Phase I safety study for a new two-shank auditory midbrain implant (AMI)

新型双柄听觉中脑植入物 (AMI) 的 I 期安全性研究

• 批准号: 8671663
• 负责人: Thomas Lenarz
• 金额: $ 54.19万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-05 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8671663
• 关键词: Acoustic Nerve; Acoustic Neuroma; Acoustic Stimulation; Adverse effects; Animals; Auditory; Auditory Brain Stem Implants; Awareness; Brain; Brain Stem; Bypass; Cadaver; Cell Nucleus; Clinic; Clinical; Clinical Research; Clinical Trials; Cochlea; Cochlear Implants; Cochlear nucleus; Complex; Cues; Deep Brain Stimulation; Devices; Electric Stimulation; Electrodes; Evaluation; Excision; Exhibits; FDA approved; Germany; Head; Hearing; Hearing Impaired Persons; Human; Implant; Individual; Inferior Colliculus; Lead; Life; Lipreading; Midbrain structure; Monitor; Nerve Fibers; Neurofibromatosis 2; Operative Surgical Procedures; Outcome; Patients; Pattern; Performance; Phase; Phase II/III Trial; Positioning Attribute; Probability; Process; Prosthesis; Psychophysics; Quality of life; Refractory; Risk; Safety; Site; Speech; Speech Perception; Stimulus; Structure; Surgeon; Target Populations; Testing; Time; base; commercialization; design; electric impedance; implantable device; implantation; improved; nervous system disorder; public health relevance; restoration; safety study; speech processing; success; transmission process; tumor

DESCRIPTION (provided by applicant): The cochlear implant has achieved remarkable success in restoring hearing to deaf individuals through electrical stimulation of remaining nerve fibers near the cochlea. Unfortunately, cochlear implants are ineffective for those without a functional auditory nerve or implantable cochlea required for implementation. For these individuals, the only option is central auditory stimulation and the only FDA-approved device is the auditory brainstem implant (ABI), which is designed for stimulation of the cochlear nucleus. The ABI is mostly implanted in neurofibromatosis type 2 (NF2) patients who already have to undergo open head surgery to remove a tumor at the brainstem level and become deaf due to tumor-related damage of the auditory nerves. Although the ABI provides hearing improvements to these patients on a daily basis, it generally does not provide sufficient speech perception. One hypothesis is that the tumor removal process may damage brainstem structures crucial for speech understanding that can no longer be effectively activated with the ABI. To bypass this damaged region, a new auditory midbrain implant (AMI) was developed to stimulate in a higher structure, the inferior colliculus (IC). The IC has a well-defined tonotopic organization and is more surgically accessible than the cochlear nucleus, making it a favorable target for a new auditory implant. In a previous clinical trial, five NF2 patients were implanted with a single-shan array AMI device, which has shown to be safe and reliable for over six years. However, none of the patients have achieved sufficient speech understanding. Proceeding animal and human studies have identified the need for a new two-shank array that can more effectively activate across the three-dimensional IC structure. An improved surgical approach has also been developed for more consistently positioning the two-shank array into appropriate regions of the IC. The proposed project is a Phase I clinical study with the primary objective to demonstrate the safety and consistency of implantation and stimulation of this new two-shank AMI device in five NF2 patients at the leading auditory implant center in Germany. The secondary objective is to then show that this new implant can significantly improve hearing performance compared to the single-shank AMI and current ABI devices. To justify implantation of this new AMI device, only patients who have already been implanted with an ABI and achieve no or minimal benefit will be selected for this study. In other words, the AMI is their only hearing option. Each patient will be closely monitored across 8 to 10 testing sessions over a two year period to confirm the safety and reliability of the device over time. Various evaluations, speech tests, and psychophysical tests will also be performed to assess hearing performance with the AMI and to improve the stimulation strategies. Achieving the objectives of this study will justify proceeding Phase II/III trials and hopefully lead to commercialization of an improved central auditory prosthesis to benefit thousands of deaf patients worldwide.

描述（由申请人提供）：通过电刺激耳蜗附近的剩余神经纤维，人工耳蜗植入体在恢复聋人听力方面取得了显著成功。不幸的是，耳蜗植入物对于那些没有功能性听觉神经或实施所需的可植入耳蜗的人是无效的。对于这些人来说，唯一的选择是中央听觉刺激，唯一获得FDA批准的设备是听觉脑干植入物（ABI），它被设计用于刺激耳蜗核。ABI主要植入2型神经纤维瘤病（NF 2）患者，这些患者已经接受了开放式头部手术，以切除脑干水平的肿瘤，并由于肿瘤相关的听觉神经损伤而失聪。虽然ABI每天都能改善这些患者的听力，但它通常不能提供足够的言语感知。一种假设是，肿瘤切除过程可能会损害脑干结构的关键语言理解，不能再有效地激活与ABI。为了绕过这个受损的区域，开发了一种新的听觉中脑植入物（AMI），以刺激更高的结构，下丘（IC）。IC具有明确的音调组织，并且比耳蜗核更容易通过手术进入，使其成为新的听觉植入物的有利目标。在之前的临床试验中，5名NF 2患者植入了单轴阵列AMI设备，该设备已被证明安全可靠超过6年。然而，没有一个患者获得足够的言语理解。动物和人体研究表明，需要一种新的双柄阵列，可以更有效地激活整个三维IC结构。还开发了一种改进的手术方法，用于更一致地将双柄阵列定位到IC的适当区域中。申报项目是一项I期临床研究，主要目的是在德国领先的听觉植入中心证明该新型双柄AMI器械在5名NF 2患者中植入和刺激的安全性和一致性。次要目的是证明与单柄AMI和当前ABI器械相比，这种新型植入物可以显著改善听力性能。为了证明植入这种新的AMI器械的合理性，本研究仅选择已经植入ABI且未获得受益或受益极小的患者。换句话说，AMI是他们唯一的听力选择。每个患者 将在两年内的8至10个测试阶段中进行密切监测，以确认器械的安全性和可靠性。还将进行各种评估、言语测试和心理物理测试，以评估AMI的听力表现并改善刺激策略。实现本研究的目标将证明进行II/III期试验是合理的，并有望使改进的中央听觉假体商业化，使全球数千名耳聋患者受益。