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

Официальное название

Lesion Network Mapping-Navigated Continuous Theta-Burst Stimulation for Motor Recovery in Acute Ischemic Stroke: A Randomized, Double-Blind, Sham-Controlled, Multicentre Phase 3 Trial: MASTRE-3

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство LNM-navigated cTBS
  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).
• Устройство Sham cTBS
  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.

Первичные конечные точки

• Proportion of patients achieving mRS 0-2 [Срок оценки: Day 90 post-randomization]
• Proportion experiencing serious adverse events (SAEs) [Срок оценки: Within 90 days post-randomization]

Вторичные конечные точки (12)

• Distribution shift in modified Rankin Scale (mRS) score [Срок оценки: Day 90 post-randomization]
• Proportion of patients achieving mRS 0-1 [Срок оценки: Day 90 post-randomization]
• Change from baseline in National Institutes of Health Stroke Scale (NIHSS) total score at Day 7 [Срок оценки: Day 7 post-randomization]
• Change from baseline in Fugl-Meyer Assessment of Motor Recovery after Stroke motor score at Day 7 [Срок оценки: Day 7 post-randomization]
• Barthel Index for Activities of Daily Living score at Day 90 [Срок оценки: Day 90 post-randomization]
• EuroQol 5-Dimension 3-Level Questionnaire (EQ-5D-3L) health utility index score [Срок оценки: Day 90 post-randomization]
• Early neurological deterioration [Срок оценки: 7 days post-randomisation]
• Proportion of participants with insomnia [Срок оценки: Within 7 days after randomization.]
• Proportion of participants with headache [Срок оценки: Within 7 days after randomization;]
• Proportion of participants with symptomatic intracranial hemorrhage [Срок оценки: Within 7 days after randomization.]
• All-Cause Mortality [Срок оценки: Within 90 days post-randomization]
• Proportion with symptomatic stroke (ischemic or hemorrhagic) [Срок оценки: Within 90 days post-randomization]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing Tiantan Hospital — Пекин

Публикации

• Ding L, Liu H, Jing J, Jiang Y, Meng X, Chen Y, Zhao X, Niu H, Liu T, Wang Y, Li Z. Lesion Network Mapping for Neurological Deficit in Acute Ischemic Stroke. Ann Neurol. 2023 Sep;94(3):572-584. doi: 10.1002/ana.26721. Epub 2023 Jun 27. PMID 37314250

Идентификаторы

NCT: NCT07645586 · ZLRK202509

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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