Effects of octanoic acid for treatment of essential voice tremor

描述（由申请人提供）：特发性震颤是最常见的运动障碍之一，影响了近5%的65岁以上人群。由于预计老年人口将不成比例地增长，预计今后10年这种疾病的患病率将增加。特发性震颤的特点是有节奏的、不自主的运动，通常影响上肢，但也可能影响头部、躯干和与声音有关的结构。震颤的起源被认为是在小脑和中枢神经系统（CNS）的相关途径1,2。在原发性声音震颤（EVT）中，语音相关结构的重复运动产生语音信号的调制。感知性声音效应包括不稳定、声音嘶哑和发声力度增加3,4，这些都会对语音清晰度产生负面影响，并产生巨大的心理和生理负担。目前EVT的治疗不充分，疗效不一，可能使有限比例的人受益4-6。酒精可以减轻许多患者的震颤症状，但由于其令人陶醉的效果，酒精在治疗中的作用有限。辛酸（OA）是一种与酒精有关的食品添加剂，可以减少四肢的原发性震颤，而且副作用最小。辛酸可能直接影响被认为是震颤起源的小脑通路。拟议项目的目标是确定OA对EVT患者语音特征的影响。这是首个针对OA语音特异性影响的研究，代表了推进EVT循证治疗的创新一步。在随机、安慰剂对照的交叉设计中，22名参与者将分别接受OA和安慰剂条件，在数据收集和分析过程中，参与者和实验者都对条件不知情。结果将通过比较OA和安慰剂条件下声音声学、感知和功能方面评估前和评估后的变化来确定。具体而言，Aims I和II将确定OA对震颤的声学强度和感知的声音震颤严重程度的影响。Aim III将确定OA对生活质量和与家人或朋友沟通能力的功能影响。假设OA可以影响多个语言相关肌肉，与安慰剂相比，OA会使声音震颤的声学、感知和功能表现更大的减少。目的IV将确定声音震颤的个体变异性和特征，以及这些与治疗反应的关系。拟议的项目将显著推进EVT临床治疗的循证决策，为减少这种疾病的衰弱效应迈出重要一步。

DESCRIPTION (provided by applicant): Essential tremor is among the most common movement disorders, affecting nearly 5% of people over the age of 65. Increased prevalence of this disorder is expected in the next 10 years due to the projected disproportionate growth of the older population. Essential tremor is characterized by rhythmic, involuntary movements that often affect the upper limbs but can also affect the head, trunk and voice-related structures. The origin of the tremor is thought to be within the cerebellum and related pathways of the central nervous system (CNS)1, 2. In essential voice tremor (EVT), repetitive movements of voice-related structures produce modulations of the speech signal. Perceptual voice effects include increased instability, hoarseness, and vocal effort3, 4, which negatively impact speech intelligibility and produce substantial psychosocial and physical burden3. Current treatment for EVT is inadequate, with variable effectiveness that may benefit a limited proportion of people4-6. Alcohol reduces tremor in many affected people, but its usefulness for treatment is limited by its intoxicating effects. Octanoic acid (OA) is a food additive that is related to alcohol, and produces a reduction in essential tremor of the limbs with minimal side effects7. Octanoic acid may directly affect the cerebellar pathways where tremor is thought to originate. The goal of the proposed project is to determine the effects of OA on the voice characteristics of people with EVT. This represents an innovative step toward advancing the evidence-based treatment of EVT by being the first study to address the voice-specific effects of OA. In a randomized, placebo controlled cross-over design, 22 participants will each receive the OA and placebo conditions, with both participants and experimenters blinded to condition during data collection and analysis. Outcomes will be determined by comparing changes in pre- to post-assessment measures of acoustic, perceptual and functional aspects of voice between the OA and placebo conditions. Specifically, Aims I and II will determine the effects of OA on the acoustic magnitude of tremor and perceived voice tremor severity. Aim III will determine the functional impact of OA on quality of life and ability to communicate with family or friends. It is hypothesized that OA, which can affect multiple speech-related muscles, will produce a greater reduction in acoustic, perceptual and functional manifestations of voice tremor than the placebo condition. Aim IV will determine the individual variability and characteristics of voice tremor, and how these relate to treatment response. The proposed project will significantly advance evidence-based decisions for the clinical treatment of EVT, providing a vital step toward reducing the debilitating effects f this disorder.