SWITCH Trial: Early Feasibility Study of Stentrode BCI for Augmentative Communication

7.项目摘要 多项早期人类可行性试验表明，植入式脑机接口（BCI）可以使 严重瘫痪的人使用神经信号来控制远程和数字通信技术，包括 消息和电子邮件。这些研究已经清楚地表明，脑机接口有潜力改善生活质量的人， 因言语和上肢瘫痪而导致身体残疾的患者。然而，在这些技术 商业化后，BCI的使用将仍然限于参与研究的人员，并且仅限于他们的研究期间。 入组研究。为了解决这一未满足的需求，Synchron，Inc.开发了StentrodeTM系统，一个完全 可植入BCI，其与移动的计算平台上的外部接口进行无线通信。StentrodeTM BCI是一种集成到自扩张支架样基底中的16通道传感器阵列。StentrodeTM已交付 通过导管在血管内到达上级窦，在那里它测量来自 两侧大脑半球的腿部运动皮层。一个完全可植入的无线遥测装置将 将神经信号从StentrodeTM传输到外部移动的处理器，该处理器将神经信号转换为命令， 操作计算机或其他辅助设备，如用于交流的拼写器。Synchron团队已经启动了 在澳大利亚墨尔本进行的StentrodeTM脑机接口系统的首次人体试验，获得了治疗学委员会的批准。 澳大利亚商品管理局（TGA）和皇家墨尔本医院IRB。第一个人体植入物是 2019年8月在肌萎缩侧索硬化症（ALS）患者中进行。受试者未出现不良反应 事件，并使用该系统来操作计算机和键入消息给朋友，家人和护理人员。 拟议研究的目的是在早期可行性研究（EFS）中证明StentrodeTM BCI 通信系统是安全和有效的，在独立性和生活质量方面提供了可量化的改善， n=6例因ALS而严重瘫痪的患者。提出了两个具体目标：1）StentrodeTM的临床前评估 完成FDA提交的安全性和功能性测试; 2）在EFS中测试StentrodeTM的安全性和有效性 在美国的两个卓越中心进行临床试验。在目标1（UG 3阶段）下，临床前安全性研究和软件 将在大型动物研究中完成确认，以测试StentrodeTM的稳健性， III类机电植入物，大型动物模型中的安全性和基线功能，定制的有效性 软件和功能性神经影像学研究，以支持术前计划。根据目标2（UH 3阶段），一项EFS研究 将测试StentrodeTM置入的安全性、监测不良事件、目标通畅性和器械移位。组合时 有了眼动追踪技术，用户将被训练用眼睛注视来控制光标来完成基于计算机的任务 位置和BCI输出，以控制离散操作，如字母或菜单项选择和缩放。临床疗效 结果将评估通过使用个人设备恢复独立功能，包括技术能力（点击 和打字速度和准确性，智能家居，物联网，触觉反馈），独立的家庭功能（I-ADL）和QOL 心理健康（WHOQOL，MacGill QOL，HADS）。

7. Project Summary Multiple early feasibility trials in humans have demonstrated that implantable Brain-Computer Interfaces (BCIs) can enable people with severe paralysis to use neural signals to control remote and digital communication technologies, including messaging and email. Such studies have demonstrated clearly that BCIs have the potential to improve the quality of life of patients who have physical disability due to paralysis of speech and upper limbs. However, until these technologies are commercialized, access to BCIs will remain limited to people involved in research studies, and only for the duration of their enrolment in the study. To address this unmet need, Synchron, Inc. has developed the StentrodeTM system, a fully implantable BCI that communicates wirelessly to an external interface on a mobile computing platform. The StentrodeTM BCI is a 16-channel array of sensors integrated into a self-expanding, stent-like substrate. The StentrodeTM is delivered endovascularly via a catheter to the Superior Sagittal Sinus, where it measures volitionally-modulated neural signals from the leg area of motor cortex in both hemispheres. A fully implantable, wireless telemetry unit digitizes and transmits the neural signals from the StentrodeTM to an external mobile processor that converts the neural signals into commands for operating a computer or other assistive device, such as a speller for communication. The Synchron team has already initiated a first-in-human trial of the StentrodeTM BCI system in Melbourne, Australia, under approvals granted by the Therapeutic Goods Administration (TGA) of Australia and the IRB of the Royal Melbourne Hospital. The first human implant was performed in a person with amyotrophic lateral sclerosis (ALS) in August, 2019. The participant has experienced no adverse events and is using the system to operate a computer and type messages to friends, family, and caregivers. The objective of the proposed research is to demonstrate in an Early Feasibility Study (EFS) that the StentrodeTM BCI communication system is safe and effective in providing a quantifiable improvement in independence and quality of life in n=6 people with severe paralysis due to ALS. Two Specific Aims are proposed: 1) Preclinical assessment of the StentrodeTM for safety and functionality to complete an FDA submission, and 2) Testing of StentrodeTM’s safety and efficacy in an EFS clinical trial in two centers of excellence in the USA. Under Aim 1 (UG3 phase), preclinical safety studies and software validation in large animal studies will be completed to test robustness of StentrodeTM, compliance to safety standards for Class III electromechanical implants, safety and baseline functionality in a large animal model, efficacy of custom-built software, and a functional neuroimaging study to support presurgical planning. Under Aim 2 (UH3 phase), an EFS study will test safety of StentrodeTM placement, monitoring adverse events, target patency, and device migration. When combined with eye-tracking technology, users will be trained to perform computer-based tasks using eye-gaze to control cursor position and BCI outputs to control discrete actions, such as letter or menu-item selection and zoom. Clinical efficacy outcomes will assess the restoration of independent function by use of personal devices, including technical capability (click and typing speed and accuracy, smart home, IoT, haptic feedback), independent domestic functionality (I-ADLs) and QOL and mental wellbeing (WHOQOL, MacGill QOL, HADS).