证明这种新疗法在人类身上的价值。动物 将进行研究，以优化处理参数，评估系统可用性和 证明在符合以下要求的安全性研究中使用时没有不良生物影响 良好实验室操作规范标准(GLP)。在设备测试和GLP期间收集的数据 动物研究将在下一阶段提交给FDA。

Project Summary The purpose of the proposed work is the development of a human-grade system for the prevention of recurrent syncope through neurostimulation of the thoracic nerves controlling the splanchnic venous reservoir. Recurrent syncope, specifically neurally mediated syncope (NMS), is major public health problem affecting as many as 3 million people in the United States alone. Syncope results in significant morbidity and hospitalization due to falls or accidents that occur as a result of frequent failing. These frequent physical complications result in prolonged inability to work, inability to drive, and recurrent hospitalizations. In the United States an estimated $2 billion is spent annually on patient hospitalized for syncope. There are few treatments that work for patients with NMS. Coridea has developed a novel approach for treating syncope by the mobilization of blood from the splanchnic reservoir to the central circulation by means of stimulation of the greater splanchnic nerve (GSN). We have already developed a prototype cuff and stimulation system and tested them in large animals. This work demonstrated the feasibility and safety of intermittent GSN stimulation as well as the desired changes in physiological measures of improved central flow (increased flow in the inferior vena cava, increased central venous pressure, increased preload, etc.). We therefore believe that stimulation of the GSN in patients with NMS can be carried out safely and will lead to prevention of syncope and ultimately reduced re-hospitalization and improved patient morbidity. The goals of this Direct-to-Phase II proposal are focused on the optimization of device design to allow for minimally invasive placement of the neurostimulation cuff and the parameters for safe and effective neurostimulation, which will be demonstrated in animal studies. The system will be designed to conform to safety regulations. We believe that there will be sufficient evidence at the end of this Phase II SBIR to support an investigational device exemption (IDE) application to the Federal Drug Administration (FDA) for the first-in-human studies planned for Phase IIb. We will engage with established contract manufacturing groups with experience in electrode cuff design and translation of engineering concepts to the clinic. The implantable neurostimulation system will be engineered under the contract manufacturers’ design control system, ultimately enabling us to prove the value of the novel therapy in humans. Animal studies will be performed to optimize the treatment parameters, evaluate system usability and demonstrate absence of untoward biological effects using in a safety study conforming to the standards of good laboratory practices (GLP). Data collected during device testing and GLP animal studies will be submitted to the FDA in the next phase of the work.