FitMi VNS: the first automated home therapy system for exercise-paired vagus nerve stimulation after stroke

据估计，全世界每6人中就有1人会经历中风，其中50-70%的人会经历慢性中风。 运动障碍虽然密集的运动训练可以部分恢复这些运动功能， 对于个人来说，这种改善往往是不完全的，因为生理过程推动了恢复， 单靠运动训练不足以完全恢复功能。迷走神经刺激（VNS）与 运动训练最近已成为一种有前途的方法，以改善运动恢复， 神经可塑性通过有针对性的释放神经递质。在最近的一项试点研究中， 金伯利等人发现，慢性卒中患者的上肢有较大的临床显著改善， 手动触发运动配对VNS干预后的运动能力， 控制，也证实了在家里提供这种刺激是安全的。然而，手动触发 VNS系统有严重的局限性。首先，运动恢复对刺激时机敏感，但 在临床中用手动触发系统优化刺激定时是不切实际的， 在家里这样做。其次，操作手动触发系统会分散治疗师的注意力， 在治疗期间支持患者。一个自动化的闭环VNS输送系统可以改善这两个方面 运动配对VNS的实用性和治疗效果。因此，对于本直接至第二阶段SBIR，我们 建议完成一个强大的，符合FDA标准的，自动触发的运动配对的开发， VNS系统称为FitMi VNS系统，并测试该系统在临床和 在一个探索性的临床试验与个人慢性中风。本阶段的具体目标 II项目旨在：目标1）完成集成FitMi VNS软件系统，以降低潜在风险， 开发符合HIPAA的远程监控平台;目标2）完成实验室验证， FitMi VNS在慢性卒中患者中的验证测试和监督性体内安全性测试（n = 10）。在这里，我们的目标是>99%的刺激以最佳时机提供，并且没有不良事件 或安全相关问题;以及目标3）完成FitMi VNS的家庭安全性和可行性研究， 慢性脑卒中患者（n = 20）。我们的假设是，FitMi VNS将安全地提供闭环， 在诊所和家中进行运动配对VNS。我们将评估FitiMi VNS的治疗获益 在一项III期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FitMi VNS系统，并在临床上进行初步安全性和可行性测试， 在家里如果成功，FitMi VNS将成为第一个提供自动化闭环锻炼的系统。 配对VNS用于中风康复，导致中风患者运动恢复的阶跃变化。

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.