TRANScranial direct current stimulation for POst-stroke motor Recover - a phase II sTudy (TRANSPORT 2)

脑卒中是导致残疾的主要原因，运动功能障碍是脑卒中后最常见的并发症。 中风后运动功能的恢复主要归因于结构性和/或功能性损害。 下行运动通路的损伤程度此外，各种形式的神经可塑性也有助于 恢复过程，包括揭露先前存在的连接，建立新的突触， 通过轴突发芽、损伤周围和同源对侧损伤区域的重组进行接触，以及 调节中风引起的异常半球间的相互作用。 经颅直流电刺激（tDCS）是一种非侵入性脑刺激技术，已被证明可以 促进和增强大脑可塑性，调节兴奋性和抑制性半球间失衡 是中风后形成的当与外周康复治疗相结合时，tDCS可以增强 突触可塑性和运动技能获得/巩固通过增加或调节传入输入到 同时接受中枢刺激。此外，荟萃分析表明， 电流密度和运动损伤减少之间的剂量-反应关系。最近发表的一 I期电流递增研究表明，高达4 mA的电流对于中风患者是安全和可耐受的。这是一个 进行剂量选择II期研究的逻辑步骤，同时继续监测安全性和耐受性问题。 改良CIMT（mCIMT）是一种外周治疗，克服了卒中患者的习得性不使用现象。 该方案是有效的、标准化的和可量化的。 本提案的主要目的是确定三者之间是否存在整体治疗效果 给药组（假手术+mCIMT，2 mA+mCIMT和4 mA+mCIMT）在2周干预后立即在 Fugl-Myer上肢功能量表（运动障碍的测量）。其他结果指标包括 Wolf运动功能测试时间评分（功能性运动活动的测量）和卒中影响量表 手分量表（生活质量的衡量标准）。持续效益在1个月以及3个月时评估 干预后几个月。次要目的将评估安全性、耐受性和实施该方案的可行性 多中心试验中的联合方法。一个探索性的目标是检查加权的皮质脊髓束- 损伤负荷（wCST-LL，下行运动束完整性的结构评估）或运动诱发电位 (MEPs下行运动束完整性的功能评估）或两者的组合是相关的 FM-UE量表的变化，并评估这些指标作为患者选择生物标志物的效用 在未来的验证性III期研究中的标准。

Stroke is a leading cause of disability, with motor deficit as the most common complication after stroke. Recovery of motor function after a stroke has been primarily attributed to the structural and/or functional degree of injury to the descending motor pathways. In addition, various forms of neuroplasticity also contribute to the recovery process, including unmasking of pre-existing connections, the establishment of new synaptic contacts through axonal sprouting, reorganization of peri-lesional and homologous contralesional regions, and modulation of stroke-induced abnormal interhemispheric interactions. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, has been shown to promote and enhance brain plasticity and to modulate the excitatory and inhibitory interhemispheric imbalance that developed after a stroke. When combined with a peripheral rehabilitation therapy, tDCS can enhance synaptic plasticity and motor skill acquisition/consolidation by increasing or modulating afferent inputs to the cortex while concurrently receiving central stimulation. Furthermore, meta-analyses have demonstrated a dose-response relationship between current density and motor impairment reduction. A recently published phase I current escalation study has shown that up to 4mA is safe and tolerable for stroke patients. It is a logical step to conduct a dose selection phase II study while continuing to monitor safety and tolerability issue. Modified CIMT(mCIMT), a peripheral therapy, overcomes a learned non-use phenomenon in stroke patients. The protocol is effective, standardized and quantifiable. The primary aim of this proposal is to determine whether there is an overall treatment effect among the three dosing groups (sham+mCIMT, 2 mA+mCIMT and 4 mA+mCIMT) immediately after 2-week intervention in the Fugl-Myer Upper-Extremity Scale (a measure of motor impairment). Additional outcome measures include the Wolf Motor Function Test Time Score (a measure of functional motor activity), and the Stroke Impact Scale Hand Subscale (a measure of the quality of life). The sustained benefit is assessed at 1 month as well as 3 months post-intervention. Secondary aims will assess safety, tolerability, and feasibility to implement this combined approach in a multi-site trial. An exploratory aim will examine whether weighted corticospinal tract- lesion load (wCST-LL, structural assessment of integrity of descending motor tract) or Motor Evoked Potentials (MEPs, functional assessment of integrity of descending motor tract) or a combination of both are correlated with changes in FM-UE scale, and evaluate the utility of these measures as biomarkers for patient selection criteria in future confirmatory Phase III study.