Wireless Nerve Stimulation Device To Enhance Recovery After Stroke

无线神经刺激装置可促进中风后恢复

• 批准号: 10434962
• 负责人: SETH ALANSON HAYS
• 金额: $ 115.65万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10434962
• 关键词: Affect; Animals; Caring; Cerebral hemisphere hemorrhage; Chemicals; Chronic; Clinical; Clinical Research; Clinical Trials; Communication; Computer software; Consumption; Cross-Over Studies; Data; Development; Device Designs; Devices; Documentation; Double-Blind Method; Encapsulated; Environmental Monitoring; FDA approved; Family; Glass; Gold; Guidelines; Hand functions; Harvest; Human; Human Resources; Implant; In Vitro; Individual; Injury; Institutional Review Boards; Intervention; Ischemic Stroke; Lead; Life; Magnetic Resonance Imaging; Mechanics; Medical; Nerve; Nervous System Trauma; Neurological Models; Operative Surgical Procedures; Patients; Phase; Physical Rehabilitation; Placebo Control; Process; Production; Randomized; Recording of previous events; Recovery; Recovery of Function; Rehabilitation device; Rehabilitation therapy; Risk; Running; Second Look Surgery; Sensory; Series; Societies; Spinal cord injury; Sterility; Stroke; System; Techniques; Technology; Testing; Time; Training; Translating; Translations; Traumatic Brain Injury; United States; Upper Extremity; Vagus nerve structure; Work; base; biomaterial compatibility; chronic stroke; clinically significant; cost; cost effective; design; disability; first-in-human; implantable device; improved; in vivo; innovation; manufacturing process; meetings; motor recovery; nervous system disorder; neuroregulation; novel; post stroke; pre-clinical; research clinical testing; safety and feasibility; sterility testing; stroke intervention; stroke patient; stroke rehabilitation; stroke therapy; success; vagus nerve stimulation; verification and validation; wireless; wrist function

ABSTRACT Stroke is highly prevalent, debilitating, and lacks consistently effective post-injury interventions. We have developed an innovative technique using vagus nerve stimulation (VNS) delivered during rehabilitation to engage plasticity-enhancing neuromodulatory circuits and improve recovery of motor and sensory function after stroke. Our preclinical findings demonstrate that VNS paired with rehabilitative training enhances recovery in multiple models of neurological injury, including ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and spinal cord injury. Moreover, our two recent clinical studies in chronic stroke patients indicate that VNS is safe and yields a significant three-fold increase in recovery of upper limb function compared to rehabilitation without VNS. While the scientific and clinical evidence is encouraging, the VNS device used to perform these studies is substantially limited by an inflexible stimulation paradigm, lead fragility, limited battery life, large size, and high cost. These technical limitations preclude effective translation of this potentially transformative therapy. We have developed a novel low-cost, clinical-grade VNS system that obviates these deficiencies. The system consists of a miniature wireless, lead-less, passive implantable stimulator that is placed on the vagus nerve and an external power and communications module that controls the implantable stimulator. The implantable device is manufactured at the wafer level using an automated process with materials that are FDA-approved for human use and MRI-compatible, thus providing reliability and lowering cost 25-fold compared to commercially-available devices. The implantable stimulator is hermetically encapsulated in biocompatible glass and is 50 times smaller than existing VNS devices, reducing the invasiveness of the implant surgery. Moreover, the implanted device is passive and harvests power from the external module, eliminating the need for a bulky implanted battery and surgical revision for battery replacement. Much of the required testing is complete, but final verification and validation is necessary to allow IDE submission and clinical evaluation. In this proposal, we outline a series of critical steps to translate this robust, cost-effective device to provide tangible improvements in the lives of stroke patients. In the UG3 phase, we will finalize verification and validation of the embedded software and create a design history file. Additionally, we will confirm biocompatibility in a chronic large animal study and finalize package sterility testing. Once complete, we will gain approval for an IDE. In the UH3 phase, we will perform a double-blind, randomized, placebo-controlled crossover study to evaluate the VNS therapy system in chronic stroke patients. Successful completion of this project will move this device from the verge of translation into human trials with a direct focus on a subsequent pivotal trial.

抽象的 中风非常普遍，使人衰弱，并且缺乏持续有效的伤后干预措施。我们有 开发了一种创新技术，利用康复期间提供的迷走神经刺激（VNS）来参与 增强神经调节回路的可塑性并改善中风后运动和感觉功能的恢复。 我们的临床前研究结果表明，VNS 与康复训练相结合可增强多种疾病的恢复 神经损伤模型，包括缺血性中风、脑出血、创伤性脑损伤和 脊髓损伤。此外，我们最近对慢性中风患者进行的两项临床研究表明 VNS 是安全的 与没有康复的康复相比，上肢功能的恢复显着增加三倍 迷走神经刺激。 虽然科学和临床证据令人鼓舞，但用于进行这些研究的 VNS 设备还不够成熟。 很大程度上受到不灵活的刺激模式、铅脆性、有限的电池寿命、大尺寸和高 成本。这些技术限制阻碍了这种潜在变革疗法的有效转化。我们 开发了一种新型低成本、临床级 VNS 系统，可以克服这些缺陷。系统 由放置在迷走神经上的微型无线、无引线、被动植入刺激器组成 控制植入式刺激器的外部电源和通信模块。植入式装置 采用自动化工艺在晶圆级制造，所用材料经 FDA 批准用于人体 与 MRI 兼容，因此提供可靠性并将成本比市售产品降低 25 倍 设备。植入式刺激器密封封装在生物相容性玻璃中，尺寸缩小了 50 倍 比现有的 VNS 设备，减少了植入手术的侵入性。此外，植入的装置是 无源并从外部模块获取电力，无需笨重的植入电池 手术修复以更换电池。大部分所需测试已完成，但最终验证和 验证对于允许 IDE 提交和临床评估是必要的。 在本提案中，我们概述了一系列关键步骤，以将这种强大、经济高效的设备转化为提供 中风患者的生活得到切实改善。在UG3阶段，我们将完成验证和确认 嵌入式软件并创建设计历史文件。此外，我们将确认生物相容性 长期大型动物研究并完成包装无菌测试。一旦完成，我们将获得批准 IDE。在UH3阶段，我们将进行双盲、随机、安慰剂对照交叉研究 评估慢性中风患者的 VNS 治疗系统。该项目的顺利完成将推动 设备即将转化为人体试验，并直接关注随后的关键试验。