Escitalopram and Language Intervention for Subacute Aphasia (ELISA)

艾司西酞普兰和亚急性失语症语言干预 (ELISA)

• 批准号: 10390287
• 负责人: Argye E. Hillis
• 金额: $ 45.02万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10390287
• 关键词: Affect; Aftercare; Alleles; Amphetamines; Anodes; Anxiety; Aphasia; Brain; Brain-Derived Neurotrophic Factor; Clinical Trials; Communication; Computers; Data; Dopamine; Double-Blind Method; Education; Effectiveness; Electronic Mail; Escitalopram; FDA approved; Fluoxetine; Functional Magnetic Resonance Imaging; Genes; Genetic Polymorphism; Genotype; Goals; Hospitals; Hour; Individual; Infarction; Insurance; Interpersonal Relations; Intervention; Language; Language Therapy; Left; Lesion; Light; Literature; Magnetic Resonance Imaging; Measures; Mediating; Medical; Mental Depression; Motor; Names; Outcome; Participant; Persons; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Placebo Control; Placebos; Production; Provider; Quality of life; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recovery; Recovery Support; Rehabilitation therapy; Research; Research Personnel; Residual state; Rest; Risk; Selective Serotonin Reuptake Inhibitor; Severities; Single Nucleotide Polymorphism; Social Interaction; Speech; Stroke; Structure; Superior temporal gyrus; Survivors; Telephone; Testing; Transcranial magnetic stimulation; United States; White Matter Disease; Work; aphasia recovery; base; cognitive recovery; design; disability; double-blind placebo controlled trial; genetic testing; improved; language impairment; meetings; motor recovery; neuromechanism; post stroke; response; secondary outcome; side effect; social; stroke survivor; stroke-induced aphasia; treatment response

Project Summary (Project 2) Aphasia, or language impairment, is among the most devastating problems after left hemisphere stroke, because it can interfere with an individual’s social interactions, ability to return to work, and even simple daily activities, such as returning email or answering the phone. Speech and language treatment (SLT) can be helpful in restoring language function, but recovery is often incomplete. Recent studies indicate that motor and cognitive recovery after stroke can be augmented with selective serotonin reuptake inhibitors (SSRIs). With this proposal, we aim to evaluate the effect of an SSRI, escitalopram, given daily for 3 months after stroke, on augmenting language recovery. We will compare the effects of escitalopram plus SLT to placebo plus SLT in a double blind, randomized controlled trial (RCT). SLT will consist of “standard” language therapy for two months, followed by a daily, computer-delivered naming therapy (CoDeNT) over 15 sessions beginning at two months. We selected this SLT to enable us to compare the effects of escitalopram to the effect of transcranial direct current stimulation (tDCS) versus sham with the same SLT, in our ongoing study of tDCS plus aphasia treatment in subacute stroke. We will evaluate the effect of escitalopram on naming untrained objects (one of the most common deficits in aphasia), and secondarily, its effects on morphosyntactic production, content and efficiency of narrative speech, quality of life, and disability. We will evaluate the influence of treatment and demographic variables, lesion volume, white matter disease, aphasia and stroke severity, and education on outcome. Based on recent studies from the Center for the Study of Aphasia Recovery and from the literature, we will also identify neural mechanisms that may mediate the effects of language recovery with treatment, including the influence of abnormal polymorphisms in the brain derived neurotrophic factor (BDNF) gene. We will also evaluate the effects of escitalopram on “functional connectivity” at rest (or correlations in activation between regions of “the language network” in the brain versus other networks in the brain, such as the motor network), comparing resting state functional connectivity MRI before any intervention and after escitalopram or placebo with SLT. This aim may shed light on the mechanisms of how escitalopram affects language, and/or how language recovers with or without medication, independently on the effects of escitalopram on depression. We will test our hypotheses in a RCT, Escitalopram for Language Improvement in Subacute Aphasia (ELISA). Neither the participant with aphasia nor the investigator will be unmasked until the end of the study. The long- term aim of this study is to provide the basis for a Phase III randomized controlled trial of either escitalopram, anodal-tDCS, or both with concurrent SLT for treatment of subacute aphasia. This study will help us determine which intervention(s) is likely to augment SLT and allow us to select the best candidates for treatment in the larger study.

项目概要（项目2） 失语症或语言障碍是左半球中风后最具破坏性的问题之一 因为它会干扰个人的社交互动、重返工作岗位的能力，甚至简单的日常生活 活动，例如回复电子邮件或接听电话。言语和语言治疗 (SLT) 可以 有助于恢复语言功能，但恢复往往不完全。最近的研究表明，运动和 选择性血清素再摄取抑制剂（SSRI）可以增强中风后的认知恢复。和 在该提案中，我们的目的是评估 SSRI（艾司西酞普兰）在中风后 3 个月内每日服用的效果， 增强语言恢复。我们将比较艾司西酞普兰加 SLT 与安慰剂加 SLT 的效果 双盲、随机对照试验（RCT）。 SLT 将包括针对两个人的“标准”语言治疗 几个月，然后每天进行 15 次计算机提供的命名治疗 (CoDeNT)，从凌晨 2 点开始 几个月。我们选择此 SLT 是为了能够比较艾司西酞普兰和经颅药物的效果 在我们正在进行的 tDCS 联合失语症研究中，直流电刺激 (tDCS) 与使用相同 SLT 的假手术比较 亚急性中风的治疗。我们将评估艾司西酞普兰对命名未经训练的对象（其中之一）的影响 失语症中最常见的缺陷），其次是它对形态句法产生、内容和语言的影响。 叙述性言语的效率、生活质量和残疾。我们将评估治疗的影响并 人口统计学变量、病变体积、白质疾病、失语症和中风严重程度以及相关教育 结果。根据失语症恢复研究中心的最新研究和文献， 我们还将确定可能通过治疗调节语言恢复效果的神经机制， 包括脑源性神经营养因子（BDNF）基因异常多态性的影响。我们 还将评估艾司西酞普兰对休息时“功能连接”的影响（或激活的相关性） 大脑中“语言网络”的区域与大脑中其他网络（例如运动网络）之间的关系 网络），比较任何干预之前和艾司西酞普兰或之后的静息态功能连接 MRI 安慰剂与 SLT。这一目标可能揭示艾司西酞普兰如何影响语言的机制，和/或 无论是否服用药物，语言如何恢复，与艾司西酞普兰对抑郁症的影响无关。 我们将在随机对照试验（艾司西酞普兰用于亚急性失语症语言改善（ELISA））中测试我们的假设。 在研究结束之前，患有失语症的参与者和研究者都不会被揭露。长- 本研究的短期目标是为艾司西酞普兰的 III 期随机对照试验提供基础， 阳极 tDCS 或两者同时进行 SLT 治疗亚急性失语症。这项研究将帮助我们确定 哪些干预措施可能会增强 SLT 并使我们能够选择最佳的治疗候选者 更大的研究。