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 Schlaug¹, Christy Cassarly², Jody A Feld³, Steve L Wolf⁴, Veronica T Rowe⁵, Stacy Fritz⁶, Pratik Y Chhatbar³, Anant Shinde¹, Zemin Su², Joseph P Broderick⁷, Richard Zorowitz⁸, Oluwole Awosika⁷, Dylan Edwards⁹, Chen Lin¹⁰, Gerard E Franciso¹¹, George F Wittenberg¹², Svetlana Pundik¹³, Christopher Gregory¹⁴, Michael R Borich⁴, Viswanathan Ramakrishnan², Wuwei Feng¹⁵

Affiliations

¹ Department of Neurology, University of Massachusetts Chan Medical School-Baystate, and Department of Biomedical Engineering, Institute of Applied Life Sciences, University of Massachusetts, Amherst, MA, USA.
² Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
³ Department of Neurology, School of Medicine, Duke University, Durham, NC, USA.
⁴ Department of Rehabilitation Medicine, Emory University, Atlanta, GA, USA.
⁵ Department of Occupational Therapy, Georgia State University, Atlanta, GA, USA.
⁶ Arnold School of Public Health, Physical Therapy Program, University of South Carolina, Columbia, SC, USA.
⁷ Department of Neurology and Rehabilitation Medicine, University of Cincinnati Gardner Neuroscience Institute, University of Cincinnati, Cincinnati, OH, USA.
⁸ Department of Rehabilitation Medicine, Georgetown University, Washington, DC, USA; MedStar National Rehabilitation Network, Washington, DC, USA.
⁹ Jefferson Moss Rehabilitation Research Institute, Thomas Jefferson University, Philadelphia, PA, USA.
¹⁰ Department of Neurology, University of Alabama, Birmingham, AL, USA; Birmingham Veterans Affairs Medical Center, Birmingham, AL USA.
¹¹ Department of Physical Medicine and Rehabilitation, University of Texas Health Science Center, University of Texas, Houston, TX, USA.
¹² Departments of Neurology, Physical Medicine & Rehabilitation, and Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Technology Enhancing Cognition and Health-Geriatric Research Education and Clinical Center and Human Engineering Research Labs, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA.
¹³ Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA; Department of Neurology, Case Western Reserve University, Cleveland, OH, USA.
¹⁴ Department of Health Science, Medical University of South Carolina, Charleston, SC, USA.
¹⁵ Department of Neurology, School of Medicine, Duke University, Durham, NC, USA. Electronic address: wayne.feng@duke.edu.

PMID: 40157380
DOI: 10.1016/S1474-4422(25)00044-4

Clinical Trial

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 et al. Lancet Neurol. 2025 May.

. 2025 May;24(5):400-412.

doi: 10.1016/S1474-4422(25)00044-4. Epub 2025 Mar 26.

Authors

Affiliations

¹ Department of Neurology, University of Massachusetts Chan Medical School-Baystate, and Department of Biomedical Engineering, Institute of Applied Life Sciences, University of Massachusetts, Amherst, MA, USA.
² Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
³ Department of Neurology, School of Medicine, Duke University, Durham, NC, USA.
⁴ Department of Rehabilitation Medicine, Emory University, Atlanta, GA, USA.
⁵ Department of Occupational Therapy, Georgia State University, Atlanta, GA, USA.
⁶ Arnold School of Public Health, Physical Therapy Program, University of South Carolina, Columbia, SC, USA.
⁷ Department of Neurology and Rehabilitation Medicine, University of Cincinnati Gardner Neuroscience Institute, University of Cincinnati, Cincinnati, OH, USA.
⁸ Department of Rehabilitation Medicine, Georgetown University, Washington, DC, USA; MedStar National Rehabilitation Network, Washington, DC, USA.
⁹ Jefferson Moss Rehabilitation Research Institute, Thomas Jefferson University, Philadelphia, PA, USA.
¹⁰ Department of Neurology, University of Alabama, Birmingham, AL, USA; Birmingham Veterans Affairs Medical Center, Birmingham, AL USA.
¹¹ Department of Physical Medicine and Rehabilitation, University of Texas Health Science Center, University of Texas, Houston, TX, USA.
¹² Departments of Neurology, Physical Medicine & Rehabilitation, and Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Technology Enhancing Cognition and Health-Geriatric Research Education and Clinical Center and Human Engineering Research Labs, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA.
¹³ Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA; Department of Neurology, Case Western Reserve University, Cleveland, OH, USA.
¹⁴ Department of Health Science, Medical University of South Carolina, Charleston, SC, USA.
¹⁵ Department of Neurology, School of Medicine, Duke University, Durham, NC, USA. Electronic address: wayne.feng@duke.edu.

PMID: 40157380
DOI: 10.1016/S1474-4422(25)00044-4

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.

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Conflict of interest statement

Declaration of interests WF received grant funding from the US National Institute of Health (NIH) for the present study as the contact Principal Investigator and other grants from the NIH and American Heart Association for other brain stimulation stroke recovery studies. He also received consulting fees from serving as the chair of the Data Safety Monitoring Board for North American Science Associates and being a scientific advisory member for Burke Rehabilitation Institute and California Institute of Regenerative Medicine. GS received grant support for the present study as a Multiple Principal Investigator from the NIH, grant support from the NIH for other brain stimulation recovery studies, and also received honorarium for grand rounds from academic institutions. JAF, SLW, VTR, SF, JPB, RZ, OA, PYC, AS, DE, CL, GEF, GFW, SP, CG, MRB, CC, ZS, and VR received grant support for their efforts as site Principal Investigators or co-investigators or key team members for the present study from the NIH since 2018. PYC also received other grant support from NIH (an R03 early career award). JPB received financial support and study medication from Novo Nordisk for an NIH-sponsored FASTEST study; consulting fees from Roche–Genentech, Brainsgate, and Basking Biosciences Department; and fees from his role on the Pharmacy and Therapeutics Committee for Kroger Prescription Plans. DE also received travel reimbursement from the American Academy of Neurology, Rehabilitation Medicine Society of Australia and New Zealand and Villa Beretta Rehabilitation Hospital, and Milan Polytechnic University; participated in data safety monitoring board or scientific advisory board for the Harvard Medical School, and served as an unpaid robotics special interest group co-chair for the World Federation of Neurorehabilitation. SF received grant support from the NIH for the present work as well as other grant support from the National Science Foundation and the NIH; consulting fees for participating in another NIH grant; and travel support for conferences from University of South Carolina. CG and CC also received other grant support from the NIH for other stroke recovery projects. CL acknowledged grant support from the Veteran Administration. GFW received travel reimbursement from NIH, National Science Foundation, and the Veterans Health Administration and served on advisory boards for two stroke rehabilitation product companies (NeuroInnovators and Myomo).

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical