Personalized upper limb training combined with anodal-tDCS for sensorimotor recovery in spastic hemiparesis: study protocol for a randomized controlled trial

Mindy F Levin, Melanie C Baniña, Silvi Frenkel-Toledo, Sigal Berman, Nachum Soroker, John M Solomon, Dario G Liebermann, Mindy F Levin, Melanie C Baniña, Silvi Frenkel-Toledo, Sigal Berman, Nachum Soroker, John M Solomon, Dario G Liebermann

Abstract

Background: Recovery of voluntary movement is a main rehabilitation goal. Efforts to identify effective upper limb (UL) interventions after stroke have been unsatisfactory. This study includes personalized impairment-based UL reaching training in virtual reality (VR) combined with non-invasive brain stimulation to enhance motor learning. The approach is guided by limiting reaching training to the angular zone in which active control is preserved ("active control zone") after identification of a "spasticity zone". Anodal transcranial direct current stimulation (a-tDCS) is used to facilitate activation of the affected hemisphere and enhance inter-hemispheric balance. The purpose of the study is to investigate the effectiveness of personalized reaching training, with and without a-tDCS, to increase the range of active elbow control and improve UL function.

Methods: This single-blind randomized controlled trial will take place at four academic rehabilitation centers in Canada, India and Israel. The intervention involves 10 days of personalized VR reaching training with both groups receiving the same intensity of treatment. Participants with sub-acute stroke aged 25 to 80 years with elbow spasticity will be randomized to one of three groups: personalized training (reaching within individually determined active control zones) with a-tDCS (group 1) or sham-tDCS (group 2), or non-personalized training (reaching regardless of active control zones) with a-tDCS (group 3). A baseline assessment will be performed at randomization and two follow-up assessments will occur at the end of the intervention and at 1 month post intervention. Main outcomes are elbow-flexor spatial threshold and ratio of spasticity zone to full elbow-extension range. Secondary outcomes include the Modified Ashworth Scale, Fugl-Meyer Assessment, Streamlined Wolf Motor Function Test and UL kinematics during a standardized reach-to-grasp task.

Discussion: This study will provide evidence on the effectiveness of personalized treatment on spasticity and UL motor ability and feasibility of using low-cost interventions in low-to-middle-income countries.

Trial registration: ClinicalTrials.gov, ID: NCT02725853 . Initially registered on 12 January 2016.

Keywords: Neurorehabilitation; Spasticity; Spatial threshold; Stroke; tDCS.

Conflict of interest statement

Ethics approval and consent to participate

Ethical approval was obtained from the appropriate ethics committees of each study site prior to the beginning of the study. The Centre de Recherche Interdisciplinaire en Réadaptation du Montréal Métropolitain (Montréal, QC, Canada) approved the study for the Jewish Rehabilitation Hospital and the Institut de Réadaptation Gingras-Lindsay de Montréal (CRIR1112-1115). The Institutional Ethics Review Board of Loewenstein Rehabilitation Hospital (Ra’anana, Israel) approved the study for the Loewenstein Rehabilitation Hospital (000-11-15-LOE) and the Institutional Ethics Committee of the Tel Aviv University (Tel Aviv, Israel). The Institutional Ethics Committee of Kasturba Hospital (Manipal, India) approved the study for the Kasturba Medical Hospital (IEC-32/2016). The trial was registered with the ClinicalTrials.gov registry in USA on 12 January 2016 with the trial registration number NCT02725853. The SPIRIT guidelines for implementation of study protocols were followed (Fig. 2 and Additional file 1) [42]. Written informed consent will be obtained from each participant.

Adverse effects will be documented and reported to the co-PIs. If adverse effects occur then participants will be withdrawn from their allocated treatment but included in the measurement battery according to the intention-to-treat principle. All protocol modifications will be registered with ClinicalTrials.gov.

Consent for publication

Not applicable. No individual data are contained in the manuscript.

Competing interests

Jintronix will provide licenses for use of their gaming system and technical support and servers. MFL holds a US patent for the MSRT analysis. The remaining authors declare that they have no competing interests or any conflicts of interest in the authorship or publication of this study.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Spatial thresholds (STs) in healthy and stroke participants. a The tonic stretch reflex threshold (TSRT) can be regulated throughout a range (filled bar) that exceeds the biomechanical range of the joint (open bar). Relaxation and active force can be produced at any angle within the biomechanical range. b The intersection of the diagonal line with the zero-velocity line defines the TSRT. In healthy subjects, TSRT lies outside of the biomechanical range of the joint (arrow) during the relaxed state. c In patients with stroke, TSRT may lie within the biomechanical range in the relaxed state, defining the joint angle at which spasticity begins to appear (spasticity zone). In the other joint ranges, spasticity is not present (active zone)
Fig. 2
Fig. 2
Schedule of enrollment, interventions and assessments. Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) flow diagram of study enrollment, interventions and assessments
Fig. 3
Fig. 3
Jintronix virtual reality (VR) games used in the intervention. a Fish Frenzy game requires the player to trace a three-dimensional (3D) trajectory by moving a fish on the screen in different shapes. b Kitchen Cleanup game requires forward reaching towards kitchen cutlery and returning them to shelves and drawers. c Garden Grab game requires lateral reaching while planting seeds, harvesting and transferring tomatoes to baskets. d Catch, Carry, Drop game requires bilateral coordination while catching apples, carrying and dropping them into a container
Fig. 4
Fig. 4
Montreal Stretch Reflex Threshold (MSRT) device. The MSRT is a portable, clinical device consisting of a two-channel electromyography (EMG) system, an electrogoniometer and dedicated software implemented on a laptop computer

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