Speech Entrainment for Aphasia Recovery (SpARc)

摘要 尽管最近在急性中风的治疗方面取得了进展，但20%的慢性中风幸存者患有 长期语言障碍（失语症）。非流利性失语症是失语症最常见的形式之一， 它与社会孤立，减少参与康复治疗，以及低 生活质量在治疗过程中，重建流利的语言是最具挑战性的方面之一 慢性非流利性失语症患者的研究。作为这个问题的一个新的替代方案，我们的小组已经优化了一个 一种新的和有前途的治疗方法，名为语音诱导治疗（SET），其中受试者的语音 被膝上型计算机上呈现的视听模型牵拉沿着（引导）。在初步和证明 在概念研究中，我们观察到非流利性失语的受试者可以克服流利性障碍， 用SET产生更流畅的语音。他们每分钟在动词方面的进步超过20% (VPM)在治疗后三个月的自发言语中。这些都是非常令人鼓舞的发现 因为它们代表了在话语过程中产生动词的持续后处理收益，这是一个有效的 与产生名词或命名相比， 对象基于这些发现，我们提出了一个前瞻性对照随机评估或盲态阶段， II临床试验，题为言语诱导失语症恢复（SpARc），以更好地评估语言 与SET相关的改善，并确定SET的最佳剂量。本试验将是一个多站点（5 研究中心）项目，将招募150名患有非流畅性失语症的长期稳定卒中幸存者， 结果将是治疗后3个月的VPM。我们将使用无缝两阶段剂量选择设计， 这将包括选择最佳SET剂量的第1阶段和评估SET的全部效果的第2阶段。在 第1阶段，患者将被随机分配至3种不同剂量的SET：3或4.5或6周，每天1小时SET， 或对照（无治疗）条件（4组中每组20名患者）。根据预定义的规则，我们 将选择表现出足够耐受性且与最高组平均值相关的剂量 治疗后3个月的VPM。在第二阶段，我们将招募70名额外的患者，并以1：1的比例随机分配 选择SET持续时间或控制组。最后的分析将测试是否从变化 使用入组患者的选定SET持续时间组的VPM基线优于对照组 第一阶段和第二阶段。如果SET能改善20%或以上，则认为值得进一步研究。 治疗后3个月的VPM与未治疗对照条件相比。这项研究将提供一个 更好地了解SET的治疗益处，确定其最佳剂量，并决定其效果是否 将证明这种新的和有前途的治疗形式的未来研究。

Abstract In spite of recent advances in the treatment of acute stroke, 20% of chronic stroke survivors suffer from long-lasting language impairments (aphasia). Non-fluent aphasia is one of the most common forms of aphasia, and it is directly associated with social isolation, decreased participation in rehabilitation therapies, and low quality of life. The reestablishment of fluent speech is one of the most challenging aspects during the treatment of subjects with chronic non-fluent aphasia. As a novel alternative to this problem, our group has optimized a new and promising treatment approach entitled speech entrainment therapy (SET), where the subject's speech is pulled along (guided by) an audio-visual model presented on a laptop computer. In a preliminary and proof of concept study, we observed that subjects with non-fluent aphasia could overcome the barrier towards fluency and produce more fluent speech with SET. They had greater than 20% improvement in verbs per minute (VPM) during spontaneous speech at three months after therapy. These are very encouraging findings because they represent sustained post-treatment gains in producing verbs during discourse, which is a valid ecological measure, and a better predictor of language abilities compared with producing nouns or naming objects. Motivated by these findings, we propose a prospective controlled randomized assessor blinded phase II clinical trial entitled Speech entrainment for Aphasia Recovery (SpARc) to better assess the linguistic improvements associated with SET, and to determine the optimal dose of SET. This trial will be a multisite (5 sites) project that will enroll 150 chronically stable stroke survivors with non-fluent aphasia, and the primary outcome will be VPM at 3 months post-therapy. We will use a Seamless Two-Stage Dose Selection design, which will include a Stage 1 to choose the best SET dose, and a Stage 2 to assess the full effects of SET. In Stage 1, the patients will be randomized to 3 different doses of SET: 3 or 4.5 or 6 weeks of 1 hour daily SET, or a control (no treatment) condition (20 patients in each one of the 4 groups). Based on a pre-defined rule, we will select the dose that demonstrated adequate tolerability and was associated the highest group average VPM at 3 months post treatment. In Stage 2, we will enroll 70 additional patients and randomly assign them 1:1 to either the selected SET duration or the control group. The final analysis will test whether the change from baseline in VPM for the selected SET duration group is better than the control group using patients enrolled in Stages 1 and 2. SET will be considered worthy of further study if it leads to an improvement in 20% or more in VPM at 3 months after therapy compared with the no treatment control condition. This study will provide a better understanding of the therapeutic benefits of SET, determine its best dose, and decide whether its effects would justify future studies of this new and promising form of therapy.