Low-intensity focused ultrasound targeting a deep brain nucleus to reduce refractory hand tremor.

Modulate Tremor Severity With Low-intensity Focused Ultrasound Stimulation Targeting the Deep Nucleus of Patients With Refractory Hand Tremor.

This study will try low-intensity NaviFUS-ctbTUS focused ultrasound to see if it reduces hand tremor in adults with Parkinson's disease, essential tremor, or dystonic tremor that have not improved with medication.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: National Taiwan University Hospital (other)
• Locations: 1 site (Hsinchu, Hsinchu City)
• Trial ID: NCT07172295 on ClinicalTrials.gov

What this trial studies

Twelve adults with medication-refractory Parkinsonian, essential, or dystonic hand tremor will receive accelerated NaviFUS-ctbTUS low-intensity focused ultrasound targeting a deep brain nucleus. Treatments will be delivered at National Taiwan University Hospital Hsin-Chu Branch with tremor severity recorded before and after stimulation to document any change. Participants must be MRI-eligible, agree to shave hair over the treatment area, and maintain stable medications and normal liver and kidney function. Safety monitoring and follow-up visits will be performed at the study site.

Who should consider this trial

Good fit: Adults aged 18–80 with Parkinsonian, essential, or dystonic hand tremor that has an inadequate response to medication, who are MRI-compatible, willing to shave hair over the treatment area, on a stable medication regimen, and with normal liver and renal tests.

Not a fit: Patients with intracranial implants unsuitable for MRI, unstable medications, abnormal liver or kidney tests, pregnant people, or those outside the 18–80 age range are unlikely to be eligible or receive benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could reduce tremor severity and improve hand function for people whose tremor does not respond to medication.

How similar studies have performed: High-intensity focused ultrasound has shown benefit for tremor in prior trials, but low-intensity NaviFUS-ctbTUS neuromodulation of deep nuclei is a newer, less-tested approach.

Eligibility criteria

Inclusion Criteria:

* Age between 18 and 80 years.
* Subjects must belong to one of the following three categories:

  1. Patients with Parkinson's disease tremor who have an inadequate response to medication.
  2. Patients with essential tremor who have an inadequate response to medication.
  3. Patients with dystonic tremor who have an inadequate response to medication.
* Subjects are willing to shave hair over the treatment area for focused ultrasound.
* Stable medication regimen (types and dosages) for at least 4 weeks prior to study enrollment.
* Normal liver and renal function (Creatinine \< 1.3 mg/dL, GPT \< 41 U/L).
* Female participants of childbearing potential, or male participants with female partners of childbearing potential, must agree to use appropriate contraception from the first study treatment until at least 6 months after the last treatment to prevent pregnancy.

Exclusion Criteria:

* Presence of intracranial implants deemed unsuitable for MRI, such as metal clips, ventriculoperitoneal (VP) shunts, cochlear implants, deep brain stimulation (DBS) devices, pacemakers, or implantable cardioverter- defibrillators (ICDs).
* Any abnormalities along the focused ultrasound beam path through the skull, including scars on the skull, scalp conditions (e.g., eczema), open wounds, calp atrophy, or significant calcification confirmed by imaging along the ultrasound transmission pathway.
* Pregnant or breastfeeding women.
* Use of investigational drugs from other clinical trials.
* Patients with major depressive disorder (Beck Depression Inventory-II score \> 30 within the past year) or with suicidal ideation.
* Any condition that, in the opinion of the investigator, may interfere with treatment efficacy or increase risk to the subject.
* Presence of any brain tumors, vascular malformations, or significant traumatic brain injury.
* Presence of significant psychiatric symptoms (Clinical Dementia Rating \[CDR\]

  * 2).
* Use of anticoagulant medications.
* Use of medications known to exacerbate tremor.
* Tremor due to metabolic or psychogenic causes.
* Coagulopathy or abnormal coagulation profiles, including any of the following:

  1. Platelet count ≤ 100,000/µL
  2. INR ≥ 1.5
  3. PT ≥ 1.5 × upper limit of normal (ULN)
  4. aPTT ≥ 1.5 × ULN
  5. Fibrinogen ≤ 150 mg/dL
* Inability to provide informed consent or comply with study procedures, posing potential safety concerns.
* Insufficient skull density as determined by pre-treatment evaluation, resulting in ultrasound transmission efficiency less than 20%.

Where this trial is running

Hsinchu, Hsinchu City

• National Taiwan University Hospital Hsin-Chu Branch — Hsinchu, Hsinchu City, Taiwan (RECRUITING)

Study contacts

• Study coordinator: Kai-Hsiang Kai-Hsiang, M.D.

Conditions: Parkinson Disease, Essential Tremor, Dystonic Tremor, Continuous Theta Burst Stimulation Transcranial Focused Ultrasound, NaviFUS, Tremor, Transcranial focused ultrasound