Safety and efficacy of transcranial direct current stimulation in addition to constraint-induced movement therapy for post-stroke motor recovery (TRANSPORT2): a phase 2, multicentre, randomised, sham-controlled triple-blind trial.

Studies of transcranial direct current stimulation (tDCS), combined with various rehabilitation therapies, have shown promising results in reducing motor impairment.

结合各种康复疗法的经颅直流电刺激（tDCS）研究显示，在减少运动障碍方面取得了令人鼓舞的结果。

We aimed to evaluate the safety and efficacy of three doses of tDCS in combination with modified constraint-induced movement therapy (mCIMT) in people who have had their first ischaemic stroke in the preceding 1-6 months.

我们旨在评估三种剂量的经颅直流电刺激（tDCS）结合改良限制性运动疗法（mCIMT）在1-6个月内首次发生缺血性中风患者中的安全性和有效性。

Methods

We conducted a phase 2, multicentre, randomised, triple-blind, sham-controlled study with a blinded centrally scored primary outcome.

我们进行了一项2期、多中心、随机、三盲、安慰剂对照研究，主要结果由中央盲评。

The trial was conducted at 15 medical centres in the USA.

该试验在美国的15个医疗中心进行。

Eligible participants were enrolled between 1 month and 6 months after their first ischaemic stroke.

符合条件的参与者在首次缺血性中风后的1个月至6个月之间被纳入研究。

Inclusion criteria required participants to have a persistent motor deficit, defined as a Fugl-Meyer Upper-Extremity (FM-UE) score of 54 or lower (out of 66), and two consecutive baseline visits (separated by 7-14 days) with an absolute difference of 2 or fewer points on the FM-UE scale.

纳入标准要求参与者有持续的运动功能障碍，定义为Fugl-Meyer上肢（FM-UE）评分54分或以下（满分66分），以及两个连续的基线访问（相隔7-14天），在FM-UE量表上的绝对差值为2分或更少。

Participants were randomly assigned to treatment groups by an adaptive randomisation algorithm hosted on the TRANSPORT2 WebDCU study website.

参与者通过TRANSPORT2 WebDCU研究网站上托管的自适应随机化算法随机分配到治疗组。

Participants received either sham, 2 mA, or 4 mA of bi-hemispheric tDCS for the first 30 min and mCIMT with 120 min of active therapy time per session, administered over ten sessions during a 2-week period.

参与者接受了假刺激、2毫安或4毫安的双半球经颅直流电刺激（tDCS）的前30分钟，以及每次会话120分钟的活动性运动和感觉综合疗法（mCIMT），在两周内共进行十次会话。

The primary endpoint was the change in FM-UE score from baseline to day 15, which was analysed in all participants who have data both at baseline and post-baseline (modified intention-to-treatgroup).

主要终点是基线至第15天FM-UE评分的变化，分析了所有在基线和基线后都有数据的参与者（修改意向治疗组）。

Safety outcomes were analysed in all participants.

所有参与者的安全性结果都进行了分析。

TRANSPORT2 is registered at clinicaltrials.gov (NCT03826030) and its status is completed.

TRANSPORT2已在clinicaltrials.gov上注册（NCT03826030），其状态已完成。

Results

129 participants were recruited between Sept 9, 2019, and June 14, 2024, and 43 participants were randomly assigned to each group. 54 (42%) of 129 participants were female, and 69 (53%) were White.

在2019年9月9日至2024年6月14日期间，共招募了129名参与者，其中每组随机分配了43名参与者。在129名参与者中，54名（占42%）为女性，69名（占53%）为白人。

Two participants in the sham plus mCIMT group withdrew consent before the day 15 assessment and were excluded from the primary analysis.

在安慰剂加改良强制性运动疗法（mCIMT）组中，有两名参与者在第15天评估前撤回了同意，因此被排除在主要分析之外。

The median baseline FM-UE score was 39·0 (IQR 30·0-46·0) in the sham plus mCIMT group, 39·0 (27·0-48·0) in the 2 mA plus mCIMT group, and 40·0 (27·0-48·0) in the 4 mA plus mCIMT group.

在假治疗加改良强制性运动疗法（mCIMT）组中，基线FM-UE评分的中位数为39·0（四分位数间距IQR 30·0-46·0），在2毫安加mCIMT组中为39·0（27·0-48·0），在4毫安加mCIMT组中为40·0（27·0-48·0）。

For the primary outcome, the adjusted mean change from baseline to day 15 in FM-UE was 4·91 (3·00-6·82) for sham plus mCIMT, 3·87 (2·00-5·74) for 2 mA plus mCIMT, and 5·53 (3·64-7·42) for 4 mA plus mCIMT (p=0·39).

对于主要结果，从基线到第15天FM-UE的调整后平均变化值为：假治疗加mCIMT组为4·91（95%置信区间3·00-6·82），2毫安加mCIMT组为3·87（2·00-5·74），4毫安加mCIMT组为5·53（3·64-7·42）（p=0·39）。

No clinically important adverse events were observed in any group and no deaths were reported.

在任何组中都未观察到任何重要的不良事件，也没有报告死亡。

interpretation

tDCS at doses of 2 mA or 4 mA, in addition to mCIMT, did not lead to further reduction in motor impairment in patients 1-6 months after stroke, but it was safe, well tolerated, and feasible for clinical practice. tDCS at higher doses (ie, >4 mA) might be a consideration for future trials in addition to balancing known covariates affecting stroke recovery during the group allocation.

在2毫安或4毫安剂量的tDCS（经颅直流电刺激）与mCIMT（改良的强制性运动疗法）结合使用时，并没有进一步减少患者在中风后1-6个月的运动障碍，但它是安全的、耐受性好的，并且在临床实践中是可行的。对于更高剂量的tDCS（即，>4毫安）可能会在未来的试验中进行考虑，同时在分组分配时平衡已知影响中风恢复的协变量。

funding

National Institute of Neurological Disorders and Stroke.

国家神经疾病和中风研究所