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

• 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
• 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

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.

摘要 噪声是头号职业危害和环境危害，而噪声- 诱发性听力损失(NIHL)是感音神经性听力障碍的一种常见形式，仅 其次是与年龄相关的听力损失。目前，没有预防NIHL的药物获得美国食品和药物管理局批准 美国食品和药物管理局(FDA)。美国政府面临的一大挑战 引入这种干预措施的需要是确定适当的人类人口 可用于评估新的耳保护剂的效果。 在这个STTR第一阶段项目中，我们建议确定听力损失的程度 在以颅骨为基础的手术中，患者在未手术的耳朵中钻孔。基于我们的 初步研究，我们已经降低了检测耳蜗术的变异性 听力损失。通过与华盛顿大学学院的合作者合作 在圣路易斯的医学中心，在三个病人中有两个检测到了颞叶听力 以颅骨为基础的手术后，未手术的耳朵的阈值发生了变化。最近的一部开创性作品 在动物身上的发现表明，即使没有永久性的阈值转移， 内耳内毛细胞和螺旋神经节神经元之间的突触是 NIHL的原发病理。这种形式的突触丢失被称为耳蜗性突触， 或者隐匿性听力损失。到目前为止，还没有纵向研究报告证实 人群中存在隐性听力损失，尽管两项人类研究表明 通过比较噪声风险不同的人群发现耳蜗性突触病变的可能性 曝光。在这里，我们将继续招募符合条件的患者进行颅脑手术 做手术。功能测试，如听力测试、耳蜗电、失真 产品耳声发射，以及多人讲话的噪声中单词测试将 在手术前、手术后一天和一个月后在未手术的耳朵上重复- 做手术。到项目结束时，我们预计将量化临时和 患者的永久性阈值移动；并确认存在隐性听力损失 这些志愿者中有一定比例。本研究的主要创新之处在于 在类似实验室的环境下确定不可避免地暴露在噪音中的新人群 使用改进的功能分析。如果成功，在STTR或SBIR第二阶段项目中， 我们将根据这一人群进行FDA批准的临床试验(NCT02049073)。 因此，该项目不仅将为未来的新的临床研究确定新的人群 耳保护剂，但也是第一次对隐匿性听力损失的流行病学研究 人口。我们的长期目标是为NIHL开发一种有效的医学干预措施。