Individual Alpha Frequency-Based rTMS for Post-Stroke Motor Recovery: Efficacy and Neurophysiological Mechanisms

Overview

The goal of this clinical trial is to evaluate the efficacy of a personalized brain stimulation technique, Individual Alpha Frequency (IAF)-based rTMS, for motor function recovery in adult patients with a first-ever ischemic stroke. The main questions it aims to answer are: 1. Does IAF-based rTMS improve upper and lower limb motor recovery better than a sham (placebo) stimulation? 2. How does this personalized stimulation affect brain wave activity (cortical oscillatory dynamics) as measured by EEG? Researchers will compare active IAF-based rTMS with a sham stimulation control in a crossover design to see if the active treatment leads to better clinical motor outcomes and beneficial changes in brain activity. Participants will: 1. Be randomly assigned to one of two sequences: receiving two weeks of active IAF-rTMS followed by two weeks of sham stimulation, or vice versa. 2. Attend 30-minute brain stimulation sessions, targeted at the motor cortex, 5 days a week for a total of 4 weeks. 3. Undergo clinical motor function assessments (including NIHSS, FMA-UE, and FMA-LE) and EEG recordings at three time points: at baseline, after 2 weeks, and at the end of the 4-week study.

Interventions

• Device Active Individual Alpha Frequency-based Repetitive Transcranial Magnetic Stimulation (IAF-rTMS)
  Participants will receive Individual Alpha Frequency (IAF)-guided repetitive transcranial magnetic stimulation (rTMS) targeted at the ipsilesional primary motor cortex (M1). The stimulation frequency will be tailored to each participant's intrinsic IAF (ranging from 8 to 12 Hz). If the ipsilesional IAF is not available, the contralesional alpha frequency will be utilized. The stimulation intensity is set at 100% of the resting motor threshold (RMT). The protocol consists of a 2.5-second train du
• Device Sham Individual Alpha Frequency-based Repetitive Transcranial Magnetic Stimulation (IAF-rTMS)
  Participants will receive sham rTMS using the identical device and stimulation parameters (100% RMT intensity, 2.5-second train, 10-second interval, 30-minute session duration) targeted at the same anatomical site (ipsilesional M1). To achieve the sham condition, the stimulation coil will be tilted at a 90-degree angle (one-wing 90° method) away from the scalp. This specific coil placement produces the same acoustic click and similar somatic sensations as the active treatment, while preventing t

Primary outcome measures

• National Institutes of Health Stroke Scale(NIHSS) [Time frame: Baseline, end of Week 2, and end of Week 4]
• Fugl-Meyer Assessment-Upper Extremity(FMA-UE) [Time frame: Baseline, end of Week 2, and end of Week 4]
• Fugl-Meyer Assessment-Lower Extremity(FMA-LE) [Time frame: Baseline, end of Week 2, and end of Week 4]

Secondary outcome measures (4)

• Electroencephalography [Time frame: Baseline, end of Week 2, and end of Week 4]
• Modified Rankin Scale(mRS) [Time frame: Baseline, end of Week 2, and end of Week 4]
• Modified Ashworth Scale(MAS) [Time frame: Baseline, end of Week 2, and end of Week 4]
• EQ-5D quality of life questionnaire [Time frame: Baseline, end of Week 2, and end of Week 4]

Eligibility criteria

Inclusion criteria

• Age >18
• First ischemic stroke patient, confirmed by brain MRI
• Has not received repetitive transcranial magnetic stimulation (rTMS) treatment after this stroke episode
• Cortical, subcortical infarction with motor impairment
• Baseline ADL intact (Full score of pre-stroke Barthel Index)
• Clear consciousness and with the ability to understand and cooperate with the study
• NIHSS 5-20, or FMA-UE 20-50, or FMA-LE 15-25
• Within 2 to 12 weeks after stroke onset
• Participants had received stable treatment prior to the trial or were evaluated by a physician as having an inadequate response to conventional rehabilitation therapy

Exclusion criteria

• Hemorrhagic transformation in the brain
• Unstable condition
• Stroke primarily caused by cancer-related hypercoagulability or autoimmune diseases (e.g., systemic lupus erythematosus, antiphospholipid syndrome)
• Known previous peripheral nerve injury or peripheral neuropathy on the affected side that impairs mobility
• Individual history of epilepsy
• Presence of cardiac pacemakers, cochlear implants, drug delivery pumps, implantable cardioverter-defibrillators, implanted neurostimulators, or other metal objects in the body. This also includes patients who have undergone cranioplasty or have other implanted devices incompatible with rTMS
• Pregnancy
• Multiple sclerosis patient
• Use of tricyclic antidepressants or other medications that may lower the seizure threshold
• Severe alcoholism
• Hamilton Depression Rating Scale suicide item score ≥ 2
• Patients with skin lesions or damage at the intended site of stimulation.
• Family history of epilepsy
• Patients with brain injuries that may affect the seizure threshold
• Patients who develop sleep disorders during the course of rTMS treatment
• Patients currently using anti-epileptic drugs
• Patients with severe heart disease or patients with uncontrolled migraines caused by increased intracranial pressure

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• Department of neurology, National Taiwan Univeristy Hospital Yunlin branch — Douliu

Identifiers

NCT: NCT07498777 · 202510112DINC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗