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

呼吸道并发症是宫颈及高压病患者的显著发病率和死亡率。 胸段脊髓损伤(SCI)是由于他们不能咳嗽所致。因此，大多数人都患有 清除呼吸道分泌物的能力显著降低，导致反复呼吸道的发展 感染1-16、128-130、132、135、136此外，呼吸系统疾病是导致本病死亡的主要原因 3、7、9、12、15这些人由于肌肉瘫痪而缺乏有效的咳嗽机制 18-20，42,126-130,132,135,136我们已经进行了一项试点临床试验(n=17)，使用圆盘电极和 证明在SCI.27-29中可以恢复有效的咳嗽。这种方法产生接近最大呼气的呼气 肌肉激活，如大气道压力和最大呼气气流速度的产生所反映的， 与正常人最大咳嗽时观察到的范围相同。27，28使用 该系统显著降低了分泌物的增加难度，降低了呼吸道的发病率。 感染29,117不幸的是，放置盘状电极需要一种侵入性的外科手术。在最近一次 使用平行线电极(T9-T11脊柱水平)的双极SCS的临床试验，我们证明了可比性 与椎间盘相比，可以实现呼气肌激活水平和临床益处 电极119,120,121a，153我们目前的刺激系统需要使用由 Ardiem(印第安纳州，宾夕法尼亚州)和Finetech，Inc.(英格兰伦敦)的电刺激器(FM)。然而，FM并非如此 有蓝牙功能，天线笨重，没有许可证允许美国 商业化。因此，我们计划与艾弗里生物医疗设备公司(纽约州科马克)合作 构建更先进、更人性化的刺激器。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 并且天线非常灵活，不需要定向。此外，ABD已经提供了服务 有呼吸道护理需求的患者。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。这一装置将是唯一可用于商业用途的脊髓刺激器 具有激活呼气肌和恢复有效咳嗽所需的刺激参数范围。 因此，这项拟议研究的主要目标是：1)构建一个电刺激器来激活 呼气肌并与Ardiem电极连接2)执行必要的测试 FDA将修改我们目前的IDE 3)进行多中心临床试验，以确定有线SCS的效用 导致有效咳嗽，并提供有效清除呼吸道分泌物的方法，减少 脊髓损伤后呼吸道感染的发生率和改善受试者的生活质量4)满足 法规要求获得FDA对该设备的批准，以最终实现商业化。最终，我们 期待这项技术成为脊髓损伤患者常规治疗的重要临床工具。 7.