Vestibular Implantation to Treat Adult-Onset Bilateral Vestibular Hypofunction

前庭植入治疗成人发病的双侧前庭功能减退症

基本信息

批准号：
10625287
负责人：
Charles C Della Santina
金额：
$ 55.77万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-21 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10625287
关键词：
3-Dimensional Action Potentials Adult Adverse event Affect Anatomy Auditory Authorization documentation Bilateral Brain Chronic Clinical Cochlear Implants Cochlear implant procedure Compensation Conscious Consent Data Databases Devices Disabled Persons Dizziness Ear Effectiveness Electric Stimulation Ensure Equilibrium Esthesia Exclusion Exhibits Feasibility Studies Foundations Future Gait Grant Hair Cells Head Head Movements Hearing Implant Individual Institutional Review Boards Laboratories Labyrinth Life Longterm Follow-up Measures Medical Device Medicine Monitor Motion Multicenter Trials National Institute on Deafness and Other Communication Disorders Nerve Noise Operative Surgical Procedures Outcome Patients Performance Persons Posture Procedures Prosthesis Protocols documentation Recruitment Activity Regulation Rehabilitation therapy Reporting Research Research Design Research Project Grants Rotation Running Safety Sample Size Sampling Scientific Inquiry Semicircular canal structure Signs and Symptoms Solid Stimulus Study Subject Swimming System Technology Testing Therapeutic Thinking United States United States Food and Drug Administration Vestibular Nerve Vestibular loss Vision Walking Work cell injury clinical investigation cognitive load cohort cost design disability effective therapy effectiveness evaluation efficacy evaluation experience fall risk falls first-in-human follow-up health related quality of life hearing impairment implantation improved inclusion criteria ototoxicity patient population posture instability power analysis programs prospective response standard of care vestibulo-ocular reflex volunteer

项目摘要

Project Summary Bilateral loss of vestibular sensation is disabling, with affected individuals suffering chronic disequilibrium, increased risk of falls, and inability to maintain stable vision during head movements typical of daily life. While most individuals with milder loss compensate through rehabilitative strategies enlisting other senses, those with severe loss who fail to compensate have no good therapeutic options. When the vestibular nerves are anatomically intact, as is true in most such cases, electrical stimuli encoding head rotation can drive nerve activity and partially restore vestibular sensation, much as a cochlear implant partially restores auditory sensation. In an on-going first-in-human early feasibility study of six adults disabled by bilateral vestibular hypofunction after ototoxic hair cell injury, we found that vestibular implantation and motion-modulated prosthetic stimulation targeting the implanted ear's three semicircular canals is a feasible, safe and effective treatment for ototoxic loss, as evidenced by directionally-aligned vestibulo-ocular reflexes reliably elicited during >3 years of continuous use, improvements in objective measures of posture and gait performance, and improvement of patient-reported dizziness handicap and vestibular-related disability. On the strength of those results, the United States Food & Drug Administration (FDA) has invited a request for humanitarian device exemption for treatment of ototoxic loss; however, FDA advised that additional data would be required to support expanding availability of this treatment to individuals with idiopathic loss, who make up the largest proportion of bilateral vestibular hypofunction cases. Drawing on a well-established design, intact study team, and protocol that yielded highly impactful results in the early feasibility study of subjects with ototoxic loss, the proposed research program will extend this approach to adults disabled by idiopathic adult-onset bilateral vestibular hypofunction. Results of this research are highly likely to yield broad, sustained impact, either through support of early regulatory approval (if results of vestibular implantation for treatment of idiopathic loss are as favorable as the results already obtained for ototoxic loss) or by providing the necessary foundational data to support design of a subsequent, large-scale pivotal trial of vestibular implantation for idiopathic loss.

项目概要双侧前庭感觉丧失会导致失能，受影响的个体会遭受慢性失衡，跌倒的风险增加，并且在日常生活中典型的头部运动时无法保持稳定的视力。尽管大多数损失较轻的人通过利用其他感官的康复策略来补偿，损失严重且无法补偿的人没有良好的治疗选择。当前庭神经处于在解剖学上完好无损，就像大多数此类情况一样，编码头部旋转的电刺激可以驱动神经活动并部分恢复前庭感觉，就像人工耳蜗部分恢复听觉一样感觉。在一项正在进行的首次人体早期可行性研究中，研究对象是六名因双侧前庭功能障碍而致残的成年人耳毒性毛细胞损伤后功能减退，我们发现前庭植入和运动调节针对植入耳的三个半规管的假体刺激是一种可行、安全、有效的方法耳毒性损失的治疗，通过可靠引发的定向排列的前庭眼反射来证明在连续使用超过 3 年期间，姿势和步态表现的客观测量得到改善，以及改善患者报告的头晕障碍和前庭相关障碍。靠那些人的力量结果，美国食品和药物管理局 (FDA) 已发出人道主义设备请求耳毒性损失治疗的豁免；然而，FDA 建议需要额外的数据支持将这种治疗的可及性扩大到特发性丧失患者，他们是最大的特发性丧失患者双侧前庭功能减退病例的比例。借鉴完善的设计、完整的研究团队，和在耳毒性损失受试者的早期可行性研究中产生高度影响的结果的协议，拟议的研究计划将把这种方法扩展到因特发性成人发病双侧残疾而致残的成年人前庭功能减退。这项研究的结果很可能产生广泛、持续的影响通过早期监管批准的支持（如果用于治疗特发性丢失的前庭植入的结果与已经获得的耳毒性损失结果一样有利）或通过提供必要的基础数据支持后续大规模关键性前庭植入治疗特发性缺失试验的设计。