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

用于中风后运动恢复的经颅直流电刺激 - II 期研究 (TRANSPORT 2)

• 批准号: 9986172
• 负责人: Wuwei Feng
• 金额: $ 187.26万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9986172
• 关键词: Address; Adverse event; Affect; Anodes; Area; Biological Markers; Brain; Cathodes; Complication; Corticospinal Tracts; Data; Devices; Dose; Future; Hand; Injury; Innovative Therapy; Intervention; Lesion; Literature; Measures; Meta-Analysis; Modality; Monitor; Motor; Motor Activity; Motor Evoked Potentials; Motor Pathways; Motor Skills; Neuronal Plasticity; Outcome; Outcome Measure; Patient Selection; Peripheral; Phase; Phase II Clinical Trials; Process; Protocols documentation; Public Health; Publishing; Quality of life; Randomized; Recovery; Rehabilitation therapy; Research; Research Design; Research Personnel; Safety; Selection Criteria; Signal Transduction; Site; Standardization; Stroke; Structure; Subjects Selections; Synapses; Synaptic plasticity; Techniques; Testing; Time; Treatment Protocols; Upper Extremity; Visual; Wolves; adjudication; analog; arm; axonal sprouting; base; clinically significant; constraint induced movement therapy; density; design; disability; dosage; functional improvement; motor deficit; motor function recovery; motor impairment; motor recovery; motor rehabilitation; multi-site trial; myelination; patient biomarkers; phase 1 study; phase 2 study; phase 3 study; phase III trial; post intervention; post stroke; response; secondary outcome; skill acquisition; stroke patient; stroke survivor; tool; treatment effect

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.

中风是导致残疾的主要原因，运动障碍是中风后最常见的并发症。 卒中后运动功能的恢复主要归因于结构和/或功能 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，包括揭开先前存在的连接，建立新的突触 通过轴突萌发、皮损周围和相应对侧区域的重组进行联系； 卒中引起的大脑半球间异常相互作用的调制。 经颅直流电刺激(Tdcs)，一种非侵入性的脑刺激技术，已被证明 促进和增强大脑可塑性，调节兴奋性和抑制性半球间失衡 这是在中风后发展起来的。当结合外周康复治疗时，tdcs可以增强 突触可塑性和运动技能的获得/巩固通过增加或调节传入到 大脑皮层同时接受中枢刺激。此外，荟萃分析表明， 电流密度与运动损伤减轻之间的剂量-反应关系。最近出版的一本书 目前的I期升级研究表明，对于中风患者来说，高达4 mA是安全和可耐受的。这是一个 在继续监测安全性和耐受性问题的同时，进行剂量选择第二阶段研究的合乎逻辑的步骤。 改良CIMT(MCIMT)是一种外围疗法，克服了中风患者习得的不使用现象。 该协议是有效的、标准化的和可量化的。 这项建议的主要目的是确定三者之间是否有总体治疗效果 干预2周后立即给药组(假手术+mCIMT、2 mA+mCIMT和4 mA+mCIMT) Fugl-Myer上肢评分(一种运动障碍的衡量标准)。其他成果衡量标准包括 Wolf运动功能测试时间评分(衡量功能运动活动的指标)和卒中影响量表 手工分量表(衡量生活质量的一个指标)。持续收益的评估期限为1个月和3个月 干预后几个月。次级目标将评估实施这一目标的安全性、耐受性和可行性 多点试验中的组合方法。一个探索性的目标将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性评估)或运动诱发电位 (MEP，下行运动束完整性的功能评估)或两者的组合是相关的 随着FM-UE量表的变化，并评估这些测量作为患者选择的生物标志物的有效性 在未来的验证性第三阶段研究中的标准。