Multi-Center Clinical Trial of Spinal Cord Stimulation to Restore Cough

脊髓刺激恢复咳嗽的多中心临床试验

• 批准号: 10358346
• 负责人: Anthony F. DiMarco
• 金额: $ 160.85万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10358346
• 关键词: Air Movements; Animals; Atelectasis; Bluetooth; CD2 gene; Caregiver support; Caring; Cause of Death; Cervical; Characteristics; Chest; Clinical; Clinical Trials; Coughing; Data; Development; Devices; Distal; Dorsal; Electric Stimulation; Electrodes; England; Food and Drug Administration Device Approval; Generations; Hemorrhage; Implant; Incidence; Indiana; Individual; Infection; Injury; Lead; Licensing; Life; London; Methods; Morbidity - disease rate; Multi-Institutional Clinical Trial; Multicenter Trials; Muscle; Neurostimulation procedures of spinal cord tissue; Operative Surgical Procedures; Paralysed; Participant; Pathway interactions; Patients; Persons; Plant Roots; Positioning Attribute; Predictive Value; Quality of life; Recurrence; Respiratory Disease; Respiratory System; Respiratory Tract Infections; Risk; Safety; Services; Site; Spinal; Spinal Cord; Spinal cord injury; Sterilization; Stimulus; Surface; Surgical incisions; System; Techniques; Testing; Thoracic spinal cord structure; Time; Ventral Roots; biomaterial compatibility; commercialization; cost effective; expiration; flexibility; improved; minimally invasive; mortality; neuromuscular system; patient population; positive airway pressure; pressure; radio frequency; respiratory; tool; user-friendly; virtual

Respiratory complications account for significant morbidity and mortality in persons with cervical and high thoracic spinal cord injury (SCI) due to their inability to cough. As a consequence, most individuals suffer from a markedly reduced ability to clear airway secretions resulting in the development of recurrent respiratory tract infections.1-16, 128-130,132,135,136 Moreover, diseases of the respiratory system are the leading cause of death in this patient population.3,7,9,12,15 These individuals lack an effective cough mechanism due to paralysis of the muscles of expiration.18-20,42,126-130,132,135,136 We have performed a pilot clinical trial (n=17) with disc electrodes and demonstrated that an effective cough can be restored in SCI.27-29 This method results in near maximal expiratory muscle activation, as reflected by the generation of large airway pressures and peak expiratory airflow rates, which are in the same range as those observed during maximum cough efforts in normal persons.27,28 Use of the system significantly reduces the difficulty in raising secretions and reduces the incidence of respiratory tract infections29,117 Unfortunately, disc electrode placement requires an invasive surgical procedure. In a recent clinical trial of bipolar SCS with parallel wire electrodes (T9–T11 spinal levels), we demonstrated that comparable levels of expiratory muscle activation and clinical benefits can be achieved, when compared to the disc electrodes (n=12).119,120,121a,153 Our current stimulation system entails use of wire electrodes manufactured by Ardiem (Indiana, PA) and electrical stimulator by Finetech, Inc (London, England) (FM). FM however does not have Bluetooth capability, has a cumbersome antenna and does not have a license to allow US commercialization. Therefore, we plan to partner with Avery Biomedical Devices (Commack, NY) (ABD) to construct more advanced and more user-friendly stimulator. The ABD device will have Bluetooth capability allowing for remote activation and facilitate data logging including the ability to view, download and analyze data in real time and the antenna is very flexible with no orientation requirement. In addition, ABD already services patients with respiratory care needs. This stimulator will be used in conjunction with Ardiem wire electrodes, utilized in our recent clinical trial. This device will represent the only commercially available spinal cord stimulator with the range of stimulus parameters required to activate the expiratory muscles and restore an effective cough. The Major Objectives of the proposed study, therefore, are to 1) construct an electrical stimulator to activate the expiratory muscles and connect with the Ardiem electrodes 2) perform the necessary testing required by the FDA to amend our current IDE 3) perform a multi-center clinical trial to determine the utility of SCS with wire leads to produce an effective cough and provide an effective means of clearing airway secretions, reduce the incidence of respiratory tract infections and improve subject quality of life in SCI and 4) meet the necessary regulatory requirements to obtain FDA approval of the device for eventual commercialization. Ultimately, we expect this technique to become an important clinical tool in the routine management of subjects with SCI. 7

呼吸道并发症是颈椎病和高血压患者的显着发病率和死亡率 由于无法咳嗽而导致胸脊髓损伤（SCI）。结果，大多数人都患有 清除气道分泌物的能力明显下降，导致呼吸道反复发作 感染。1-16, 128-130,132,135,136 此外，呼吸系统疾病是该人群死亡的主要原因 患者群体。3,7,9,12,15 这些人由于肌肉麻痹而缺乏有效的咳嗽机制 18-20,42,126-130,132,135,136 我们已经使用圆盘电极和 证明 SCI 中可以恢复有效的咳嗽。27-29 该方法导致接近最大呼气 肌肉激活，如大气道压力和峰值呼气气流速率的产生所反映的， 与正常人最大程度咳嗽时观察到的范围相同。27,28 系统显着降低分泌物升高难度，降低呼吸道疾病发生率 感染29,117 不幸的是，椎间盘电极放置需要侵入性外科手术。在最近的一次 使用平行线电极（T9-T11 脊髓水平）的双极 SCS 的临床试验，我们证明了可比较的 与椎间盘相比，可以实现呼气肌激活水平和临床益处 电极 (n=12).119,120,121a,153 我们的电流刺激系统需要使用由 Ardiem（印第安纳州，宾夕法尼亚州）和 Finetech, Inc（英国伦敦）的电刺激器 (FM)。但 FM 不 具有蓝牙功能，具有笨重的天线，并且没有允许美国的许可证 商业化。因此，我们计划与 Avery Biomedical Devices（纽约州康马克）(ABD) 合作， 构建更先进、更用户友好的刺激器。 ABD 设备将具有蓝牙功能 允许远程激活并促进数据记录，包括查看、下载和分析数据的能力 实时且天线非常灵活，无方向要求。此外，ABD已经提供服务 有呼吸护理需求的患者。该刺激器将与 Ardiem 线电极结合使用， 在我们最近的临床试验中使用。该设备将代表唯一的商用脊髓刺激器 具有激活呼气肌并恢复有效咳嗽所需的刺激参数范围。 因此，拟议研究的主要目标是 1）构建一个电刺激器来激活 呼气肌并连接 Ardiem 电极 2) 执行所需的必要测试 FDA 修改我们当前的 IDE 3) 进行多中心临床试验以确定线 SCS 的效用 导致产生有效的咳嗽并提供清除气道分泌物的有效方法，减少 呼吸道感染的发生率并提高 SCI 受试者的生活质量，4) 满足必要的要求 获得 FDA 批准该设备最终商业化的监管要求。最终，我们 预计该技术将成为 SCI 受试者日常管理的重要临床工具。 7