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

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，在恢复失聪个体听力方面取得了显著的成功。不幸的是，人工耳蜗对于那些没有功能听神经或植入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），这是为刺激耳蜗核而设计的。ABI主要用于2型神经纤维瘤病（NF2）患者，这些患者必须接受开颅手术切除脑干水平的肿瘤，并因肿瘤相关的听神经损伤而失聪。虽然ABI每天为这些患者提供听力改善，但它通常不能提供足够的语言感知。一种假设是，肿瘤切除过程可能会损害对言语理解至关重要的脑干结构，这些结构不能再被ABI有效激活。为了绕过这一受损区域，一种新的听觉中脑植入物（AMI）被开发出来刺激一个更高的结构，下丘（IC）。IC具有明确的同种异位组织，比耳蜗核更容易手术接近，使其成为新的听觉植入物的有利目标。在之前的一项临床试验中，5名NF2患者植入了单山阵列AMI装置，该装置在6年多的时间里证明是安全可靠的。然而，没有一个患者达到足够的言语理解。正在进行的动物和人类研究已经确定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。一种改进的手术方法也被开发出来，可以更一致地将双柄阵列定位到IC的适当区域。拟议的项目是一项I期临床研究，主要目的是在德国领先的听觉植入中心，在五名NF2患者中证明这种新的双柄AMI装置的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和目前的ABI设备相比，这种新的植入物可以显著改善听力。为了证明植入这种新型AMI装置的合理性，本研究只选择已经植入ABI且没有或只有很小获益的患者。换句话说，AMI是他们唯一的听力选择。每个病人

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.