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: 8832723
• 负责人: Thomas Lenarz
• 金额: $ 35.52万
• 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/8832723
• 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; Health; 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; 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）：人工耳蜗通过电刺激耳蜗附近的剩余神经纤维，在恢复聋哑人的听力方面取得了显着的成功。不幸的是，人工耳蜗对于那些没有功能性听觉神经或植入所需的植入式耳蜗的人来说是无效的。对于这些人来说，唯一的选择是中枢听觉刺激，唯一获得 FDA 批准的设备是听觉脑干植入物 (ABI)，它是为刺激耳蜗核而设计的。 ABI 主要植入 2 型神经纤维瘤病 (NF2) 患者，这些患者已经必须接受开颅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。尽管 ABI 每天都能改善这些患者的听力，但它通常无法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对语音理解至关重要的脑干结构，而 ABI 无法再有效地激活这些结构。为了绕过这个受损区域，开发了一种新的听觉中脑植入物（AMI）来刺激更高的结构，即下丘（IC）。 IC 具有明确的音位组织，并且比耳蜗核更容易通过手术接近，使其成为新听觉植入物的有利目标。在之前的临床试验中，五名 NF2 患者植入了单通道 AMI 装置，六年多的时间证明该装置安全可靠。然而，没有一个患者能够获得足够的言语理解能力。正在进行的动物和人类研究已经确定需要一种新的两柄阵列，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，以便更一致地将双柄阵列定位到 IC 的适当区域。拟议项目是一项 I 期临床研究，主要目的是在德国领先的听觉植入中心的 5 名 NF2 患者中证明这种新型双柄 AMI 装置植入和刺激的安全性和一致性。第二个目标是证明与单柄 AMI 和当前的 ABI 设备相比，这种新型植入物可以显着提高听力性能。为了证明植入这种新型 AMI 装置的合理性，只有已经植入 ABI 且没有获益或获益最小的患者才会被选择参加本研究。换句话说，AMI 是他们唯一的听力选择。每个病人 将在两年内通过 8 至 10 次测试进行密切监控，以确认该设备随时间推移的安全性和可靠性。还将进行各种评估、言语测试和心理物理测试，以评估 AMI 的听力表现并改进刺激策略。实现这项研究的目标将证明正在进行的 II/III 期试验是合理的，并有望导致改进的中枢听觉假体的商业化，使全世界数千名聋哑患者受益。