Micronutrient intervention to reduce noise-induced hearing loss

说明书(申请人提供)：噪声性听力损失(NIHL)是一个重要的临床、社会和经济问题；解决这一重要的健康问题对NIDCD的使命至关重要。我们的“从床边到实验室再到床边”的长期战略计划直接导致了目前的建议，即将干预措施从“床边到床边”转化为“床边到床边”。NIDCD为动物研究提供了十年的资金，使我们能够确定导致NIHL的机制，包括直接机械创伤、与代谢应激相关的自由基以及血流减少。我们现在已经确定了一种微量营养素(抗氧化剂和其他制剂)的组合在预防动物NIHL方面非常有效。这种治疗显著减轻了内耳的感觉细胞死亡和相应的阈值缺陷。这项拟议的研究由一个由基础科学家、耳鼻喉科医生和听力学专家组成的国际团队进行，将在使用真实世界噪音侮辱进行的精心控制的临床试验中证明这种治疗干预在人类中的有效性。具体目标1将通过导致暂时性阈值转移的真实世界噪音侮辱来验证治疗效果；这些研究将重点放在实验室条件下响亮的音乐和军事城市作战训练演习上。具体目标2将验证每天暴露在职业噪音中的人类的治疗效果，包括飞行员和地勤人员经历的飞机噪音，以及餐具工人经历的机器噪音。获得有效的治疗将减少高危人群中听力损失的发展，从而提高数百万人的生活质量，并降低个人、企业和政府机构的医疗成本。因此，需要资金启动一系列第二阶段临床试验，以首次证明这种干预措施在MAN中的有效性。该计划旨在成为21世纪消除NIHL的第一个翻译研究步骤。噪声性听力损失是一个重要的医学、社会和经济问题。我们已经确定了一种治疗方法，可以减少动物内耳细胞死亡和听力损失。这些研究将证明这种治疗方法在人类身上的有效性。这种预防措施将提高数百万暴露在噪声中的人的生活质量，并降低个人、企业和政府机构的医疗成本。

DESCRIPTION (provided by applicant): Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue; resolving this important health issue is central to the mission of the NIDCD. Our long-term strategic program of "bedside to laboratory bench to bedside" directly leads to the current proposal to translate an intervention from "bench to bedside". Ten years of NIDCD funding for studies in animals have allowed us to identify mechanisms contributing to NIHL, including direct mechanical trauma, free radicals formed in association with metabolic stress, and reduced blood flow. We have now identified a combination of micronutrients (antioxidants and other agents) as highly effective in preventing NIHL in animals. This treatment significantly attenuates sensory cell death in the inner ear and corresponding threshold deficits. The proposed studies, conducted by an international team including basic scientists, otolaryngologists, and audiologists, will demonstrate efficacy of this therapeutic intervention in humans during carefully-controlled clinical trials with real-world noise insults. Specific Aim 1 will verify therapeutic efficacy with real-world noise insults that induce temporary threshold shifts; these studies will focus on loud music under laboratory conditions, and military urban warfare training exercises. Specific Aim 2 will verify therapeutic efficacy in humans exposed to occupational noise on a daily basis, including aircraft noise experienced by pilots and ground crew, and machine noise experienced by cutlery workers. Availability of an effective treatment will reduce development of hearing loss in at-risk human populations, thereby improving quality of life for millions and decreasing healthcare costs for individuals, businesses, and government agencies. Funds are therefore requested to initiate a series of Phase II clinical trials to demonstrate for the first time the effectiveness of this intervention in man. This program is intended to be the first translational research step to eliminate NIHL in the 21st century. Noise-induced hearing loss is an important medical, social, and economic issue. We have identified a treatment that reduces inner ear cell death and hearing loss in animals. These studies will demonstrate efficacy of this treatment in humans. This prevention will improve quality of life for the millions exposed to noise, and decrease healthcare costs for individuals, businesses, and government agencies.