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.

项目概要 拟议工作的目的是开发一个人类等级系统 通过控制胸神经的神经刺激来预防复发性晕厥 内脏静脉储库复发性晕厥，特别是神经介导性晕厥（NMS）， 仅在美国就影响了多达 300 万人的重大公共卫生问题。 由于跌倒或发生事故，晕厥会导致严重的发病和住院治疗 由于频繁的失败，这些频繁的身体并发症导致长期丧失能力。 在美国，因无法工作、无法驾驶和反复住院而造成的损失估计为 2 美元。 每年花费 10 亿美元用于晕厥患者的住院治疗。有效的治疗方法很少。 对于 NMS 患者。 Coridea 开发了一种通过动员血液治疗晕厥的新方法 通过刺激大动脉从内脏储存库到中央循环 我们已经开发了一个原型袖带和刺激系统。 并在大型动物身上进行了测试，证明了其可行性和安全性。 间歇性 GSN 刺激以及生理测量的所需变化 改善中心血流（下腔静脉血流量增加，中心静脉血流量增加） 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 减少再住院并改善患者发病率。 该直接进入第二阶段提案的目标集中于设备的优化 设计允许以微创方式放置神经刺激袖带和参数 安全有效的神经刺激，这将在动物研究中得到证明。 我们相信系统的设计将符合安全法规。 第二阶段 SBIR 结束时支持研究器械豁免 (IDE) 的证据 向联邦药物管理局（FDA）申请首次人体研究计划 阶段 IIb。 我们将与在以下领域拥有丰富经验的成熟合同制造集团合作： 电极套设计并将工程概念转化为临床。 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对人类的价值。 将进行研究以优化治疗参数、评估系统可用性和 证明在符合安全性研究中使用时不存在不良生物效应 良好实验室规范 (GLP) 的标准 在设备测试和 GLP 期间收集的数据。 动物研究将在下一阶段的工作中提交给FDA。