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: 10330707
• 负责人: SETH ALANSON HAYS
• 金额: $ 116.98万
• 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/10330707
• 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; Placebos; 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; Wireless Technology; 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; 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.

摘要 中风非常普遍，使人衰弱，缺乏持续有效的损伤后干预。我们有 开发了一种创新技术，在康复期间使用迷走神经刺激（VNS）进行 可塑性增强神经调节回路，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，迷走神经刺激与康复训练相结合，可促进多种疾病的恢复。 神经损伤模型，包括缺血性中风、脑内出血、创伤性脑损伤和 脊髓损伤此外，我们最近在慢性中风患者中进行的两项临床研究表明，迷走神经刺激是安全的 与不进行康复治疗相比，上肢功能恢复显着增加三倍 VNS。 虽然科学和临床证据令人鼓舞，但用于执行这些研究的VNS设备 基本上受到不灵活的刺激范例、导线脆弱性、有限的电池寿命、大尺寸和高成本的限制。 成本这些技术限制阻碍了这种潜在的变革性疗法的有效转化。我们 已经开发了一种新型的低成本、临床级VNS系统，其消除了这些缺陷。系统 包括一个微型无线、无导线、无源植入式刺激器，放置在迷走神经上， 控制所述可植入刺激器的外部电源和通信模块。植入式设备 是在晶圆级制造的，使用自动化工艺，材料是FDA批准的人类 使用和MRI兼容，从而提供可靠性和降低成本25倍，相比市售 装置.植入式刺激器密封在生物相容性玻璃中，体积小50倍 与现有的VNS装置相比，减少了植入手术的侵入性。此外，植入装置 无源并从外部模块获取电力，无需笨重的植入式电池， 电池更换手术翻修。大部分所需的测试已经完成，但最终的验证和 需要进行确认，以便提交IDE和进行临床评价。 在这份提案中，我们概述了一系列关键步骤，以将这种强大的、具有成本效益的设备转化为 中风患者生活的切实改善。在UG3阶段，我们将完成验证和确认 并创建设计历史文件。此外，我们将在一个 慢性大型动物研究并完成包装无菌性试验。一旦完成，我们将获得批准， IDE。在UH3期，我们将进行一项双盲、随机、安慰剂对照交叉研究， 评估VNS治疗系统在慢性脑卒中患者中的应用。该项目的成功完成将推动这一 该设备从翻译到人体试验的边缘，直接关注随后的关键试验。