Ischemic StrokePhase 2MASTRE-2NCT07645560
A Phase 2b Trial of Lesion Network Mapping-Guided cTBS for Motor Recovery After Acute Ischemic Stroke
A Phase 2 study testing LNM-navigated cTBS in people with Ischemic Stroke, run by Beijing Tiantan Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- LNM-navigated cTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 26 Aug 2026to 30 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Zixiao Li, MD contact
China1 site
Beijing Tiantan Hospital
Beijing, 100070
Lingling Ding, MD, 008613552358752, dinglingling@bjtth.org
Zixiao Li, MD, lizixiao2008@hotmail.com
About this study
Official title: Lesion Network Mapping-Navigated Continuous Theta-Burst Stimulation for Motor Recovery in Acute Ischemic Stroke: A Randomized, Double-Blind, Sham-Controlled, Multicentre Phase 2b Trial: MASTRE-2
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.
Read the 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.
- Conditions
- Ischemic Stroke
- Being tested
- LNM-navigated cTBS, Sham cTBS
- Keywords
- ishchemic stroke, Lesion network mapping, Continuous theta-burst stimulation, Motor function, Neuronavigation
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LNM-navigated cTBSDevice
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 cTBSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| LNM-navigated cTBS group | Experimental | Patients receive two daily sessions for 7 consecutive days. Each session uses a figure-8 coil under neuronavigation to deliver 3-pulse bursts at 50 Hz, repeated at 5 Hz (continuous theta burst) for a total of 600 pulses in 40 seconds per target. Targets are individualized via lesion network mapping of the patient's acute infarct, selecting symptom-relevant network nodes. Stimulus intensity is set at 80% of the resting motor threshold. Receives: Device: LNM-navigated cTBS |
| Sham cTBS group | Sham comparator | Procedures mimic the active group in coil positioning, timing, navigation, acoustic noise, and session schedule, but use a sham coil that produces no effective magnetic field. Receives: Device: Sham cTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients achieving mRS 0-2
Measured: Day 90 post-randomization
Proportion experiencing serious adverse events (SAEs)
Proportion experiencing serious adverse events (SAEs), including seizures
Measured: Within 90 days post-randomization
Secondary outcomes (13)
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.
Measured: Day 90 post-randomization
Proportion of patients achieving mRS 0-1
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 7 days post-randomisation
Proportion of participants with insomnia
The proportion of participants with insomnia reported within 7 days after randomization.
Measured: Within 7 days after randomization.
Proportion of participants with headache
The proportion of participants with headache reported within 7 days after randomization;
Measured: 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.
Measured: Within 7 days after randomization.
All-Cause Mortality
Proportion of patients who died from any cause
Measured: Within 90 days post-randomization
Proportion with symptomatic stroke (ischemic or hemorrhagic)
Measured: Within 90 days post-randomization
Any Adverse Events (AEs)
Proportion experiencing any adverse events
Measured: Within 90 days post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2026
- Study start26 Aug 2026 (estimated)
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zi-Xiao Li, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07645560
- Sponsor's protocol ID
- KY2025-087
- Acronym
- MASTRE-2
- Status last verified
- Aug 2026
- First submitted
- 9 Jun 2026
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37314250
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lesion Network Mapping-Navigated Continuous Theta-Burst Stimulation for Motor Recovery in Acute Ischemic Stroke: A Randomized, Double-Blind, Sham-Controlled, Multicentre Phase 2b Trial: MASTRE-2
- ClinicalTrials.gov ID
- NCT07645560
- Acronym / sponsor ID
- MASTRE-2 / KY2025-087
- Conditions
- Ischemic Stroke
- Keywords
- ishchemic stroke, Lesion network mapping, Continuous theta-burst stimulation, Motor function, Neuronavigation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Study start
- 26 Aug 2026 (estimated)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 12 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LNM-navigated cTBS group | Experimental | Device: LNM-navigated cTBSPatients receive two daily sessions for 7 consecutive days. Each session uses a figure-8 coil under neuronavigation to deliver 3-pulse bursts at 50 Hz, repeated at 5 Hz (continuous theta burst) for a total of 600 pulses in 40 seconds per target. Targets are individualized via lesion network mapping of the patient's acute infarct, selecting symptom-relevant network nodes. Stimulus intensity is set at 80% of the resting motor threshold. |
| Sham cTBS group | Sham comparator | Device: Sham cTBSProcedures mimic the active group in coil positioning, timing, navigation, acoustic noise, and session schedule, but use a sham coil that produces no effective magnetic field. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LNM-navigated cTBSIndividualized 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. | Device | LNM-navigated cTBS group |
| Sham cTBSSham 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. | Device | Sham cTBS group |
Primary outcome
Proportion of patients achieving mRS 0-2
Time frame: Day 90 post-randomization
Proportion experiencing serious adverse events (SAEs)
Time frame: Within 90 days post-randomization
Proportion experiencing serious adverse events (SAEs), including seizures
13 secondary outcomes
Distribution shift in modified Rankin Scale (mRS) score
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
Time frame: Day 7 post-randomization
Change from baseline in Fugl-Meyer Assessment of Motor Recovery after Stroke motor score at Day 7
Time frame: Day 7 post-randomization
Barthel Index for Activities of Daily Living score at Day 90
Time frame: Day 90 post-randomization
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Utility Index Score at Day 90
Time frame: Day 90 post-randomization
Early neurological deterioration
Time frame: 7 days post-randomisation
Proportion of participants with insomnia
Time frame: Within 7 days after randomization.
Proportion of participants with headache
Time frame: Within 7 days after randomization;
Proportion of participants with symptomatic intracranial hemorrhage
Time frame: Within 7 days after randomization.
All-Cause Mortality
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)
Time frame: Within 90 days post-randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Results publication: PubMed 37314250Ding 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zixiao Li, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LNM-navigated cTBS in people with Ischemic Stroke, run by Beijing Tiantan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lingling Ding, MD (008613552358752, dinglingling@bjtth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients achieving mRS 0-2 (time frame: Day 90 post-randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07645560, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.