A Phase 2b Trial of Lesion Network Mapping-Guided cTBS for Motor Recovery After Acute Ischemic Stroke

NCT07645560 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: KY2025-087
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Stroke

Keywords

ishchemic stroke; Lesion network mapping; Continuous theta-burst stimulation; Motor function; Neuronavigation

Outcome Measures

Primary Outcomes (2)

• Proportion of patients achieving mRS 0-2

  Day 90 post-randomization

• Proportion experiencing serious adverse events (SAEs)

  Proportion experiencing serious adverse events (SAEs), including seizures

  Within 90 days post-randomization

Secondary Outcomes (13)

• Distribution shift in mRS scores

  Day 90 post-randomization

• Proportion of patients achieving mRS 0-1

  Day 90 post-randomization

• National Institutes of Health Stroke Scale (NIHSS) total score

  Day 7 post-randomization

• Fugl-Meyer Assessment (FMA) score

  Day 7 post-randomization

• Barthel Index of Activities of Daily Living score

  Day 90 post-randomization

Study Arms (2)

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.

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.

Device: Sham cTBS

Interventions

LNM-navigated cTBS DEVICE

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.

LNM-navigated cTBS group

Sham cTBS DEVICE

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.

Sham cTBS group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, 100070, China

Location

Related Publications (1)

• 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 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Lingling Ding, MD

CONTACT

008613552358752; dinglingling@bjtth.org

Zixiao Li, MD

CONTACT

lizixiao2008@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending physician

Study Record Dates

• First Submitted: June 9, 2026
• First Posted: June 12, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)