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

呼吸系统并发症是颈椎病和高血压患者的主要发病率和死亡率。 胸部脊髓损伤（SCI），由于他们无法咳嗽。因此，大多数人患有 清除气道分泌物的能力明显降低，导致出现反复呼吸道 1 -16，128- 130，132，135，136此外，呼吸系统疾病是这一领域死亡的主要原因。 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我们进行了一项初步临床试验（n=17），使用圆盘电极， 在SCI中证明了有效的咳嗽可以恢复。27 -29这种方法导致接近最大呼气 肌肉激活，如由大气道压力和峰值呼气气流速率的产生所反映的， 这与正常人在最大咳嗽努力期间观察到的范围相同。27，28 系统大大降低了分泌物提升的难度，降低了呼吸道感染的发生率 感染29，117不幸的是，盘电极放置需要侵入性外科手术。在最近的一 采用平行丝电极（T9-T11脊柱节段）的双极SCS的临床试验，我们证明， 与椎间盘相比， 119，120，121 a，153我们的电流刺激系统需要使用由 Ardiem（印第安纳州，PA）和Finetech，Inc（伦敦，英格兰）的电刺激器（FM）。然而，FM不 有蓝牙功能，有一个笨重的天线，没有许可证，允许我们 商业化因此，我们计划与Avery Biomedical Devices（科马克，纽约州）（ABD）合作， 构建更先进、更人性化的刺激器。ABD器械将具有蓝牙功能 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 在真实的时间内，并且天线非常灵活，没有定向要求。此外，ABD还提供 需要呼吸护理的患者。该刺激器将与Ardiem丝电极配合使用， 在我们最近的临床试验中使用。该器械将代表唯一的市售脊髓刺激器 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，拟议研究的主要目标是：1）构建一个电刺激器， 呼气肌并与Ardiem电极连接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，以确定带导丝的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手段，减少 呼吸道感染的发病率和改善SCI患者的生活质量; 4）满足必要的 法规要求，以获得FDA对器械的最终商业化批准。最终我们 期望这项技术成为SCI患者常规治疗的重要临床工具。 7