Collaborative Tinnitus Research at Washington University

华盛顿大学耳鸣合作研究

• 批准号: 7857556
• 负责人: Jay F. PiccirIllo
• 金额: $ 16.82万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7857556
• 关键词: Adverse effects; Aftercare; American; Area; Auditory area; Brain; Chronic; Clinical; Clinical Trials; Clinical Trials Design; Cognition; Development; Devices; Disabled Persons; Drops; Effectiveness; Engineering; Enrollment; Ensure; Equipment and supply inventories; Fiber; Frequencies; Friends; Future; Genetic Crossing Over; Goals; Hyperactive behavior; Image; Interdisciplinary Study; Knowledge; Literature; Magnetism; Measures; Modality; Neurocognitive; Neurologic; Outcome; Patients; Phenotype; Positron-Emission Tomography; Randomized Controlled Clinical Trials; Reporting; Research; Research Personnel; Research Project Grants; Sample Size; Severities; Stimulus; Subjective Tinnitus; Techniques; Testing; Therapeutic; Tinnitus; Universities; Variant; Washington; active method; cranium; executive function; experience; handicapping condition; magnetic field; neurocognitive test; neuroimaging; novel; programs; psychologic; repetitive transcranial magnetic stimulation; response

DESCRIPTION (provided by applicant): Chronic incapacitating subjective tinnitus is a significant problem for a large number of Americans. Neuroimaging studies have shown such tinnitus to be associated with hyperactivity of a variety of cortical regions, especially the auditory cortices and middle temporal regions. Repetitive transcranial magnetic stimulation (rTMS) involves the application of frequent, repeated magnetic stimuli to the skull to induce electrical activity in the underlying cortical areas of the brain. At low-frequency (1 Hz) stimulation, it is believed that rTMS leads to an increase in the inhibitory activity of glutaminergic fibers in the CNS. rTMS seems to be a novel and promising treatment modality for tinnitus as it may be able to quiet the hyperactive cortical areas recently identified through neuroimaging that contribute to tinnitus. Preliminary research by the investigators included PET scan and rTMS for 6 subjects. Of the 6 subjects, 3 reported a 20-point reduction or greater in the Tinnitus Handicap Inventory (THI). When asked if they would recommend rTMS treatment to a friend, 4 patients responded favorably ("maybe yes" or "definitely yes"). The Overall Goal in this collaborative research project is to assess the effectiveness of rTMS in a large number of tinnitus patients and to thoroughly assess whether there are patient and clinical factors that are predictors of outcome. We will also assess whether there are patient, clinical, neurocognitive, and neuroimaging changes associated with rTMS treatment. There are three Specific Aims to this project: 1) To assess the therapeutic benefit of rTMS for subjective idiopathic troublesome tinnitus. We will employ a single-blind cross-over randomized trial design of active vs. sham rTMS. Enrollment will consist of 55 subjects; the sample size will ensure sufficient power to detect a clinically meaningful difference between treatments, defined as 20-point change in the THI score. A variety of neurocognitive function tests, before and after treatment, will be included to assess whether there are any significant adverse effects of rTMS on cognition and executive function. 2) To identify predictors and correlates of response to rTMS therapy for patients with severe tinnitus. The hypothesis is that there are certain patient factors, audiological measures, clinical features, neurocognitive features, and PET scan findings at baseline and certain changes in these factors after rTMS treatment that are predictors of response to rTMS. 3) To identify a unique tinnitus patient phenotype that is more likely to respond to rTMS The hypothesis is that we will be able to identify certain patient factors, audiological measures, clinical features, and neurocognitive factors that can be used to identify patients more likely to benefit from rTMS. Upon completion of this collaborative research project, new knowledge will be gained about the efficacy of rTMS for tinnitus. This study is unique since all subjects will have thorough neurocognitive testing and PET scan imaging at baseline, after sham, and after active treatment.

描述（由申请人提供）：慢性失能性主观耳鸣对于许多美国人来说是一个严重的问题。神经影像学研究表明，这种耳鸣与多个皮质区域的过度活跃有关，特别是听觉皮质和颞中区。重复经颅磁刺激 (rTMS) 涉及对颅骨施加频繁、重复的磁刺激，以诱导大脑底层皮质区域的电活动。在低频（1 Hz）刺激下，rTMS 被认为会导致中枢神经系统中谷氨酰胺能纤维的抑制活性增加。 rTMS 似乎是一种新颖且有前途的耳鸣治疗方式，因为它可能能够使最近通过神经影像学发现的导致耳鸣的过度活跃的皮质区域安静下来。研究人员的初步研究包括对 6 名受试者进行 PET 扫描和 rTMS。在 6 名受试者中，有 3 名受试者的耳鸣障碍量表 (THI) 降低了 20 分或更多。当被问及是否会向朋友推荐 rTMS 治疗时，4 名患者给出了积极的回应（“也许会”或“肯定会”）。该合作研究项目的总体目标是评估 rTMS 在大量耳鸣患者中的有效性，并彻底评估是否存在可预测结果的患者和临床因素。我们还将评估是否存在与 rTMS 治疗相关的患者、临床、神经认知和神经影像学变化。该项目有三个具体目标： 1) 评估 rTMS 对主观特发性耳鸣的治疗效果。我们将采用主动与假 rTMS 的单盲交叉随机试验设计。招生将包括 55 个科目；样本量将确保有足够的功效来检测治疗之间具有临床意义的差异，定义为 THI 评分的 20 分变化。将包括治疗前后的各种神经认知功能测试，以评估 rTMS 是否对认知和执行功能有任何显着的不利影响。 2) 确定重度耳鸣患者对 rTMS 治疗反应的预测因素和相关因素。假设基线时存在某些患者因素、听力学测量、临床特征、神经认知特征和 PET 扫描结果，以及 rTMS 治疗后这些因素的某些变化是 rTMS 反应的预测因素。 3) 识别更有可能对 rTMS 做出反应的独特耳鸣患者表型 假设我们将能够识别某些患者因素、听力学测量、临床特征和神经认知因素，这些因素可用于识别更有可能对 rTMS 做出反应的患者。从 rTMS 中受益。该合作研究项目完成后，将获得有关 rTMS 治疗耳鸣功效的新知识。这项研究的独特之处在于，所有受试者都将在基线、假手术后和积极治疗后进行彻底的神经认知测试和 PET 扫描成像。