Prevention of Syncope with GSN Stimulation

通过 GSN 刺激预防晕厥

• 批准号: 9349575
• 负责人: Howard Levin
• 金额: $ 72.6万
• 依托单位: CORIDEA, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9349575
• 关键词: Accidents; Action Potentials; Acute; Adult; Adverse effects; Affect; Animal Model; Animals; Biological; Blood; Blood Circulation; Blood Pressure; Canis familiaris; Capital; Cardiac; Central venous pressure; Cerebrum; Chronic; Clinic; Clinical; Clinical Trials; Contracts; Data; Development; Device Designs; Device or Instrument Development; Devices; Electric Stimulation; Electrodes; Emergency department visit; Engineering; Evaluation; Family suidae; Functional disorder; Funding; Goals; Grant; Heart; Hospitalization; Human; Implant; Indwelling Catheter; Inferior vena cava structure; Investigation; Manufacturer Name; Measures; Mediating; Medical Device; Morbidity - disease rate; Nerve; Neural Pathways; Pathologist; Patients; Perfusion; Pharmaceutical Preparations; Phase; Physiological; Prevention; Procedures; Public Health; Recurrence; Reflex action; Regulation; Reproducibility; Research Infrastructure; Safety; Site; Small Business Innovation Research Grant; Splanchnic Circulation; Splanchnic Nerves; Structure of thoracic nerve; Syncope; System; Techniques; Testing; Therapeutic; Translations; Unconscious State; United States; Venous; Work; base; constriction; design; experience; falls; good laboratory practice; histopathological examination; implantation; improved; man; minimally invasive; neuroregulation; novel; novel strategies; novel therapeutics; pressure; programs; prototype; relating to nervous system; research and development; safety and feasibility; safety study; safety testing; structural heart disease; usability

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.

项目摘要 拟议工作的目的是开发人类级系统 通过神经刺激的胸神经系统来预防复发性晕厥 复发性晕厥，特别是中性介导的晕厥（NMS）， 仅在美国就影响了多达300万人的主要公共卫生问题。 晕厥会导致由于跌倒或事故引起的明显发病率和住院 由于经常失败。这些经常的身体并发症导致长期无法 上班，无法开车和复发住院。在美国，估计为2美元 每年将十亿个用于晕厥住院的患者。几乎没有治疗方法 适用于NMS的患者。 Coridea开发了一种通过动员血液来治疗晕厥的新方法 通过刺激更大的刺激 Schemechnic神经（GSN）。我们已经开发了原型袖口和刺激系统 并在大型动物中测试了它们。这项工作证明了 间歇性GSN刺激以及所需的物理测量变化 改善中心流量（下腔静脉的流动增加，中央静脉增加 压力，预加载量增加等）。因此，我们认为患者的GSN刺激 使用NMS可以安全地执行，并将导致预防晕厥，并最终导致 降低了重新占地并改善了患者的发病率。 该直接阶段II提案的目标集中在设备的优化上 设计以使神经刺激袖口的最小侵入性放置和参数 为了安全有效的神经刺激，将在动物研究中证明。 系统将旨在符合安全法规。我们相信会有足够的 在此II阶段SBIR结束时的证据以支持研究设备豁免（IDE） 向联邦药物管理局（FDA）申请计划的第一个人类研究 IIB期。 我们将与拥有经验的既定合同制造集团互动 电极袖口设计和工程概念向诊所的翻译。植入 神经刺激系统将根据合同制造商的设计控制进行设计 系统，最终使我们能够证明新型疗法在人类中的价值。动物 将进行研究以优化治疗参数，评估系统可用性和 在安全研究中，证明缺乏符合安全性的生物学作用 良好实验室实践标准（GLP）。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。