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

Gottfried Schlaug, Christy Cassarly, Jody A Feld, Steve L Wolf, Veronica T Rowe, Stacy Fritz, Pratik Y Chhatbar, Anant Shinde, Zemin Su, Joseph P Broderick, Richard Zorowitz, Oluwole Awosika, Dylan Edwards, Chen Lin, Gerard E Franciso, George F Wittenberg, Svetlana Pundik, Christopher Gregory, Michael R Borich, Viswanathan Ramakrishnan, Wuwei Feng
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Abstract

Background

Motor impairments contribute substantially to long-term disability following stroke. Studies of transcranial direct current stimulation (tDCS), combined with various rehabilitation therapies, have shown promising results in reducing motor impairment. 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.

Methods

We conducted a phase 2, multicentre, randomised, triple-blind, sham-controlled study with a blinded centrally scored primary outcome. The trial was conducted at 15 medical centres in the USA. Eligible participants were enrolled between 1 month and 6 months after their first ischaemic stroke. 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. Participants were randomly assigned to treatment groups by an adaptive randomisation algorithm hosted on the TRANSPORT2 WebDCU study website. 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. 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-treat group). Safety outcomes were analysed in all participants. TRANSPORT2 is registered at clinicaltrials.gov (NCT03826030) and its status is completed.

Findings

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. Two participants in the sham plus mCIMT group withdrew consent before the day 15 assessment and were excluded from the primary analysis. 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. 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). No clinically important adverse events were observed in any group and no deaths were reported.

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.

Funding

National Institute of Neurological Disorders and Stroke.
经颅直流电刺激和约束诱导运动疗法对脑卒中后运动恢复(TRANSPORT2)的安全性和有效性:一项2期、多中心、随机、假对照三盲试验
运动障碍是中风后长期残疾的主要原因。经颅直流电刺激(tDCS)与各种康复治疗相结合的研究已经显示出减轻运动损伤的良好结果。我们的目的是评估三种剂量的tDCS联合改良约束诱导运动疗法(mCIMT)在前1-6个月内首次缺血性卒中患者中的安全性和有效性。方法:我们进行了一项2期、多中心、随机、三盲、假对照研究,主要结局为盲法中心评分。这项试验在美国的15个医疗中心进行。符合条件的参与者在他们第一次缺血性中风后1到6个月之间入组。纳入标准要求参与者有持续性运动缺陷,定义为Fugl-Meyer上肢(FM-UE)评分为54分或更低(66分),并且连续两次基线就诊(间隔7-14天),FM-UE量表的绝对差值为2分或更少。参与者通过TRANSPORT2 WebDCU研究网站上的自适应随机化算法随机分配到治疗组。参与者在前30分钟接受假,2 mA或4 mA的双半球tDCS和mCIMT,每次120分钟的积极治疗时间,在2周的时间内进行10次治疗。主要终点是FM-UE评分从基线到第15天的变化,对所有具有基线和基线后数据的参与者(修改意向治疗组)进行分析。对所有参与者的安全结果进行分析。TRANSPORT2已在clinicaltrials.gov注册(NCT03826030),其状态已完成。研究人员在2019年9月9日至2024年6月14日期间招募了129名参与者,每组随机分配了43名参与者。129名参与者中有54名(42%)是女性,69名(53%)是白人。sham + mCIMT组的两名参与者在第15天评估前撤回了同意,并被排除在主要分析之外。假手术+ mCIMT组FM-UE评分的中位基线值为39.0 (IQR为30.0 ~ 46.0),2 mA + mCIMT组为39.0 (27.0 ~ 48.0),4 mA + mCIMT组为40.0(27.0 ~ 48.0)。对于主要结局,FM-UE从基线到第15天的调整平均变化,假手术加mCIMT组为4.91 (3.00 - 6.82),2 mA加mCIMT组为3.87 (2.00 - 5.74),4 mA加mCIMT组为5.53 (3.64 - 7.42)(p= 0.39)。在任何组中均未观察到临床上重要的不良事件,无死亡报告。结论:除了mCIMT外,2 mA或4 mA剂量的dcs并没有导致中风后1-6个月患者运动损伤的进一步减少,但它是安全的,耐受性良好,并且在临床实践中是可行的。除了在组分配过程中平衡影响中风恢复的已知协变量外,更高剂量(即4ma)的tDCS可能是未来试验的考虑因素。资助国家神经疾病和中风研究所。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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