Trans-cranial Direct Current Stimulation to Treat Aphasia: Phase II Trial

描述（由申请人提供）：中风是美国成人残疾的主要原因。中风导致的最具破坏性的损伤之一是失语症，这是一种由涉及皮质语言区的左半球损伤引起的语言损伤。虽然大量的研究工作集中在提高失语症的治疗效果，大多数慢性中风失语症患者的经验有限的恢复。因此，提高失语症的治疗效果是最重要的利益，因为它可以提高患者的沟通能力和生活质量。最近利用动物模型的研究表明，低电流经颅直流电刺激（tDCS）可以局部增加脑源性神经营养因子（BDNF）的分泌，这是一种对诱导脑可塑性至关重要的蛋白质。人体研究进一步证明了阳极tDCS（A-tDCS）对正常受试者学习的积极作用。这是第一次，我们在一对研究中显示了A-tDCS如何显着增强慢性卒中诱导的失语症患者的命名障碍（命名常见物体的能力受损）的行为治疗效果。利用这些发现以及我们旨在了解与失语症治疗相关的大脑可塑性的其他研究，我们建议进行II期临床试验，以检查A-tDCS对慢性卒中患者的命名障碍治疗结果的影响。该项目将包括一项随机、前瞻性、双盲试验，分为两组（活性组与对照组），其中慢性稳定型卒中患者将接受行为失语症治疗联合A-tDCS或假tDCS（S-tDCS）。由于命名障碍是失语症的标志性损害，并且存在于所有失语症患者中，无论严重程度或失语症类型如何，主要结局因素将是命名障碍的严重程度，定义为正确命名常见物体的能力。这项研究的长期目标是进行III期试验，以确定A-tDCS是否能显著增强行为失语症治疗的效果。如果A-tDCS被证明对失语症治疗结果有积极影响，那么目前接受有限或无治疗获益的患者在与A-tDCS联合治疗时可能会对治疗产生反应。同样，A-tDCS可能会进一步提高在没有直接脑刺激的情况下对治疗有积极反应的患者的治疗效果。

DESCRIPTION (provided by applicant): Stroke is the leading cause of adult disability in the United States. One of the most devastating impairments resulting from stroke is aphasia, a language impairment caused by left hemisphere damage involving cortical language areas. Although considerable research effort has focused on increasing aphasia treatment efficacy, most chronic stroke patients with aphasia experience limited recovery. Therefore, enhanced aphasia treatment outcome is of paramount interest as it may improve patients' communication ability and quality of life. Recent studies utilizing animal models suggest that low current transcranial direct current stimulation (tDCS) can locally increase the secretion of brain derived neurotrophic factor (BDNF), a protein that is crucial for induction of brain plasticity. Research i humans has further demonstrated the positive effect of anodal tDCS (A-tDCS) on learning in normal subjects. For the first time, we have shown in a pair of studies how A-tDCS can significantly enhance the effect of the behavioral treatment of anomia (impaired ability to name common objects) in patients with chronic stroke-induced aphasia. Capitalizing on these findings as well as our other research aimed at understanding brain plasticity associated with aphasia treatment, we propose to conduct a Phase II clinical trial to examine the effect of A-tDCS on anomia treatment outcome in patients with chronic stroke. This project will include a randomized, prospective, double-blind trial with two arms (active vs. control) wherein chronically stable stroke patients will receive behavioral aphasia treatment coupled with either A-tDCS or sham tDCS (S-tDCS). Because anomia is the hallmark impairment in aphasia and is present in all aphasic patients, regardless of severity or aphasia type, the primary outcome factor will be anomia severity, defined as the ability to correctly name common objects. The long-term goal of this research is to conduct a Phase III trial to determine if A-tDCS significantly enhances the effect of behavioral aphasia treatment. If the A-tDCS is proven to have a positive effect on aphasia treatment outcome, it is possible that patients who currently receive limited or no treatment benefit may respond to treatment when it is coupled with A-tDCS. Similarly, it is possible that A-tDCS may further boost the treatment effect for patients who respond positively to treatment in the absence of direct brain stimulation.