Safety, Dose-Finding, and Efficacy of Transcranial Pulse Stimulation for Post-Stroke Neurorehabilitation

This is a prospective, interventional, non-randomized, open-label dose-finding study evaluating the safety, tolerability, and preliminary efficacy of transcranial pulse stimulation (TPS) in patients with ischemic stroke.

Participants will receive TPS using the NEUROLITH® TPS system (Storz Medical AG, Switzerland). The study will use a sequential dose-escalation design with three energy levels: 0.15, 0.20, and 0.25 mJ/mm². Each participant will receive TPS three times per week for 2 weeks, for a total of 6 treatment sessions. Each session will deliver 4,000 pulses at a frequency of 4 Hz.

The primary focus of the study is to evaluate the safety and tolerability of different TPS energy levels. Secondary and exploratory assessments will evaluate changes in motor function, balance, activities of daily living, quality of life, and neurophysiological measures. Electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) will be used to assess changes in brain activity associated with treatment.

The study plans to enroll 9 participants initially, with 3 participants assigned to each dose level. Dose escalation will proceed after safety evaluation of the preceding dose level. If the predefined safety criteria are met, the study may be expanded to include additional participants.

• Required Field (Device): Participants will receive transcranial pulse stimulation (TPS) using the NEUROLITH® TPS system (Storz Medical AG, Switzerland). TPS will be administered at the assigned energy level of 0.15, 0.20, or 0.25 mJ/mm², at a frequency of 4 Hz, with 4,000 pulses per session. Treatment will be administered three times per week for 2 weeks, for a total of 6 treatment sessions. Dose escalation will proceed sequentially after safety evaluation of the preceding dose level.

Primary outcomes

• Incidence of Dose-Limiting Toxicity (DLT) and Adverse Events [Baseline, 2 weeks (immediately post-treatment), and 1 month post-treatment]: Safety monitoring including adverse events (AEs), serious adverse events (SAEs), and DLT defined as: NIHSS increase ≥4 points lasting ≥24-48 hours, new-onset seizure, new or worsening neurological deficits, intolerable persistent AEs (headache, dizziness, nausea), or acute MRI worsening (new DWI stroke, hemorrhage, or severe edema).

Sex: All, accepts healthy volunteers

1. Age 20-80 years old.
2. Confirmed ischemic stroke verified by MRI.
3. Stroke onset between 1 month and 6 months prior to study enrollment.
4. NIHSS score of 4-25 points, with quantifiable motor or language deficits.
5. Completed acute medical care with stable vital signs.

• Director, Department of Physical Medicine and Rehabilitation,, Study director, Taipei Hospital, Ministry of Health and Welfare