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Neurological Research and Practice

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01-12-2022 | Stroke | Clinical trial protocol

A multicenter, randomized, double-blind, placebo-controlled trial to test efficacy and safety of transcranial direct current stimulation to the motor cortex after stroke (NETS): study protocol

Author: The NETS Trial Collaboration Group

Published in: Neurological Research and Practice | Issue 1/2022

Abstract

Introduction

The WHO estimates that each year 5 million people are left permanently disabled after stroke. Adjuvant treatments to promote the effects of rehabilitation are urgently needed. Cortical excitability and neuroplasticity can be enhanced by non-invasive brain stimulation but evidence from sufficiently powered, randomized controlled multi-center clinical trials is absent.

Methods

Neuroregeneration enhanced by transcranial direct current stimulation (tDCS) in stroke (NETS) tested efficacy and safety of anodal tDCS to the primary motor cortex of the lesioned hemisphere in the subacute phase (day 5–45) after cerebral ischemia. Stimulation was combined with standardized rehabilitative training and repeatedly applied in 10 sessions over a period of 2 weeks in a planned sample of 120 patients. Primary outcome parameter was upper-extremity function at the end of the 2-weeks intervention period of active treatment or placebo (1:1 randomization), measured by the upper-extremity Fugl-Meyer assessment. Sustainability of the treatment effect was evaluated by additional follow-up visits after 30 and 90 days. Further secondary endpoints included metrics of arm and hand function, stroke impact scale, and the depression module of the patient health questionnaire.

Perspective

NETS was aimed at providing evidence for an effective and safe adjuvant treatment for patients after stroke.

Trial registration: ClinicalTrials.gov Identifier NCT00909714. Registered May 28, 2009.

Available only for authorised users

Allman, C., Amadi, U., Winkler, A. M., Wilkins, L., Filippini, N., Kischka, U., Stagg, C. J., & Johansen-Berg, H. (2016). Ipsilesional anodal tDCS enhances the functional benefits of rehabilitation in patients after stroke. Science Translational Medicine, 8(330), 330re331. https://doi.org/10.1126/scitranslmed.aad5651CrossRef

Bikson, M., Brunoni, A. R., Charvet, L. E., Clark, V. P., Cohen, L. G., Deng, Z. D., Dmochowski, J., Edwards, D. J., Frohlich, F., Kappenman, E. S., Lim, K. O., Loo, C., Mantovani, A., McMullen, D. P., Parra, L. C., Pearson, M., Richardson, J. D., Rumsey, J. M., Sehatpour, P., … Lisanby, S. H. (2018). Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop. Brain Stimulation, 11(3), 465–480. https://doi.org/10.1016/j.brs.2017.12.008CrossRefPubMed

Boggio, P. S., Nunes, A., Rigonatti, S. P., Nitsche, M. A., Pascual-Leone, A., & Fregni, F. (2007). Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restorative Neurology and Neuroscience, 25(2), 123–129.PubMed

Brown, J. A., Lutsep, H. L., Weinand, M., & Cramer, S. C. (2006). Motor cortex stimulation for the enhancement of recovery from stroke: A prospective, multicenter safety study. Neurosurgery, 58(3), 464–473.CrossRefPubMed

Ford, G. A., Bhakta, B. B., Cozens, A., Hartley, S., Holloway, I., Meads, D., Pearn, J., Ruddock, S., Sackley, C. M., Saloniki, E. C., Santorelli, G., Walker, M. F., & Farrin, A. J. (2019). Safety and efficacy of co-careldopa as an add-on therapy to occupational and physical therapy in patients after stroke (DARS): A randomised, double-blind, placebo-controlled trial. The Lancet Neurology, 18(6), 530–538. https://doi.org/10.1016/S1474-4422(19)30147-4CrossRefPubMedPubMedCentral

Gandiga, P. C., Hummel, F. C., & Cohen, L. G. (2006). Transcranial DC stimulation (tDCS): A tool for double-blind sham-controlled clinical studies in brain stimulation. Clinical Neurophysiology, 117(4), 845–850.CrossRefPubMed

Harvey, R. L., Edwards, D., Dunning, K., Fregni, F., Stein, J., Laine, J., Rogers, L. M., Vox, F., Durand-Sanchez, A., Bockbrader, M., Goldstein, L. B., Francisco, G. E., Kinney, C. L., Liu, C. Y., Ryan, S., Morales-Quezada, L., Worthen-Chaudhari, L., Labar, D., Schambra, H., … Pratt, W. (2018). Randomized sham-controlled trial of navigated repetitive transcranial magnetic stimulation for motor recovery in stroke: The NICHE trial. Stroke, 49(9), 2138–2146. https://doi.org/10.1161/STROKEAHA.117.020607CrossRefPubMed

Heise, K. F., Niehoff, M., Feldheim, J. F., Liuzzi, G., Gerloff, C., & Hummel, F. C. (2014). Differential behavioral and physiological effects of anodal transcranial direct current stimulation in healthy adults of younger and older age. Frontiers in Aging Neuroscience, 6, 146. https://doi.org/10.3389/fnagi.2014.00146CrossRefPubMedPubMedCentral

Hummel, F., Celnik, P., Giraux, P., Floel, A., Wu, W. H., Gerloff, C., & Cohen, L. G. (2005). Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain, 128(Pt 3), 490–499. https://doi.org/10.1093/brain/awh369CrossRefPubMed

10.

Ilic, N. V., Dubljanin-Raspopovic, E., Nedeljkovic, U., Tomanovic-Vujadinovic, S., Milanovic, S. D., Petronic-Markovic, I., & Ilic, T. V. (2016). Effects of anodal tDCS and occupational therapy on fine motor skill deficits in patients with chronic stroke. Restorative Neurology and Neuroscience, 34(6), 935–945. https://doi.org/10.3233/RNN-160668CrossRefPubMed

11.

Jefferson, S. C., Clayton, E. R., Donlan, N. A., Kozlowski, D. A., Jones, T. A., & Adkins, D. L. (2016). Cortical stimulation concurrent with skilled motor training improves forelimb function and enhances motor cortical reorganization following controlled cortical impact. Neurorehabilitation and Neural Repair, 30(2), 155–158. https://doi.org/10.1177/1545968315600274CrossRefPubMed

12.

Kim, S. Y., Hsu, J. E., Husbands, L. C., Kleim, J. A., & Jones, T. A. (2018). Coordinated plasticity of synapses and astrocytes underlies practice-driven functional vicariation in peri-infarct motor cortex. The Journal of Neuroscience, 38(1), 93–107. https://doi.org/10.1523/JNEUROSCI.1295-17.2017CrossRefPubMedPubMedCentral

13.

Koch, P. J., Park, C. H., Girard, G., Beanato, E., Egger, P., Evangelista, G. G., Lee, J., Wessel, M. J., Morishita, T., Koch, G., Thiran, J. P., Guggisberg, A. G., Rosso, C., Kim, Y. H., & Hummel, F. C. (2021). The structural connectome and motor recovery after stroke: Predicting natural recovery. Brain, 144(7), 2107–2119. https://doi.org/10.1093/brain/awab082CrossRefPubMedPubMedCentral

14.

Krakauer, J. W. (2006). Motor learning: Its relevance to stroke recovery and neurorehabilitation. Current Opinion in Neurology, 19(1), 84–90.CrossRefPubMed

15.

Lotze, M., Markert, J., Sauseng, P., Hoppe, J., Plewnia, C., & Gerloff, C. (2006). The role of multiple contralesional motor areas for complex hand movements after internal capsular lesion. Journal of Neuroscience, 26(22), 6096–6102. https://doi.org/10.1523/JNEUROSCI.4564-05.2006CrossRefPubMed

16.

Nitsche, M. A., Seeber, A., Frommann, K., Klein, C. C., Rochford, C., Nitsche, M. S., Fricke, K., Liebetanz, D., Lang, N., Antal, A., Paulus, W., & Tergau, F. (2005). Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex. The Journal of Physiology, 568, 291–303.CrossRefPubMedCentralPubMed

17.

O’Brien, A. T., Bertolucci, F., Torrealba-Acosta, G., Huerta, R., Fregni, F., & Thibaut, A. (2018). Non-invasive brain stimulation for fine motor improvement after stroke: A meta-analysis. European Journal of Neurology, 25(8), 1017–1026. https://doi.org/10.1111/ene.13643CrossRefPubMed

18.

Page, S. J., Fulk, G. D., & Boyne, P. (2012). Clinically important differences for the upper-extremity Fugl-Meyer Scale in people with minimal to moderate impairment due to chronic stroke. Physical Therapy, 92(6), 791–798. https://doi.org/10.2522/ptj.20110009CrossRefPubMed

19.

Teskey, G. C., Flynn, C., Goertzen, C. D., Monfils, M. H., & Young, N. A. (2003). Cortical stimulation improves skilled forelimb use following a focal ischemic infarct in the rat. Neurological Research, 25(8), 794–800.CrossRefPubMed

20.

Ward, N. S. (2006). The neural substrates of motor recovery after focal damage to the central nervous system. Archives of Physical Medicine and Rehabilitation, 87(12 Suppl 2), S30-35.PubMed

Title: A multicenter, randomized, double-blind, placebo-controlled trial to test efficacy and safety of transcranial direct current stimulation to the motor cortex after stroke (NETS): study protocol
Author: The NETS Trial Collaboration Group
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Stroke
Neurorehabilitation
Published in: Neurological Research and Practice / Issue 1/2022
Electronic ISSN: 2524-3489
DOI: https://doi.org/10.1186/s42466-022-00171-2

At a glance: The STEP trials

Springer Medicine

A multicenter, randomized, double-blind, placebo-controlled trial to test efficacy and safety of transcranial direct current stimulation to the motor cortex after stroke (NETS): study protocol

Abstract

Introduction

Methods

Perspective

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Methods

Perspective

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