FitMi VNS: The First Automated Home Therapy System for Exercise-Paired Vagus Nerve Stimulation After Stroke

FitMi VNS：首个用于中风后运动配对迷走神经刺激的自动化家庭治疗系统

• 批准号: 10413806
• 负责人: Nizan Friedman
• 金额: $ 84.54万
• 依托单位: FLINT REHABILITATION DEVICES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10413806
• 关键词: Activities of Daily Living; Adverse event; Automobile Driving; Chronic; Clinic; Clinical Trials; Computer software; Data; Development; Devices; Event; Exercise; Feasibility Studies; Feedback; Funding; Goals; Hand; Health Insurance Portability and Accountability Act; Home; Impairment; Implant; Individual; Intervention; Leg; Life; Living Standards; Manuals; Measures; Methods; Motor; Movement; Nervous System Trauma; Neuronal Plasticity; Outcome Measure; Participant; Pathway interactions; Patients; Performance; Persons; Phase; Physiological Processes; Pilot Projects; Protocols documentation; Public Health; Randomized; Recovery; Rehabilitation therapy; Research; Risk; Rotation; Safety; Small Business Innovation Research Grant; Societies; Stroke; Supervision; System; Testing; Texas; Therapeutic; Therapeutic Effect; Touch sensation; Training; Translations; United States National Institutes of Health; Universities; Upper Extremity; Vagus nerve structure; arm; base; chronic stroke; clinically significant; cohort; commercialization; design; disability; efficacy study; experience; feasibility testing; functional restoration; improved; improved outcome; in vivo; in vivo evaluation; motor impairment; motor recovery; neurological rehabilitation; neurotransmitter release; novel; post stroke; primary outcome; recruit; remote monitoring; remote patient monitoring; risk mitigation; safety and feasibility; safety study; safety testing; sensor; software systems; stroke rehabilitation; usability; vagus nerve stimulation; verification and validation; wireless

It is estimated that 1 in 6 people worldwide will experience a stroke, with 50-70% experiencing chronic movement impairment. While intensive motor training can partially restore motor function in these individuals, the improvement is often incomplete, as the physiological processes driving recovery through motor training alone are insufficient to fully restore function. Vagus Nerve Stimulation (VNS) paired with motor training has recently emerged as a promising method to improve movement recovery by increasing neuroplasticity through targeted release of neurotransmitters. In a recent pilot study with individuals with chronic stroke, Kimberley et al. found large, clinically significant improvements in upper extremity movement ability following an intervention of manually-triggered exercise-paired VNS compared to control, also confirming that it was safe to deliver this stimulation at home. However, a manually triggered VNS system has critical limitations. First, motor recovery is sensitive to stimulation timing but it is impractical to optimize stimulation timing with a manually-triggered system in the clinic, and impossible to do so at home. Second, operating a manually triggered system distracts therapists from optimally supporting patients during therapy. An automated, closed-loop VNS delivery system could improve both the practicality and therapeutic effects of exercise-paired VNS. Thus, for this Direct-to-Phase II SBIR, we propose to complete development of a robust, FDA compliant, automatically triggered exercise-paired VNS system called FitMi VNS system and to test the safety and usability of this system in the clinic and at home in an exploratory clinical trial with individuals with chronic stroke. Our specific aims for this Phase II project are to: Aim 1) Complete an integrated FitMi VNS software system to mitigate potential risks and develop a HIPAA compliant remote monitoring platform; Aim 2) Complete bench-top verification and validation testing and supervised, in-vivo safety testing of FitMi VNS in individuals with chronic stroke (n = 10). Here, our goal is for >99% of stimulations to be delivered with optimal timing and no adverse events or safety-related issues; and Aim 3) Complete an at-home safety and feasibility study of FitMi VNS in individuals with chronic stroke (n = 20). Our hypothesis is that FitMi VNS will safely provide closed-loop, exercise-paired VNS both in the clinic and at home. We will evaluate the therapeutic benefit of FitiMi VNS in a large scale randomized controlled efficacy study in Phase III. At the end of this project, we will have rigorously refined the FitMi VNS system and performed initial safety and feasibility testing in the clinic and at home. If successful, FitMi VNS will be the first system to provide automated, closed-loop exercise- paired VNS for stroke rehabilitation, leading to a step change in motor recovery for individuals with stroke.

据估计，全世界每6个人中就有1个人会中风，其中50%-70%的人会经历慢性中风 运动障碍。而强化运动训练可以部分恢复这些患者的运动功能 对于个体来说，这种改善往往是不完整的，因为生理过程通过 仅靠运动训练不足以完全恢复功能。迷走神经刺激(VNS)与 运动训练最近被认为是一种很有希望的方法，通过增加 通过定向释放神经递质来实现神经可塑性。在最近一项针对患有抑郁症的个人的初步研究中 慢性卒中，金伯利等人。发现上肢有很大的临床显著改善 手动触发运动配对VNS干预后的运动能力比较 控制，也证实了在家中提供这种刺激是安全的。然而，手动触发的 VNS系统有严重的局限性。首先，运动恢复对刺激时机很敏感，但它是 在临床上用手动触发系统来优化刺激时机是不现实的，也是不可能的 在家里做到这一点。其次，操作手动触发的系统分散了治疗师对最佳治疗的注意力 在治疗过程中支持患者。一个自动化的、闭环的VNS交付系统可以改善这两个方面 运动配对迷走神经的实用性和治疗效果。因此，对于这一直接到第二阶段的SBIR，我们 建议完成强大的、符合FDA的、自动触发的运动配对的开发 VNS系统称为FitMi VNS系统，并在临床和临床上测试了该系统的安全性和可用性 在一项针对慢性中风患者的探索性临床试验中。我们在这一阶段的具体目标 第二个项目是：目标1)完成一个集成的FitMi VNS软件系统，以减轻潜在风险和 开发符合HIPAA标准的远程监控平台；目标2)完成台式验证和 FitMi VNS在慢性卒中患者(N)中的有效性测试和监督体内安全性测试 =10)。在这里，我们的目标是在最佳时机和无不良事件的情况下提供99%的刺激 或与安全相关的问题；以及Aim 3)完成FitMi VNS在 慢性卒中患者(n=20)。我们的假设是，FitMi VNS将安全地提供闭环， 无论是在诊所还是在家里，都可以锻炼成对的VNS。我们将评估FitiMi VNS的治疗效果 在第三阶段的大规模随机对照疗效研究中。在这个项目结束时，我们将有 严格改进了FitMi VNS系统，并在临床和 在家。如果成功，FitMi VNS将成为第一个提供自动化、闭环系统演习的系统- 用于中风康复的配对VNS，导致中风患者运动恢复的阶梯变化。