This Phase 2b study will evaluate whether lesion network mapping-guided continuous theta burst stimulation (cTBS) can improve recovery after acute ischemic stroke. The treatment uses each participant's brain imaging to identify individualized stimulation targets related to stroke symptoms. Participants will receive either active cTBS or a sham procedure in addition to standard stroke care. The study will assess the efficacy and safety of this personalized brain stimulation approach and support planning for future confirmatory trials.
Acute ischemic stroke can lead to persistent motor impairment despite standard medical treatment and rehabilitation. The early post-stroke period may provide an important window for modulating brain network plasticity and supporting functional recovery. Continuous theta burst stimulation (cTBS), a patterned form of repetitive transcranial magnetic stimulation, can modulate cortical excitability over a short stimulation period and may enhance recovery when applied to clinically relevant motor networks. This Phase 2b study evaluates a personalized neuromodulation approach based on lesion network mapping. For each participant, the acute infarct lesion is identified on clinical brain imaging and mapped to a reference functional connectome to estimate lesion-associated brain networks. Candidate stimulation targets are selected from symptom-relevant cortical network nodes, with consideration of accessibility, safety, and electric-field modeling. Neuronavigation is used to guide coil placement and maintain targeting accuracy during treatment. Active treatment consists of lesion network mapping-guided cTBS delivered to individualized cortical targets using a figure-8 coil under neuronavigation. Sham stimulation follows the same imaging-based target selection, electric-field modeling, positioning, and procedural workflow, but uses a sham coil designed to mimic the sensory and acoustic features of stimulation without delivering a therapeutic magnetic field. This approach is intended to maintain blinding of participants and outcome assessors while isolating the effect of active stimulation. The study is designed to evaluate the efficacy and safety of individualized lesion network mapping-guided cTBS for recovery after acute ischemic stroke and to inform the design of future confirmatory trials.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
Individualized treatment targets are defined by outlining lesion areas on each patient's MRI and projecting them onto a normative functional connectivity map to identify symptom-specific connectivity disruptions within sensorimotor regions. Twice-daily treatments, administered over seven consecutive days, employ an "8"-shaped coil guided by neuronavigation for real-time targeting. For each target, a 40-second session delivers 600 pulses at an intensity of 80% of each participant's resting motor threshold (RMT), administered as 3-pulse bursts at 50 Hz, repeated at a theta frequency of 5 Hz.
Sham LNM-navigated cTBS follows the identical workflow, including MRI-based lesion mapping, target selection, electric-field modeling, and neuronavigation, but uses a sham figure-8 coil that mimics the sound and sensation of stimulation without generating a significant magnetic field. Participants receive two sham treatment sessions per day for seven consecutive days. Each session follows the same 40-second protocol timing and coil positioning as the active intervention, ensuring that participants and assessors remain blinded while no effective pulses are delivered.
Beijing Tiantan Hospital
Beijing, China
Proportion of patients achieving mRS 0-2
Time frame: Day 90 post-randomization
Proportion experiencing serious adverse events (SAEs)
Proportion experiencing serious adverse events (SAEs), including seizures
Time frame: Within 90 days post-randomization
Distribution shift in mRS scores
Time frame: Day 90 post-randomization
Proportion of patients achieving mRS 0-1
Time frame: Day 90 post-randomization
National Institutes of Health Stroke Scale (NIHSS) total score
Change in National Institutes of Health Stroke Scale (NIHSS) total score from baseline to 7 days post-randomization.
Time frame: Day 7 post-randomization
Fugl-Meyer Assessment (FMA) score
Change in Fugl-Meyer Assessment (FMA) score from baseline to 7 days post-randomization.
Time frame: Day 7 post-randomization
Barthel Index of Activities of Daily Living score
Time frame: Day 90 post-randomization
EQ-5D-5L
EuroQol five-dimensional five-level health questionnaire
Time frame: Day 90 post-randomization
Early neurological deterioration
Proportion of patients with neurological deterioration (defined as a ≥4-point increase in NIHSS score) within 7 days post-randomisation.
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TREATMENT
Masking
QUADRUPLE
Enrollment
60
Time frame: 7 days post-randomisation
Proportion of participants with insomnia
The proportion of participants with insomnia reported within 7 days after randomization.
Time frame: Within 7 days after randomization.
Proportion of participants with headache
The proportion of participants with headache reported within 7 days after randomization;
Time frame: Within 7 days after randomization;
Proportion of participants with symptomatic intracranial hemorrhage
The proportion of participants with symptomatic intracranial hemorrhage reported within 7 days after randomization.
Time frame: Within 7 days after randomization.
All-Cause Mortality
Proportion of patients who died from any cause
Time frame: Within 90 days post-randomization
Proportion with symptomatic stroke (ischemic or hemorrhagic)
Time frame: Within 90 days post-randomization
Any Adverse Events (AEs)
Proportion experiencing any adverse events
Time frame: Within 90 days post-randomization