Effects of octanoic acid for treatment of essential voice tremor

描述（由申请人提供）：原发性震颤是最常见的运动障碍之一，影响近5%的65岁以上的人。由于预计老年人口将不成比例地增长，预计今后10年这种疾病的流行率将增加。特发性震颤的特点是有节奏的，不自主的运动，往往影响上肢，但也可以影响头部，躯干和语音相关的结构。震颤的起源被认为是在小脑和中枢神经系统（CNS）的相关通路内1，2。在特发性嗓音震颤（EVT）中，与嗓音相关的结构的重复运动产生语音信号的调制。感知声音的影响包括增加不稳定性，声音嘶哑和发声努力3，4，这对语音清晰度产生负面影响，并产生大量的心理和身体负担3。目前对EVT的治疗是不充分的，其有效性可变，可能使有限比例的人受益4 -6。酒精可以减少许多受影响的人的震颤，但其治疗作用受到其中毒作用的限制。辛酸（OA）是一种与酒精有关的食品添加剂，可减少肢体特发性震颤，副作用最小7。辛酸可能会直接影响小脑途径，震颤被认为是起源。该项目的目标是确定OA对EVT患者语音特征的影响。这是第一项针对OA声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，在数据收集和分析期间，参与者和实验者对条件均不知情。将通过比较OA和安慰剂条件之间声音的声学、感知和功能方面的评估前后指标的变化来确定结果。具体而言，目标I和II将确定OA对震颤的声学幅度和感知到的语音震颤严重程度的影响。目的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。据推测，OA，它可以影响多个语音相关的肌肉，将产生更大的减少声音震颤的声音，知觉和功能表现比安慰剂条件。目的IV将确定声音震颤的个体差异和特征，以及这些与治疗反应的关系。拟议的项目将大大推进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.