Lesion network mapping navigated continuous theta burst stimulation for motor recovery in acute ischaemic stroke (MASTRE): rationale and design of a randomised double-blind controlled multicentre phase 2 trial

BACKGROUND: In stroke recovery, the heterogeneity of lesions and symptoms makes it challenging to target neuromodulation precisely. Conventional one-size-fits-all neuromodulation approaches yield inconsistent outcomes, highlighting the need for precision strategies, such as lesion network mapping (LNM), to identify patient-specific symptom-related networks. AIM: To evaluate the efficacy and safety of LNM-guided continuous theta-burst stimulation (cTBS) in improving motor recovery in patients with acute ischaemic stroke (AIS) treated within 14 days of symptom onset. DESIGN: The mapping navigated continuous theta-burst stimulation for motor recovery (MASTRE) trial is a multicentre, randomised, double-blind, sham-controlled Phase 2 study. Eligible participants will be randomly assigned (1:1) to receive either active LNM-guided cTBS or sham stimulation. For each participant, individualised stimulation targets will be determined through LNM, and real-time neuronavigation will be used to ensure precise modulation of the disrupted sensorimotor network. Treatment will consist of one daily session for seven consecutive days. In each session, cTBS will be delivered as bursts of three pulses at 50 Hz, repeated every 200 ms for 40 s. STUDY OUTCOMES: The primary efficacy outcome is the change in Fugl-Meyer Assessment total motor score from baseline to Day 7 post-randomisation. Safety assessments will include symptomatic intracranial haemorrhage and adverse events, which will be monitored through Day 90 post-randomisation. DISCUSSION: The MASTRE study introduces an innovative approach to optimise cTBS therapy in AIS patients by employing LNM to identify patient-specific targets within affected sensorimotor networks. Results from this trial may inform a new precision neurorehabilitation framework, promoting personalised therapeutic interventions tailored to individual neural connectivity profiles. TRIAL REGISTRATION NUMBER: NCT06400407.