An unique patient population for clinical trials against noise-induced hearing loss

针对噪音引起的听力损失进行临床试验的独特患者群体

基本信息

批准号：
10006932
负责人：
Jianxin Bao
金额：
$ 9.99万
依托单位：
GATEWAY BIOTECHNOLOGY, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10006932
关键词：
Adult Age Air American Animals Auditory Behavior Therapy Biological Assay Clinical Clinical Research Clinical Trials Conduct Clinical Trials Control Groups Ear Effectiveness Electrocochleographies Environment Environmental Hazards Environmental Risk Factor Ethics Exposure to Future Goals Health Hearing Hearing Tests Human Inner Hair Cells Intervention Laboratories Labyrinth Lead Longitudinal Studies Measurement Medical Military Personnel Music Neurons Noise Noise-Induced Hearing Loss Operative Surgical Procedures Participant Pathology Patient Schedules Patients Pharmaceutical Preparations Pharmacotherapy Phase Population Population Sizes Presbycusis Reporting Reproducibility Risk Seminal Side Small Business Innovation Research Grant Small Business Technology Transfer Research Synapses Temporary Threshold Shift Testing United States Department of Veterans Affairs United States Food and Drug Administration Universities Washington base bone cochlear synaptopathy cohort cost cranium epidemiology study hearing impairment hearing threshold hidden hearing loss high risk improved innovation medical schools normal hearing occupational hazard otoacoustic emission otoprotectant patient population phase 2 study preclinical study prevent public health relevance recruit skull base sound spiral ganglion volunteer

项目摘要

Abstract Noise is the number one occupational and environmental hazard, and noise- induced hearing loss (NIHL) is one common form of sensorineural hearing deficit, only second to age-related hearing loss. Currently no drug preventing NIHL is approved by the United States Food and Drug Administration (FDA). One major challenge for the introduction of such interventions is the need to identify appropriate human populations available for evaluating the effectiveness of new otoprotective agents. In this STTR Phase I project, we propose to determine the extent of hearing loss in unoperated ears of patients after drilling during skull-based surgery. Based on our preliminary studies, we have reduced the variability of electrocochleography for detecting hearing loss. By working with our collaborators at Washington University School of Medicine in St. Louis, in two out three patients, we have detected temporal hearing threshold shifts in unoperated ears after the skull-based surgery. A recent seminal discovery in animals revealed that, even without permanent threshold shift, a loss of synapses between inner hair cells and spiral ganglion neurons in the inner ear is the primary pathology for NIHL. This form loss of synapses is called cochlear synaptopathy, or hidden hearing loss. So far, no longitudinal studies have been reported to confirm the existence of hidden hearing loss in people although two human studies implicated possibility of cochlear synaptopathy by comparing groups with different risks for noise exposure. Here, we will continue to recruit qualified patients scheduled for skull-based surgery. Functional assays, such as audiometric testing, electrocochleography, distortion product otoacoustic emissions, and the Words-in-Noise test with multi-talker babble will be repeated on their unoperated ears before the surgery, one day and one-month post- surgery. By the project’s end, we expect to quantify the extent of both temporary and permanent threshold shift in patients; and confirm the existence of hidden hearing loss in a certain percentage of these volunteers. The main innovative aspect of this study is to identify a new population with unavoidable noise exposure under a laboratory-like setting using improved functional assays. If successful, In the STTR or SBIR Phase II project, we will carry our FDA-approved clinical trial (NCT02049073) based on this population. Thus, this project will not only identify a new population for future clinical studies of new otoprotective agents, but also the first epidemiological study of hidden hearing loss in this population. Our long-term goal is to develop an effective medical intervention for NIHL.

抽象的噪声是第一大职业危害和环境危害，噪声诱发性听力损失 (NIHL) 是感音神经性听力缺陷的一种常见形式，仅仅次于年龄相关性听力损失。目前，还没有批准预防 NIHL 的药物。美国食品和药物管理局 (FDA) 面临的一项重大挑战。引入此类干预措施需要确定适当的人群可用于评估新型耳保护剂的有效性。在这个 STTR 第一阶段项目中，我们建议确定听力损失的程度根据我们的研究，在颅骨手术期间钻孔后的未手术患者的耳朵中。初步研究，我们减少了用于检测的耳蜗电图的变异性通过与华盛顿大学学院的合作者合作。圣路易斯医学中心，在三分之二的患者中，我们检测到颞部听力最近一项开创性的颅骨手术后未手术耳朵的阈值变化。在动物身上的发现表明，即使没有永久性的阈值变化，内耳内毛细胞和螺旋神经节神经元之间的突触是 NIHL 的主要病理学是这种形式的突触丧失，称为耳蜗突触病。或隐性听力损失，到目前为止，还没有纵向研究证实这一点。尽管两项人体研究表明人们存在隐性听力损失通过比较具有不同噪声风险的群体来确定耳蜗突触病的可能性在这里，我们将继续招募符合条件的患者，安排进行颅骨暴露。功能测定，例如听力测试、耳蜗电图、失真。产品耳声发射，以及多说话者胡言乱语的噪声词测试将在手术前、手术后一天和一个月后在未手术的耳朵上重复进行到项目结束时，我们希望量化临时和手术的范围。患者的永久性阈值偏移；并确认患者存在隐性听力损失。这项研究的主要创新点是这些志愿者中的一定比例。在类似实验室的环境下识别不可避免的噪音暴露的新人群如果成功的话，在 STTR 或 SBIR 第二阶段项目中，使用改进的功能测定。我们将针对这一人群开展 FDA 批准的临床试验 (NCT02049073)。因此，该项目不仅将确定新的人群用于未来的临床研究耳保护剂，也是本领域第一项隐性听力损失的流行病学研究我们的长期目标是针对 NIHL 开发有效的医疗干预措施。