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

Phase 3Not Yet RecruitingNCT07645586

Beijing Tiantan Hospital584 enrolled

Overview

This Phase 3 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 whether this personalized brain stimulation approach improves functional recovery and is safe for patients after 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Interventions

LNM-navigated cTBSDEVICE

Individualized treatment targets are defined by outlining each patient's acute infarct lesion on MRI and projecting it onto a normative functional connectivity map to identify symptom-relevant network nodes within sensorimotor regions. Treatment is delivered over seven consecutive days using a figure-8 coil guided by neuronavigation. cTBS consists of 3-pulse bursts at 50 Hz, repeated at 5 Hz, for a total of 600 pulses over 40 seconds, delivered at 80% of the resting motor threshold (RMT).

Sham cTBSDEVICE

Sham stimulation follows the same MRI-based lesion mapping, target selection, neuronavigation workflow, coil positioning, timing, acoustic noise, and treatment course as the active group, but uses a sham figure-8 coil that mimics stimulation without generating a significant magnetic field. This design helps maintain blinding of participants and assessors while ensuring that no effective magnetic stimulation is delivered.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age 18-80 years. 2. Ischemic stroke onset within the past 14 days. 3. Unilateral, supratentorial ischemic stroke confirmed by CT or MRI. 4. Pre-stroke modified Rankin Scale (mRS) score of 0-1. 5. 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. 6. Written informed consent signed by the patient or the patient's legally authorized representative. Exclusion Criteria: 1. Contraindications to TMS (e.g. cranial metallic foreign bodies, cardiac pacemaker, implanted drug pump, cochlear implant). 2. History of epilepsy or seizure, intracranial hypertension, tumor, or other serious neurological disease. 3. Midline shift or parenchymal mass effect on cranial CT or other imaging. 4. CT or MRI evidence of bilateral acute cerebral infarction or infratentorial acute infarction (brainstem or cerebellum). 5. Evidence of acute intracranial hemorrhage, including spontaneous intracerebral hemorrhage, epidural hematoma, subdural hematoma, intraventricular hemorrhage, or subarachnoid hemorrhage. 6. Pre-stroke mRS ≥ 2. 7. Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg despite antihypertensive treatment. 8. Pregnant or breastfeeding women, or women planning pregnancy within 90 days. 9. Severe psychiatric disorders or dementia (or other conditions) precluding informed consent or follow-up. 10. Concomitant malignant tumor or severe systemic disease with life expectancy \< 90 days. 11. Participation in any other interventional clinical study within 30 days before randomization, or currently enrolled in such a study.

Outcomes

Primary Outcomes

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

Secondary Outcomes

Distribution shift in modified Rankin Scale (mRS) score

Distribution shift in modified Rankin Scale (mRS) scores at Day 90 post-randomization. The mRS is an ordinal disability scale ranging from 0 to 6, where 0 indicates no symptoms and 6 indicates death. Higher scores indicate worse functional outcome.

Time frame: Day 90 post-randomization

Proportion of patients achieving mRS 0-1

Time frame: Day 90 post-randomization

Proportion of Participants With Early Neurological Improvement at Day 7

Proportion of participants with early neurological improvement, defined as a decrease of ≥4 points in the National Institutes of Health Stroke Scale (NIHSS) total score from baseline to Day 7 post-randomization or an NIHSS total score of 0-1 at Day 7. The NIHSS total score ranges from 0 to 42, with higher scores indicating more severe neurological deficits. Participants meeting either criterion will be classified as having early neurological improvement.

Time frame: Day 7 post-randomization

Change from baseline in Fugl-Meyer Assessment of Motor Recovery after Stroke motor score at Day 7

Change in Fugl-Meyer Assessment of Motor Recovery after Stroke motor score from baseline to Day 7 post-randomization. The Fugl-Meyer Assessment motor score ranges from 0 to 100, including an upper extremity motor score ranging from 0 to 66 and a lower extremity motor score ranging from 0 to 34. Higher scores indicate better motor recovery and less motor impairment. Change is calculated as the Day 7 score minus the baseline score; a positive change indicates improvement.

Time frame: Day 7 post-randomization

Barthel Index for Activities of Daily Living score at Day 90

Barthel Index for Activities of Daily Living score at Day 90 post-randomization. The Barthel Index assesses independence in 10 activities of daily living and mobility activities. Total scores range from 0 to 100; higher scores indicate greater independence and better functional outcome.

Time frame: Day 90 post-randomization

EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Utility Index Score at Day 90

EQ-5D-5L utility index score at Day 90 post-randomization. The EQ-5D-5L assesses health status across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, with five levels of severity for each dimension. The resulting health states are converted into a utility index score using the applicable EQ-5D-5L value set. Higher scores indicate better health-related quality of life.

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.

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

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts