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

Overview

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.

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.

Interventions

• 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

Primary outcome measures

• Incidence of Treatment-related Adverse Events [Time frame: 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.]
• Cortical excitability [Time frame: 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 (6)

• Fugl-Meyer Assessment-Upper Extremity [Time frame: 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.]
• Medical Research Council score [Time frame: 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) [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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.]

Eligibility criteria

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.

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

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• National Taiwan University Hospital — Taipei

Identifiers

NCT: NCT06391086 · 202305124DIPB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗