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急性大脑中动脉卒中经颅直流电刺激试验性随机对照试验(STICA)的设计与方法

Design and Methodology of a Pilot Randomized Controlled Trial of Transcranial Direct Current Stimulation in Acute Middle Cerebral Artery Stroke (STICA).

作者信息

Pruvost-Robieux Estelle, Calvet David, Ben Hassen Wagih, Turc Guillaume, Marchi Angela, Mélé Nicolas, Seners Pierre, Oppenheim Catherine, Baron Jean-Claude, Mas Jean-Louis, Gavaret Martine

机构信息

Department of Neurophysiology, Sainte-Anne Hospital, Paris, France.

Faculty of Medicine, Paris Descartes University, Paris, France.

出版信息

Front Neurol. 2018 Oct 9;9:816. doi: 10.3389/fneur.2018.00816. eCollection 2018.

Abstract

Stroke is a major cause of death and disability worldwide. The related burden is expected to further increase due to aging populations, calling for more efficient treatment. Ischemic stroke results from a focal reduction in cerebral blood flow due to the sudden occlusion of a brain artery. Ischemic brain injury results from a sequence of pathophysiological events that evolve over time and space. This cascade includes excitotoxicity and peri-infarct depolarizations (PIDs). Focal impairment of cerebral blood flow restricts the delivery of energetics substrates and impairs ionic gradients. Membrane potential is eventually lost, and neurons depolarize. Although recanalization therapies target the ischemic penumbra, they can only rescue the penumbra still present at the time of reperfusion. A promising novel approach is to "freeze" the penumbra until reperfusion occurs. Transcranial direct current stimulation (tDCS) is a non-invasive method of neuromodulation. Based on preclinical evidence, we propose to test the penumbra freezing concept in a clinical phase IIa trial assessing whether cathodal tDCS-shown in rodents to reduce infarction volume-prevents early infarct growth in human acute Middle Cerebral Artery (MCA) stroke, in adjunction to conventional revascularization methods. This is a monocentric randomized, double-blind, and placebo-controlled trial performed in patients with acute MCA stroke eligible to revascularization procedures. Primary outcome is infarct volume growth on diffusion weighted imaging (DWI) at day 1 relative to baseline. Secondary outcomes include safety and clinical efficacy. Results from this clinical trial are expected to provide rationale for a phase III study. -EUDRACT: 2016-A00160-51.

摘要

中风是全球范围内导致死亡和残疾的主要原因。由于人口老龄化,相关负担预计将进一步增加,这就需要更有效的治疗方法。缺血性中风是由于脑动脉突然闭塞导致脑血流量局部减少所致。缺血性脑损伤是由一系列随时间和空间演变的病理生理事件引起的。这一连串事件包括兴奋性毒性和梗死周围去极化(PIDs)。脑血流量的局部受损限制了能量底物的供应并损害了离子梯度。膜电位最终丧失,神经元去极化。尽管再灌注疗法针对缺血半暗带,但它们只能挽救再灌注时仍存在的半暗带。一种有前景的新方法是在再灌注发生之前“冻结”半暗带。经颅直流电刺激(tDCS)是一种非侵入性神经调节方法。基于临床前证据,我们建议在一项IIa期临床试验中测试半暗带冻结概念,评估在联合传统血管再通方法时,阴极tDCS(在啮齿动物中显示可减少梗死体积)是否能防止人类急性大脑中动脉(MCA)中风的早期梗死扩大。这是一项在符合血管再通程序的急性MCA中风患者中进行的单中心随机、双盲和安慰剂对照试验。主要结局是第1天相对于基线的扩散加权成像(DWI)上的梗死体积增长。次要结局包括安全性和临床疗效。该临床试验的结果有望为III期研究提供理论依据。-欧盟临床试验注册号:2016-A00160-51

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d9f/6190876/82d3dc1346c4/fneur-09-00816-g0001.jpg

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