Neuromodulation Effect of Focused Ultrasound for Motor Recovery in Patients With Stroke

Transcranial focused ultrasound (tFUS) can be used as a non-invasive brain neuromodulation technique. Low-intensity focused ultrasound has been demonstrated to be safe and have neuromodulatory effects on the cerebral cortex in healthy human and animal experiments.This study aims to investigate the effect of tFUS on cortical excitability for motor recovery in patients with stroke.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Focused Ultrasound
• Intervention / Treatment: Device: NaviFUS® Neuronavigation-guided focused ultrasound system; Device: NaviFUS® Neuronavigation-guided focused ultrasound system

Detailed Description

The study is a pilot study for feasibility, which aims to recruit 20 patients with subacute (within 3 months) stroke and unilateral hemiparesis. tFUS stimulation will be delivered to the primary motor cortex on the healthy side. The treatment protocol consists of once daily treatment for consecutive five tFUS sessions. The primary outcomes are defined as cortical excitability assessment in bilateral primary motor cortex, as well as safety analysis; the secondary outcome measures include the Fugl-Meyer Assessment, Medical Research Council score, National Institutes of Health Stroke Scale (NIHSS), Barthel Index, Modified Rankin Scale and functional brain activities. The evaluation will be conducted before treatment and on the first day, first week, fourth week, and twelfth week after completing tFUS.

The second part of this study is an efficacy investigation, which plans to recruit 30 subacute stroke patients for a randomized controlled trial with a parallel-group design. The experimental group will receive focused ultrasound stimulation with the same parameters and target site as the Phase I pilot study, while the control group will receive sham stimulation at the same location. The treatment frequency will be the same as that of the pilot study.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Meng Ting Lin, M.D.; Phone Number: 67048 +886-2312-3456; Email: b96401093@ntu.edu.tw
• Study Contact Backup: Name: Ming Yen Hsiao, M.D.; Phone Number: 67651 +886-2312-3456; Email: myferrant@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Meng Ting Lin, M.D.; Phone Number: 67048 +886-2312-3456; Email: mntinglin@ntuh.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with stroke (including hemorrhagic or ischemic stroke) diagnosed by a board-certificated physician.
• Occurrence of stroke within three months.
• Upper limb muscle strength ≤ 4 points according to the Medical Research Council Manual Muscle Testing scale.
• No previous history of stroke, epilepsy, dementia, Parkinson's disease, or other neurodegenerative diseases.
• Patients could maintain sitting posture for more than 15 minutes on a chair.
• 18 years of age or older.

Exclusion Criteria:

• History of recurrent stroke, traumatic brain injuries, brain tumors, spinal cord injury, Parkinson's disease or other musculoskeletal system diseases that may affect evaluation and treatment.
• Contraindications to focused ultrasound, including pregnancy, cardiac pacemaker or implantable medical device, abnormal connective tissue diseases, coagulopathy (PLT<100,000/μL, PT>14 seconds, APTT>36 seconds, INR>1.3), implants near or in the brain, or those deemed Unsuitable for this treatment by the physician.
• Unable to cooperate with treatment or functional assessment due to impaired consciousness or aphasia; inability to informed consent.
• Patient with cranial bone factor causing the inability of tFUS penetration.
• Patient under anticoagulants with coagulopathy (PLT<100,000/μL, PT>14 seconds, APTT>36 seconds, INR>1.3)
• Patients who are not suitable for undergoing CT imaging examination;
• Major physical illnesses and neurological disorders (such as epilepsy, brain surgery, etc.)
• Patients with metallic implants in their bodies;
• Patients taking tricyclic antidepressants, analgesics, or using antiepileptic drugs
• Individuals experiencing sleep disorders during tFUS treatment;
• Individuals with history of alcoholism
• Patients with severe or uncontrollable intracranial pressure;
• Patients requiring anticoagulants;
• Any intracranial space-occupying lesions;
• Significant calcification of intracranial vessels based on pre-treatment CT imaging;
• Subjects with lesions/wounds on the scalp in the target region.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment with tFUS	Device: NaviFUS® Neuronavigation-guided focused ultrasound system; The treatment protocol consists of once daily treatment for consecutive five tFUS sessions.; Device: NaviFUS® Neuronavigation-guided focused ultrasound system; No ultrasound energy will be delivered (Mechanical Index, MI = 0); only the background music will be played (During each treatment session, the background music will be presented in the same way as in the experimental group during the operation of the focused ultrasound system). All other stimulation settings and procedures will be identical to those used in the experimental group
Sham Comparator: Control; No ultrasound energy, only the background music will be played.	Device: NaviFUS® Neuronavigation-guided focused ultrasound system; The treatment protocol consists of once daily treatment for consecutive five tFUS sessions.; Device: NaviFUS® Neuronavigation-guided focused ultrasound system; No ultrasound energy will be delivered (Mechanical Index, MI = 0); only the background music will be played (During each treatment session, the background music will be presented in the same way as in the experimental group during the operation of the focused ultrasound system). All other stimulation settings and procedures will be identical to those used in the experimental group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical excitability	The amplitude and latency of maximal MEP, rMT in bilateral primary motor cortex will be assessed.	Before treatment and on the first day (equal to day 6), first week (equal to day 12), fourth week (equal to day 33), and twelfth week (equal to day 89) after completing consecutive five tFUS sessions.
Incidence of Treatment-related Adverse Events	Includes rate of minor (scalp pain, headache, short-term dizziness, nausea, vomiting, short-term weakness, short-term numbness) and severe adverse events (seizure, persistent new onset weakness, documented new intracranial hemorrhage or infarction, death)	Before treatment and on the first day (equal to day 6), first week (equal to day 12), fourth week (equal to day 33), and twelfth week (equal to day 89) after completing consecutive five tFUS sessions.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medical Research Council score	The Medical Research Council (MRC) score is a simple and widely used scale to assess muscle strength. It rates muscle strength on a scale from 0 to 5, with 0 being no muscle contraction and 5 being normal muscle strength.	Before treatment and on the first day (equal to day 6), first week (equal to day 12), fourth week (equal to day 33), and twelfth week (equal to day 89) after completing consecutive five tFUS sessions.
National Institutes of Health Stroke Scale (NIHSS)	The National Institutes of Health Stroke Scale (NIHSS) is a standardized tool used to assess the severity of a stroke and its effects on patients. It evaluates various neurological functions, such as consciousness, movement, sensation, and language, assigning scores ranging from 0 to 42, with higher scores indicating more severe stroke symptoms.	Before treatment and on the first day (equal to day 6), first week (equal to day 12), fourth week (equal to day 33), and twelfth week (equal to day 89) after completing consecutive five tFUS sessions.
Barthel Index	The Barthel Index is a measure of a person's ability to perform activities of daily living. It assesses functions such as feeding, bathing, grooming, dressing, bowel and bladder control, toileting, transfers, mobility, and stairs. The score ranges from 0 to 100, with higher scores indicating greater independence.	Before treatment and on the first day (equal to day 6), first week (equal to day 12), fourth week (equal to day 33), and twelfth week (equal to day 89) after completing consecutive five tFUS sessions.
Modified Rankin Scale	The Modified Rankin Scale is a widely used tool to assess a patient's level of disability after a stroke or other neurological disorders. It measures the degree of disability or dependence in daily activities, with scores ranging from 0 (no symptoms) to 6 (death).	Before treatment and on the first day (equal to day 6), first week (equal to day 12), fourth week (equal to day 33), and twelfth week (equal to day 89) after completing consecutive five tFUS sessions.
Functional brain activities	Functional brain activities were detected by fNIRS (NIRSport2 NIRx Medical Technologies LLC, Glen Head, NY, USA). The subjects were requested to perform functional task (unilateral hand grasping), and brain activities was recorded by fNIRS in the following brain regions: bilateral premotor cortices, supplementary motor area, M1 and primary somatosensory cortices. The ΔHbO2 signal will be analyzed using the HOMER2 fNIRS analysis software.	Before treatment and on the first day (equal to day 6), first week (equal to day 12), fourth week (equal to day 33), and twelfth week (equal to day 89) after completing consecutive five tFUS sessions.
Fugl-Meyer Assessment-Upper Extremity	The Fugl-Meyer Assessment for upper extremity is a standardized tool used to assess motor recovery after stroke. It consists of four items: shoulder/elbow/forearm, wrist, hand, and coordination. Each item is scored individually, with scores ranging from 0 to 2 depending on the quality of the movement. The total score ranges from 0 to 66, with higher scores indicating better motor function and recovery.	Before treatment and on the first day (equal to day 6), first week (equal to day 12), fourth week (equal to day 33), and twelfth week (equal to day 89) after completing consecutive five tFUS sessions.

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Meng Ting Lin, M.D., National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: 202305124DIPB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No