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

IntroductionIntermittent 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 analysisA 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 disseminationEthical 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 numberNCT04034069.

The Effectiveness of Intermittent Theta Burst Stimulation for Stroke Patients With Upper Limb Impairments: A Systematic Review and Meta-Analysis

“…In all of the trials considered, the items' selective reporting were rated as low risk of bias except one ( 29 ). Random sequence generation or allocation concealment scored a high risk of bias or unclear risk in four of the included studies, which led to the error of the result to increase ( 15 , 21 , 23 , 25 ).…”

“…According to certain studies, the blinding of outcome assessment was not specified adequately, resulting in a score that was unclear or high in the detection bias ( 22 , 23 , 25 , 28 , 30 , 32 ). In some studies, incomplete outcome data were scored as high risk of bias or unclear risk, indicating that the data was incomplete or missing ( 17 , 22 , 23 , 28 , 29 ) (see Figures 2 , 3 ).…”

Priming Intermittent Theta Burst Stimulation for Hemiparetic Upper Limb After Stroke: A Randomized Controlled Trial

“…The study protocol was preregistered (NCT04034069) and published. 18 This article followed the CONSORT reporting guideline for clinical trials. 19…”

Effect of priming on adjunctive repetitive transcranial magnetic stimulation in treatment of late-life depression: protocol of a prospective randomized sham-controlled study

“…Priming rTMS is a novel stimulation method which has been studied in other conditions like stroke, auditory verbal hallucinations, and adult depression giving positive results. [19][20][21] Old age is reported as a predictor of poor response to rTMS in earlier studies. However, the recent studies have come up with contradictory findings of higher age being the better predictor of response.…”