A Phase 3 Trial of Lesion Network Mapping-Guided cTBS for Motor Recovery After Acute Ischemic Stroke

Acute ischemic stroke often leads to persistent motor impairment despite standard medical treatment and rehabilitation. The early post-stroke period may represent an important window for modulating brain network plasticity and promoting 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 support recovery when applied to clinically relevant motor networks.

This 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 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.

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 while isolating the effect of active stimulation.

This Phase 3 trial evaluates the efficacy and safety of individualized lesion network mapping-guided cTBS for recovery after acute ischemic stroke.

Inclusion criteria

• Age 18-80 years.
• Ischemic stroke onset within the past 14 days.
• Unilateral, supratentorial ischemic stroke confirmed by CT or MRI.
• Pre-stroke modified Rankin Scale (mRS) score of 0-1.
• NIH Stroke Scale (NIHSS) total score 6-25, with item 1a ≤ 1 point, and at least one of items 5a, 5b, 6a, or 6b ≥ 2 points.
• Written informed consent signed by the patient or the patient's legally authorized representative.

Exclusion criteria

• Contraindications to TMS (e.g. cranial metallic foreign bodies, cardiac pacemaker, implanted drug pump, cochlear implant).
• History of epilepsy or seizure, intracranial hypertension, tumor, or other serious neurological disease.
• Midline shift or parenchymal mass effect on cranial CT or other imaging.
• CT or MRI evidence of bilateral acute cerebral infarction or infratentorial acute infarction (brainstem or cerebellum).
• Evidence of acute intracranial hemorrhage, including spontaneous intracerebral hemorrhage, epidural hematoma, subdural hematoma, intraventricular hemorrhage, or subarachnoid hemorrhage.
• Pre-stroke mRS ≥ 2.
• Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg despite antihypertensive treatment.
• Pregnant or breastfeeding women, or women planning pregnancy within 90 days.
• Severe psychiatric disorders or dementia (or other conditions) precluding informed consent or follow-up.
• Concomitant malignant tumor or severe systemic disease with life expectancy < 90 days.
• Participation in any other interventional clinical study within 30 days before randomization, or currently enrolled in such a study.