Discussion
stroke, ischemic stroke, upper limb motor rehabilitation, aphasia, subacute stroke
DISORDERS, STROKE, DYSFUNCTION, ISCHEMIC STROKE
The BOSS-STROKE trial is an exploratory phase-3 trial to provide positive evidence for the main hypothesis, i.e., brain-oscillation-synchronized rTMS is more effective than standard non-brain-oscillation-synchronized rTMS and sham rTMS in improving arm-/hand function of patients with early subacute stroke. We hypothesize that synchronization of rTMS with the phase of the ongoing sensorimotor oscillation indicating high corticospinal excitability leads to significantly stronger improvement of paretic upper limb motor function than the same rTMS protocol non‐synchronized to the ongoing sensorimotor oscillation or sham stimulation. The objective of this clinical trial is to investigate the therapeutic efficacy of rTMS synchronization to targeted EEG‐states in the early subacute phase after ischemic stroke to improve upper limb motor rehabilitation.The risk to patients participating in this trial is low and not exceeding the expected benefit: Early subacute stroke patients receiving real rTMS are likely to have a therapeutic benefit on their neurorehabilitation [In case of the confirmation of the main hypothesis for the primary endpoint of this trial, i.e., brain-oscillation-synchronized rTMS results in a higher FMA-UE immediately after the last treatment session compared to the two control conditions, non-brain-oscillation-synchronized rTMS and sham rTMS, a confirmatory trial will be conducted. The confirmatory trial will seek to provide firm evidence for efficacy and safety of brain-oscillation synchronized rTMS in an even broader range of early subacute stroke patients with a broader variety of arm-/hand dysfunction severity. The anticipated clinical impact of the confirmatory trial is to provide firm evidence for superiority of brain-oscillation-synchronized personalized therapeutic brain stimulation with respect to clinically relevant outcome of arm-/hand function in early subacute stroke patients. If successful this will lead to a significant expansion of the treatment repertoire of this patient population in the early neurorehabilitation setting.In summary, the results of this trial will be of outstanding importance for the establishment of novel personalized brain‐oscillation synchronized rTMS therapy protocols, which likely will lead to a paradigm shift in non-invasive brain stimulation. This new therapy option will lead to a significant expansion of the recovery repertoire of patients suffering from a stroke in the early neurorehabilitation setting that might be expanded to a variety of other deficits (e.g., aphasia or neglect) and other brain network disorders in further confirmatory trials.