高清阴极直流电刺激治疗急性缺血性脑卒中的随机临床试验。

High-definition Cathodal Direct Current Stimulation for Treatment of Acute Ischemic Stroke: A Randomized Clinical Trial.

机构信息

Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine at UCLA, Los Angeles, California.

Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, California.

出版信息

JAMA Netw Open. 2023 Jun 1;6(6):e2319231. doi: 10.1001/jamanetworkopen.2023.19231.

DOI:10.1001/jamanetworkopen.2023.19231

PMID:37342040

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10285579/

Abstract

IMPORTANCE

Cathodal transcranial direct current stimulation (C-tDCS) provides neuroprotection in preclinical models of acute ischemic stroke (AIS) by inhibiting peri-infarct excitotoxic effects and enhancing collateral perfusion due to its vasodilatory properties.

OBJECTIVE

To report the first-in-human pilot study using individualized high-definition (HD) C-tDCS as a treatment of AIS.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was sham controlled with 3 + 3 dose escalation design, and was conducted at a single center from October 2018 to July 2021. Eligible participants were treated for AIS within 24 hours from onset, had imaging evidence of cortical ischemia with salvageable penumbra, and were ineligible for reperfusion therapies. HD C-tDCS electrode montage was selected for each patient to deliver the electric current to the ischemic region only. Patients were followed for 90 days.

MAIN OUTCOMES AND MEASURES

Primary outcomes were feasibility, assessed as time from randomization to study stimulation initiation; tolerability, assessed by rate of patients completing the full study stimulation period; and safety, assessed by rates of symptomatic intracranial hemorrhage at 24 hours. The efficacy imaging biomarkers of neuroprotection and collateral enhancement were explored.

RESULTS

A total of 10 patients with AIS were enrolled, 7 were randomized to active treatment and 3 to sham. Patient age was mean (SD) 75 (10) years old, 6 (60%) were female, and National Institutes of Health Stroke Scale score was mean (SD) 8 (7). Two doses of HD C-tDCS (1 milliamp [mA] for 20 minutes and 2 mA for 20 minutes) were studied. The speed of HD C-tDCS implementation was a median (IQR) 12.5 minutes (9-15 minutes) in the last 4 patients. Patients tolerated the HD C-tDCS with no permanent stimulation cessation. The hypoperfused region was reduced by a median (IQR) 100% (46% to 100%) in the active group vs increased by 325% (112% to 412%) in sham. Change in quantitative relative cerebral blood volume early poststimulation was a median (IQR) 64% (40% to 110%) in active vs -4% (-7% to 1%) sham patients and followed a dose-response pattern. Penumbral salvage in the active C-tDCS group was median (IQR) 66% (29% to 80.5%) vs 0% (IQR 0% to 0%) in sham.

CONCLUSION AND RELEVANCE

In this randomized, first-in-human clinical trial, HD C-tDCS was started efficiently and well tolerated in emergency settings, with signals of beneficial effect upon penumbral salvage. These results support advancing HD C-tDCS to larger trials.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT03574038.

摘要

重要性

经颅直流电刺激（tDCS）通过抑制梗死周围的兴奋性毒性作用并增强侧支灌注（由于其血管扩张特性），在急性缺血性中风（AIS）的临床前模型中提供神经保护作用。

目的

报告首例使用个体化高清（HD）tDCS 作为 AIS 治疗的人体初步研究。

设计、地点和参与者：这是一项单中心、随机临床试验，采用假对照和 3+3 剂量递增设计，于 2018 年 10 月至 2021 年 7 月进行。入选患者在发病后 24 小时内接受 AIS 治疗，有皮质缺血的影像学证据且有可挽救的半影区，不符合再灌注治疗条件。为每位患者选择 HD tDCS 电极放置方式，以将电流仅输送至缺血区域。患者接受 90 天随访。

主要结果和措施

主要结果为时间，从随机分组到研究刺激开始的时间；完成全研究刺激周期的患者比例（可评估为患者对治疗的耐受性）；24 小时内症状性颅内出血的发生率（可评估为治疗的安全性）。探索了神经保护和侧支增强的疗效影像学生物标志物。

结果

共纳入 10 例 AIS 患者，7 例随机分配至活性治疗组，3 例分配至假刺激组。患者年龄为平均（标准差）75（10）岁，6 例（60%）为女性，美国国立卫生研究院中风量表评分为平均（标准差）8（7）分。研究了两种剂量的 HD tDCS（1 mA 持续 20 分钟和 2 mA 持续 20 分钟）。在最后 4 例患者中，HD tDCS 的实施速度中位数（IQR）为 12.5 分钟（9-15 分钟）。患者耐受 HD tDCS，无永久性刺激停止。与假刺激组相比，活性组的低灌注区域减少了中位数（IQR）100%（46%至 100%），而假刺激组增加了中位数（IQR）325%（112%至 412%）。刺激后早期定量相对脑血容量的变化在活性组中中位数（IQR）为 64%（40%至 110%），而假刺激组为中位数（IQR）-4%（-7%至 1%），呈现出剂量反应模式。活性 C-tDCS 组的半影区抢救中位数（IQR）为 66%（29%至 80.5%），而假刺激组为 0%（IQR 0%至 0%）。