Ultrasound Neuromodulation for Essential Tremor

(UNMET Trial)

Overseen By Leo P. Sugrue, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Pacemakers

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to test whether low-intensity focused ultrasound (LIFU) (low energy sound waves) cause temporary changes in brain activity and behavior when directed at particular parts of the brain. By targeting LIFU to the parts of the brain thought to be responsible for essential tremor (ET), and measuring any associated improvement in tremor, the investigators hope to show that LIFU can be a useful tool for studying the brain circuits responsible for tremor and other brain disorders.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Focused Ultrasound Neuromodulation for Essential Tremor?

Research shows that Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is an effective treatment for essential tremor, with studies indicating successful tremor control and positive outcomes at follow-ups up to two years. This treatment is incisionless and targets specific brain areas to reduce tremors, making it a promising option for those who do not respond to medication. ^{1 2 3 4 5}

Is ultrasound neuromodulation safe for treating essential tremor?

Magnetic resonance-guided focused ultrasound (MRgFUS) is generally considered safe for treating essential tremor, with common short-term side effects like dizziness, nausea, and vomiting. Long-term complications such as ataxia (loss of full control of bodily movements) and paresthesias (tingling or numbness) tend to improve over time, making it a promising treatment option with acceptable risks. ^{2 3 6 7 8}

How is the treatment Focused Ultrasound Neuromodulation different from other treatments for essential tremor?

Focused Ultrasound Neuromodulation is unique because it is a non-invasive treatment that uses sound waves to target specific areas in the brain, providing real-time monitoring and avoiding the need for surgery. This approach is particularly beneficial for patients whose tremors do not respond to medication. ^{1 2 4 5 9}

Research Team

Leo Sugrue, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for individuals with essential tremor, a condition causing involuntary shaking. Participants should be able to give informed consent and have no other neurological disorders or serious medical conditions that could interfere with the study.

Inclusion Criteria

I am scheduled for a special ultrasound treatment at UCSF to manage my severe tremor.

Exclusion Criteria

I do not have an MR-conditional pacemaker.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

LIFU Treatment

Participants undergo a single LIFU session lasting 3-4 hours to test the effects of low-intensity focused ultrasound on tremor reduction.

1 day

1 visit (in-person)

HIFU Treatment

Participants proceed with their scheduled HIFU treatment, including wrist-based accelerometer measurements and post-treatment MRI.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in functional connectivity of brain networks.

20-30 minutes

1 visit (in-person)

Treatment Details

Interventions

• Focused Ultrasound Neuromodulation

Trial Overview The study tests low-intensity focused ultrasound (LIFU) on parts of the brain linked to essential tremor. The goal is to see if LIFU can temporarily change brain activity and reduce tremors.

Participant Groups

Group I: To determine the most effective stimulation parameters for DRTT LIFU neuromodulation. Experimental Treatment 2 Interventions

Investigators will record wrist accelerometer signals while participants maintain standardized postures that maximally elicit their tremor before, during, and after delivering LIFU stimulation.

Focused Ultrasound Neuromodulation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as MRgFUS for:

• Essential Tremor

Approved in Canada as MRgFUS for:

• Essential Tremor

Approved in European Union as MRgFUS for:

• Essential Tremor

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Focused Ultrasound Foundation

Collaborator

Trials

18

Recruited

460+

Findings from Research

Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy significantly reduces hand tremors in patients with essential tremor, with a 55% improvement at 6 months and sustained improvements of 56% at 2 years, based on a study of 76 patients.

The procedure is associated with minimal adverse effects, primarily paresthesias and gait disturbances, which did not worsen over the follow-up period, indicating a favorable safety profile with no new complications developing after 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up. Chang, JW., Park, CK., Lipsman, N., et al.[2019]

In a study involving four male patients with essential tremor, bilateral MR-guided focused ultrasound (MRgFUS) treatment resulted in a significant reduction of tremor symptoms, with a decrease in severity of 57.5-69.7% after six months.

No complications were observed in any of the patients, suggesting that simultaneous bilateral thalamotomy using MRgFUS is a safe and effective treatment option for essential tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experience of staged and simultaneous bilateral thalamotomy using MR-guided focused ultrasound in the treatment of essential tremor]. Nabiullina, DI., Galimova, RM., Illarioshkin, SN., et al.[2023]

In a study of 31 patients with Essential Tremor treated with MRgFUS, tremor severity significantly decreased, with an average improvement of 45.5% in the Clinical Rating Scale for Tremor and 62.6% in Hand Tremor Scores after treatment.

The effectiveness of MRgFUS was positively linked to the extent of ablation in the posterior dentatorubrothalamic tract, suggesting that targeting this area may enhance treatment outcomes, while older age was associated with less improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremor suppression following treatment with MRgFUS: skull density ratio consistency and degree of posterior dentatorubrothalamic tract lesioning predicts long-term clinical outcomes in essential tremor. Kyle, K., Maller, J., Barnett, Y., et al.[2023]

In a study of 250 patients with essential tremor, unilateral MRgFUS thalamotomy led to significant and sustained improvement in tremor control, with 73.6% of patients experiencing minimal or no disability after 12 months.

Younger age and higher focal temperature during the procedure were associated with better tremor outcomes, while higher temperatures also correlated with increased balance disturbances, highlighting the need for careful temperature management to optimize safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical and operative factors affecting magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: experience from 250 treatments. Kim, MJ., Park, SH., Chang, KW., et al.[2023]

In a study of 14 patients, MR-guided focused ultrasound (MRgFUS) targeting the anterior-VIM/VOP and posterior subthalamic area significantly reduced essential tremor severity, with a 41.1% improvement in treated arm function over 24 months.

The treatment not only improved tremor scores but also enhanced quality of life, with minimal adverse effects reported, indicating that MRgFUS is a safe and effective option for managing essential tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double lesion MRgFUS treatment of essential tremor targeting the thalamus and posterior sub-thalamic area: preliminary study with two year follow-up. Jameel, A., Gedroyc, W., Nandi, D., et al.[2022]

Magnetic resonance-guided focused ultrasound (MRgFUS) is a safe and effective incisionless treatment for centrally located brain lesions in adolescents and young adults, with no complications reported in a study of 5 patients aged 15-22.

The procedure successfully achieved thermoablation in 4 out of 5 cases, leading to improvements in symptoms such as seizure control, demonstrating its potential therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. Tierney, TS., Alavian, KN., Altman, N., et al.[2022]

Magnetic resonance-guided focused ultrasound (MRgFUS) significantly improves tremor symptoms in patients with essential tremor, with an average improvement of 62.2% in Clinical Rating Scale for Tremor (CRST) scores based on a meta-analysis of 9 studies involving 160 patients.

While MRgFUS has an acceptable complication rate, the most common side effects include dizziness during the procedure and ataxia at 3 months post-treatment, which tends to improve over time, indicating a generally favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis of outcomes and complications of magnetic resonance-guided focused ultrasound in the treatment of essential tremor. Mohammed, N., Patra, D., Nanda, A.[2019]

In a study of 180 treatments using incisionless magnetic resonance-guided focused ultrasound (MRgFUS) for chronic therapy-resistant conditions like Parkinson's disease and essential tremor, the procedure demonstrated high targeting accuracy with a mean 3D accuracy of 0.73 mm and a low side-effect profile, with only 14 documented side effects (7.8% of treatments).

The procedure resulted in slight cognitive improvements measured by the Montreal Cognitive Assessment (MoCA) at 2 days and 1 year post-treatment, indicating potential benefits for cognitive function without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and accuracy of incisionless transcranial MR-guided focused ultrasound functional neurosurgery: single-center experience with 253 targets in 180 treatments. Gallay, MN., Moser, D., Jeanmonod, D.[2023]

Magnetic resonance-guided focused ultrasound thalamotomy provides significant and sustained tremor reduction for patients with medically refractory essential tremor, showing a 43.4% improvement in tremor scores at 2 years compared to baseline.

The study found that the initial lesion volume is significantly associated with the treatment outcome at 1 year, suggesting that larger lesions may lead to better results in tremor reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound thalamotomy for treatment of essential tremor: A 2-year outcome study. Meng, Y., Solomon, B., Boutet, A., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up. [2019]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Experience of staged and simultaneous bilateral thalamotomy using MR-guided focused ultrasound in the treatment of essential tremor]. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Tremor suppression following treatment with MRgFUS: skull density ratio consistency and degree of posterior dentatorubrothalamic tract lesioning predicts long-term clinical outcomes in essential tremor. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Technical and operative factors affecting magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: experience from 250 treatments. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Double lesion MRgFUS treatment of essential tremor targeting the thalamus and posterior sub-thalamic area: preliminary study with two year follow-up. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A meta-analysis of outcomes and complications of magnetic resonance-guided focused ultrasound in the treatment of essential tremor. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Safety and accuracy of incisionless transcranial MR-guided focused ultrasound functional neurosurgery: single-center experience with 253 targets in 180 treatments. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound thalamotomy for treatment of essential tremor: A 2-year outcome study. [2019]