Effects of priming intermittent theta burst stimulation on upper limb motor recovery after stroke : study protocol for a proof-of-concept randomised controlled trial

Abstract

Introduction Intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS), delivered to the ipsilesional primary motor cortex (M1), appears to enhance the brain's response to rehabilitative training in patients with stroke. However, its clinical utility is highly subject to variability in different protocols. New evidence has reported that preceding iTBS, with continuous theta burst stimulation (cTBS) may stabilise and even boost the facilitatory effect of iTBS on the stimulated M1, via metaplasticity. The aim of this study is to investigate the effects of iTBS primed with cTBS (ie, priming iTBS), in addition to robot-assisted training (RAT), on the improvement of the hemiparetic upper limb functions of stroke patients and to explore potential sensorimotor neuroplasticity using electroencephalography (EEG). Methods and analysis A three-arm, subjects and assessors-blinded, randomised controlled trial will be performed with patients with chronic stroke. An estimated sample of 36 patients will be needed based on the prior sample size calculation. All participants will be randomly allocated to receive 10 sessions of rTMS with different TBS protocols (cTBS+iTBS, sham cTBS+iTBS and sham cTBS+sham iTBS), three to five sessions per week, for 2-3 weeks. All participants will receive 60 min of RAT after each stimulation session. Primary outcomes will be assessed using Fugl-Meyer Assessment-Upper Extremity scores and Action Research Arm Test. Secondary outcomes will be assessed using kinematic outcomes generated during RAT and EEG. Ethics and dissemination Ethical approval has been obtained from The Human Subjects Ethics Sub-committee, University Research Committee of The Hong Kong Polytechnic University (reference number: HSEARS20190718003). The results yielded from this study will be presented at international conferences and sent to a peer-review journal to be considered for publication. Trial registration number NCT04034069.