Clinical Trial of Transcranial Magnetic Stimulation for Relief of Tinnitus

描述（由申请人提供）： 重复经颅磁刺激（rTMS）是一种非侵入性干预，涉及通过线圈向受试者的头皮提供电磁脉冲。最终，这些能量中的一部分通过头骨传输，并影响底层神经组织的活动。由于耳鸣与中枢听觉系统中多余的神经活动有关，因此rTMS有可能降低患者对耳鸣的感知和严重程度。一些研究者已经成功地将rTMS用于相对较少的耳鸣患者人群。目的：我们的长期目标是开发一种安全，实用，有效和成本效益的治疗慢性耳鸣。本提案的目的是实现我们的长期目标的下一步，是在耳鸣患者的大样本中进行设计良好的rTMS安慰剂对照临床试验。这项研究的中心假设是，rTMS可以减少耳鸣的感知时间延长，副作用最小。我们的假设是在支持性初步研究的基础上提出的。具体目标：我们将通过追求以下两个具体目标来测试我们的中心假设并实现本申请的目标：1.在经历慢性耳鸣的大样本人群中进行低频（1 Hz）重复经颅磁刺激（rTMS）的双盲、随机、安慰剂对照临床试验。我们假设，连续10个工作日每天应用2000个1 Hz rTMS脉冲，与安慰剂组相比，治疗组的耳鸣响度和严重程度将在统计学和临床上显著降低。 2.跟踪参加临床试验的受试者治疗后6个月的进展。我们假设治疗组耳鸣响度和严重程度的改善将在随访期间持续。在随访期间，安慰剂组的耳鸣响度和严重程度不会发生显著变化。研究设计：这将是一项前瞻性、随机、受试者和临床医生/观察者盲法、安慰剂对照的rTMS平行组临床试验，涉及168名耳鸣患者的样本。受试者将在连续10个工作日接受活性药物或安慰剂rTMS治疗。将在治疗开始前、每次治疗之前和之后立即测量结局。将在末次治疗后1、2、4、13和26周进行随访评价。这项调查的目标人群（研究结果将被推广到他们）包括那些经历过令人烦恼的慢性耳鸣的人。影响：在研究结束时，将确定和开发最大限度地提高rTMS降低耳鸣严重程度的疗效的方案。然后，临床医生将能够以最有效的方式对耳鸣患者进行rTMS治疗，以降低其病情的严重程度。 公共卫生相关性： 项目叙述：耳鸣（耳朵或头部听到铃声或其他幻听）是所有退伍军人中第二常见的与服务有关的残疾（仅次于听力损失），每年的赔偿总额超过5亿美元。由于慢性耳鸣是一种对全球数百万人的生活质量产生负面影响的疾病，包括美国退伍军人和军事人员，几十年来一直在寻求安全有效的耳鸣治疗方法。耳鸣的病因有哪些？耳鸣的病因有哪些？拟议的临床试验将评估重复经颅磁刺激（rTMS）减少患者耳鸣感知和严重程度的疗效。在整个VA和美国武装部队医疗保健系统中使用这种治疗将提高退伍军人和军事人员的生活质量。在美国各地的医疗诊所实施rTMS治疗将有助于减少经历，治疗和获得令人烦恼的耳鸣补偿的人数。

DESCRIPTION (provided by applicant): Project Summary/Abstract Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive intervention that involves delivering electromagnetic pulses through a coil to the subject's scalp. Ultimately, some of this energy is transmitted through the skull and affects the activity of underlying neural tissue. Because tinnitus is associated with superfluous neural activity in the central auditory system, rTMS has the potential to reduce patients' perception and severity of tinnitus. Several investigators have used rTMS successfully on relatively small populations of tinnitus patients. Objective: Our long-range goal is to develop a safe, practical, effective and cost-effective treatment for chronic tinnitus. The objective of this proposal, the next step toward attaining our long-range goal, is to conduct a well-designed, placebo-controlled clinical trial of rTMS in a large sample of tinnitus sufferers. The central hypothesis of the proposed research is that rTMS can reduce the perception of tinnitus for prolonged periods of time with minimal adverse side effects. Our hypothesis has been formulated on the basis of supportive preliminary studies. Specific Aims: We will test our central hypothesis and accomplish the objective of this application by pursuing the following two specific aims: 1. Conduct a double-blinded, randomized, placebo-controlled clinical trial of low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) in a large sample of people who experience chronic tinnitus. We hypothesize that application of 2000 pulses of 1 Hz rTMS daily for 10 successive work days will result in statistically and clinically significant reductions in tinnitus loudness and severity for the treatment group compared to the placebo group. 2. Track the progress of subjects who participated in the clinical trial for six months post- treatment. We hypothesize that improvements in tinnitus loudness and severity experienced by the treatment group will be sustained during the follow-up period. The placebo group will not experience significant changes in tinnitus loudness and severity during the follow-up period. Study Design: This will be a prospective, randomized, subject and clinician/observer blind, placebo- controlled parallel-group clinical trial of rTMS involving a sample of 168 people who experience tinnitus. Subjects will receive either active or placebo rTMS therapy on 10 consecutive work days. Outcomes will be measured prior to the start of treatment, immediately before and after each therapeutic session. Follow- up evaluations will be conducted 1, 2, 4, 13 and 26 weeks after the last treatment session. The target population (to whom the study findings will be generalized) for this investigation includes people who experience bothersome, chronic tinnitus. Impact: At the conclusion of the study, protocols will be identified and developed that maximize the efficacy of rTMS to reduce tinnitus severity. Clinicians will then be able to administer rTMS therapy to tinnitus patients in the most effective ways to reduce the severity of their condition. PUBLIC HEALTH RELEVANCE: Project Narrative: Tinnitus (the perception of ringing or other phantom sounds in the ears or head) is the second most prevalent service-connected disability (after hearing loss) for all Veterans and results in compensation payments totaling more than $500 million per year. Because chronic tinnitus is a condition that negatively impacts the quality of life for millions of people worldwide, including U.S. Veterans and military personnel, a safe and effective treatment for tinnitus has been sought for decades. However, a true "cure" for the most common etiologies of tinnitus remains elusive. The proposed clinical trial will assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing patients' perception and severity of tinnitus. Utilization of this treatment throughout the VA and U.S. Armed Forces health care systems will improve the quality of life for Veterans and military personnel. Implementation of rTMS therapy in medical clinics across the United States will help to reduce the number of people who experience, are treated for, and receive compensation for bothersome tinnitus.