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

• 批准号: 10190477
• 负责人: Charles C Della Santina
• 金额: $ 59.72万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 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/10190477
• 关键词: 3-Dimensional; Action Potentials; Adult; Adverse event; Affect; Anatomy; Auditory; Authorization documentation; Bilateral; Brain; Chronic; Clinical; Cochlear Implants; Cochlear implant procedure; Conscious; Consent; Data; Databases; Devices; Disabled Persons; Dizziness; Ear; Effectiveness; Electric Stimulation; Ensure; Equilibrium; Esthesia; Exhibits; Feasibility Studies; Foundations; Future; Gait; Grant; Hair Cells; Head; Head Movements; Hearing; Implant; Individual; Institutional Review Boards; Investigation; 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; 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; rehabilitation strategy; response; standard of care; vestibulo-ocular reflex; volunteer

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.

项目摘要 双侧前庭感觉丧失是致残的，受影响的个体患有慢性平衡失调， 福尔斯跌倒的风险增加，并且在日常生活中典型的头部运动期间无法保持稳定的视力。而 大多数轻度损失的人通过恢复策略来补偿其他感官， 无法弥补的严重损失没有良好的治疗选择。当前庭神经 在解剖学上完整的，如在大多数这样的情况下，编码头部旋转的电刺激可以驱动神经 活动和部分恢复前庭感觉，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，六名成年人因双侧前庭功能障碍而残疾， 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可行的，安全的和有效的 耳毒性丧失的治疗，如可靠地引起的定向前庭眼反射所证明的 在连续使用3年以上期间，姿势和步态表现的客观指标得到改善，以及 改善患者报告头晕障碍和前庭相关残疾。在那些力量 结果，美国食品和药物管理局（FDA）已邀请人道主义设备的请求 耳毒性丧失治疗的豁免;然而，FDA建议需要额外的数据， 支持扩大这种治疗的可及性，以个人与特发性损失，谁构成了最大的 双侧前庭功能减退的比例。利用完善的设计，完整的研究团队， 以及在耳毒性丧失受试者的早期可行性研究中产生高度影响结果的方案， 拟议的研究计划将扩大这种方法，以成人残疾的特发性成人发病的双边 前庭功能减退这项研究的结果极有可能产生广泛、持续的影响， 通过支持早期监管批准（如果前庭植入治疗特发性丧失的结果 与已经获得的耳毒性丧失的结果一样有利）或通过提供必要的基础 数据，以支持设计一个后续的，大规模的关键试验前庭植入特发性损失。