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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether low-energy sound waves, known as low-intensity focused ultrasound (LIFU), can alter brain activity and assist with essential tremor (ET), which causes uncontrollable shaking. Researchers aim to determine if LIFU can improve tremors by targeting specific brain areas. The trial seeks individuals with tremors unresponsive to medication who are scheduled for a special ultrasound treatment at UCSF. Participants will have their wrist movements recorded to assess the impact of LIFU. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for essential tremor.

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 prior data suggests that this ultrasound neuromodulation technique is safe for essential tremor?

Research has shown that focused ultrasound, like the kind tested in this trial, is generally safe for treating essential tremor. Several studies have found that MR-guided focused ultrasound (MRgFUS) is well-tolerated. Patients who received MRgFUS for tremors reported quick and lasting improvements, with few serious side effects, indicating the treatment's effectiveness and safety.

These studies suggest that the low-intensity focused ultrasound being tested will also be safe. However, since this trial explores a new use, staying updated on specific safety information from the trial itself is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about focused ultrasound neuromodulation for essential tremor because it offers a non-invasive alternative to traditional treatments like medications and deep brain stimulation. Unlike medication that can have systemic side effects and deep brain surgery that involves significant risks, this technique uses precise sound waves to modulate brain activity without incisions. This approach aims to provide relief from tremors with potentially fewer complications and a quicker recovery time, making it a promising option for patients seeking less invasive treatments.

What evidence suggests that focused ultrasound neuromodulation is effective for essential tremor?

This trial will investigate the use of Focused Ultrasound Neuromodulation for essential tremor. Studies have shown that focused ultrasound can significantly benefit individuals with essential tremor, particularly when other treatments fail. One study found that participants experienced a 73% reduction in tremors five years after treatment. This method uses sound waves to target specific brain areas, helping to calm the tremors. Another study demonstrated that even patients with low skull density, who might not respond well to other treatments, saw improvements. The research suggests that focused ultrasound is a safe and effective way to reduce tremors in people with essential tremor. ^{1 3 6 7 8}

Who Is on the Research Team?

Leo Sugrue, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38306635/

Effectiveness and safety of MR-guided focused ultrasound ... This study suggested that MRgFUS is effective and safe for patients with medication-resistant essential tremor, including those with very low mean SDR.

2. fusfoundation.org fusfoundation.org/posts/focused-ultrasound-for-essential-tremor-five-year-results/

Focused Ultrasound for Essential Tremor: Five-Year Results These participants experienced 73% tremor reduction over baseline at five years post-treatment. Other notable scores remained stable over time, and no new ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1353802025006777

Magnetic resonance-guided focused ultrasound for ... MRgFUS can reduce tremors in ET patients with low skull density ratio (SDR <0.4). · Low SDR patients show lower peak temperatures and smaller ...

4. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2821255

Safety and Efficacy of Staged, Bilateral Focused ... In this open-label trial, 51 patients with essential tremor treated successfully unilaterally underwent focused ultrasound thalamotomy on the opposite side.

5. fusfoundation.org fusfoundation.org/posts/essential-tremor-treatment-continues-to-improve/

Essential Tremor Treatment Continues to Improve FDA Approves First MRI-Guided Focused Ultrasound Device to Treat Essential Tremor July 2016. Researcher News. Focused Ultrasound Foundation.

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000212164

Update on the Long-term Safety of Magnetic Resonance ... MRgFUS treatment results in immediate, significant, long-lasting improvements in tremor, with favorable safety profile.

7. va.gov va.gov/COMMUNITYCARE/docs/providers/CDI/IVC-CDI-00006.pdf

Magnetic Resonance-Guided Focused Ultrasound ... Research evidence and clinical trials support MRgFUS as a safe and effective treatment option for medication-refractory essential tremor.

8. movementdisorders.onlinelibrary.wiley.com movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.30188

Efficacy and Safety of Magnetic Resonance‐Guided Focused ... Magnetic resonance-guided focused ultrasound (MRgFUS) is an established surgical treatment for essential tremor, providing tremor relief ...