Ischemic Stroke
Conditions
Keywords
ishchemic stroke, Lesion network mapping, Continuous theta-burst stimulation, Motor function, Neuronavigation
Brief summary
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.
Detailed description
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.
Interventions
DEVICELNM-navigated cTBS
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.
DEVICESham cTBS
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.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, care providers, investigators, and outcomes assessors are all blinded to treatment allocation. A separate, unblinded technician prepares and operates the stimulation device according to randomized codes but has no role in clinical assessments, data collection, or patient care beyond administering the sessions. Treatment codes remain concealed until database lock, except in predefined emergencies requiring unblinding for safety.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients achieving mRS 0-2 | Day 90 post-randomization | — |
| Proportion experiencing serious adverse events (SAEs) | Within 90 days post-randomization | Proportion experiencing serious adverse events (SAEs), including seizures |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distribution shift in modified Rankin Scale (mRS) score | Day 90 post-randomization | 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. |
| Proportion of patients achieving mRS 0-1 | Day 90 post-randomization | — |
| Change from baseline in National Institutes of Health Stroke Scale (NIHSS) total score at Day 7 | Day 7 post-randomization | Change in National Institutes of Health Stroke Scale (NIHSS) total score from baseline to Day 7 post-randomization. The NIHSS total score ranges from 0 to 42. Higher scores indicate a more severe neurological deficit and worse outcome. Change is calculated as the Day 7 score minus the baseline score; a negative change indicates improvement. |
| Change from baseline in Fugl-Meyer Assessment of Motor Recovery after Stroke motor score at Day 7 | Day 7 post-randomization | 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. |
| Barthel Index for Activities of Daily Living score at Day 90 | Day 90 post-randomization | 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. |
| EuroQol 5-Dimension 3-Level Questionnaire (EQ-5D-3L) utility index score | Day 90 post-randomization | EQ-5D-3L utility index score at Day 90 post-randomization. Health states based on the five EQ-5D dimensions are converted to a utility index using the applicable EQ-5D-3L value set. Higher scores indicate better health-related quality of life. |
| Early neurological deterioration | 7 days post-randomisation | Proportion of patients with neurological deterioration (defined as a ≥4-point increase in NIHSS score) within 7 days post-randomisation. |
| Proportion of participants with insomnia | Within 7 days after randomization. | The proportion of participants with insomnia reported within 7 days after randomization. |
| Proportion of participants with headache | Within 7 days after randomization; | The proportion of participants with headache reported within 7 days after randomization; |
| Proportion of participants with symptomatic intracranial hemorrhage | Within 7 days after randomization. | The proportion of participants with symptomatic intracranial hemorrhage reported within 7 days after randomization. |
| All-Cause Mortality | Within 90 days post-randomization | Proportion of patients who died from any cause |
| Proportion with symptomatic stroke (ischemic or hemorrhagic) | Within 90 days post-randomization | — |
| Any Adverse Events (AEs) | Within 90 days post-randomization | Proportion experiencing any adverse events |
Countries
China
Contacts
CONTACTLingling Ding, MD
CONTACTZixiao Li, MD
Outcome results
None listed