Focused Ultrasound Ablation for Essential Tremor

Overseen By Haiden Berton

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Anticoagulants

Disqualifiers: Hypertension, Coronary artery disease, Dementia, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for essential tremor, a condition that causes shaky hands and arms. Researchers use advanced imaging to enhance a procedure called 3-D Tractography Focused Ultrasound Ablation (Vim-FUSA or Ventral Intermediate Nucleus - Focused Ultrasound Ablation), which targets specific brain areas to reduce tremors. The trial aims to determine if this method is safer and more effective than the current approach. Individuals with moderate to severe essential tremor, whose symptoms have not improved with at least two medications, might be suitable for this study. As an unphased trial, it offers patients the chance to contribute to groundbreaking research that could lead to innovative treatments for essential tremor.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have a stable medication regimen for at least 4 weeks before screening. You may need to temporarily stop any antithrombotic (blood-thinning) medication.

What prior data suggests that this technique is safe for essential tremor patients?

Research shows that focused ultrasound ablation, such as the 3-D tractography Vim-FUSA, is generally well-tolerated. This technique uses sound waves to target and treat brain areas linked to essential tremor. Previous studies found that similar treatments are safe and practical. The FDA approved focused ultrasound for essential tremor in 2016 for other targeting methods, indicating a good safety record. However, research continues to improve the precision and monitoring of the treatment. Patients should consult their doctors to understand the risks and benefits specific to their situation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for essential tremor, which often involve medications like beta-blockers or anticonvulsants, the 3-D Tractography Focused Ultrasound Ablation (FUSA) offers a non-invasive alternative. This technique uses highly focused sound waves to target and disrupt specific brain areas associated with tremors, potentially reducing symptoms without the need for surgery. Researchers are excited because this method allows for precise targeting and may lead to fewer side effects compared to medication or surgical options. Additionally, the use of 3-D tractography enhances the accuracy of the treatment, potentially improving outcomes for patients with essential tremor.

What evidence suggests that 3-D Tractography Vim FUSA is effective for essential tremor?

Research has shown that focused ultrasound targeting the ventral intermediate nucleus (Vim) of the thalamus effectively controls essential tremor. Studies indicate that this method can significantly reduce tremor severity and improve quality of life. In this trial, participants will experience a new technique using 3-D imaging, known as 3-D Tractography Vim FUSA. This technique aims to enhance treatment by providing a clearer view of the brain's nerve pathways, potentially leading to more precise treatment. This increased precision might result in better outcomes compared to standard focused ultrasound methods. Early findings suggest that using MRI scans during the procedure can help predict treatment success. ^{1 2 3 5 6}

Who Is on the Research Team?

Vibhor Krishna, MD SM

Principal Investigator

University of North Carolina at Chapel Hll

Are You a Good Fit for This Trial?

This trial is for individuals with essential tremor, a condition causing involuntary shaking. Participants should be those who haven't responded well to standard treatments. The study excludes people if they have contraindications for magnetic resonance imaging (MRI) or are unable to give informed consent.

Inclusion Criteria

Willing and able to undergo MR imaging

My symptoms did not improve after trying two different medications.

I can attend all required follow-up visits.

Exclusion Criteria

Any significant issue raised by the neurologist or neurosurgeon that may compromise participant safety or potentially interfere with study interpretation

History of drug or alcohol abuse

History of psychosis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Vim FUSA using 3-D tractography, with assessments at baseline and during the surgical procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with tremor assessments at Month 3

3 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 3-D Tractography FUS Ablation

Trial Overview The trial tests an advanced procedure called Vim-FUSA, which uses focused ultrasound ablation guided by 3-D tractography—a technique that maps nerve pathways in the brain—to treat essential tremor. It aims to improve outcomes over standard treatment and includes intraoperative MRI monitoring.

How Is the Trial Designed?

Group I: 3-D Tractography Vim FUSA Experimental Treatment 1 Intervention

Twenty-four consecutive essential tremor (ET) participants undergoing Vim FUSA using 3-D tractography will be assessed at baseline and Month 3.

3-D Tractography FUS Ablation is already approved in United States for the following indications:

Approved in United States as Focused Ultrasound Ablation for:

• Essential Tremor
• Tremor-dominant Parkinson's disease

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Texas Tech University Health Sciences Center, El Paso

Collaborator

Trials

51

Recruited

5,800+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

MRI-guided focused ultrasound (MRgFUS) can initially improve essential tremor (ET) symptoms, but tremor recurrence is common within 6 months, highlighting the need for precise targeting during the procedure.

In a case study, the MRgFUS lesion was found to be significantly smaller and less effective than the volume of activated tissue from deep brain stimulation (DBS), suggesting that better targeting of the corticothalamic tract may enhance long-term tremor relief in ET patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report on Deep Brain Stimulation Rescue After Suboptimal MR-Guided Focused Ultrasound Thalamotomy for Essential Tremor: A Tractography-Based Investigation. Saluja, S., Barbosa, DAN., Parker, JJ., et al.[2020]

In a study of 35 Japanese patients with disabling essential tremor, unilateral focused ultrasound (FUS) thalamotomy resulted in a significant 56.4% reduction in tremor severity after 12 months, demonstrating its efficacy in treating this condition.

The procedure had an excellent safety profile, with no severe adverse events reported, and the most common side effect, gait disturbance, resolved in all cases, indicating that FUS thalamotomy is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Thalamotomy for Refractory Essential Tremor: A Japanese Multicenter Single-Arm Study. Abe, K., Horisawa, S., Yamaguchi, T., et al.[2021]

Advanced imaging techniques like MR diffusion tractography show promise for accurately targeting the thalamic ventral intermediate nucleus (VIM) for tremor treatment, which is crucial for procedures like deep brain stimulation (DBS) and MR-guided focused ultrasound (MRgFUS).

The review highlights a novel 3-tract technique that improves VIM localization by illustrating the relationship of key white matter tracts, potentially enhancing treatment outcomes by allowing for more precise targeting in patients with varying thalamic anatomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI and tractography techniques to localize the ventral intermediate nucleus and dentatorubrothalamic tract for deep brain stimulation and MR-guided focused ultrasound: a narrative review and update. Lehman, VT., Lee, KH., Klassen, BT., et al.[2021]

In a study of 30 patients with essential tremor, MRgFUS thalamotomy led to significant recovery in functional brain activity related to tremor control, with improvements observed at 6 months post-treatment.

Changes in brain connectivity and activity were correlated with tremor relief, suggesting that preoperative functional connectivity could serve as a biomarker to predict how well patients will respond to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the impact of MR-guided focused ultrasound thalamotomy on brain activity and connectivity in patients with essential tremor. Lu, H., Lin, J., Xiong, Y., et al.[2023]

Magnetic resonance-guided focused ultrasound (MRgFUS) effectively reduced tremor severity in 21 patients with essential tremor, indicating its potential as a safe and incisionless treatment option.

Six months post-treatment, there was a notable increase in functional connectivity within the tremor network, suggesting that MRgFUS not only impacts the cerebellar network but also involves areas related to visual processing, highlighting the complexity of tremor-related brain activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRgFUS of the nucleus ventralis intermedius in essential tremor modulates functional connectivity within the classical tremor network and beyond. Kindler, C., Upadhyay, N., Purrer, V., et al.[2023]

In a study of 16 patients with drug-resistant essential tremor, 13 showed significant improvement after treatment with Magnetic-Resonance-guided Focused-Ultrasound (MRgFUS) targeting the thalamic ventralis-intermediate nucleus, indicating its efficacy as a treatment option.

Post-treatment assessments revealed that cortico-muscular coherence (CMC) increased in the motor areas of the treated hemisphere immediately after MRgFUS, suggesting that the treatment leads to enhanced communication in the brain regions responsible for motor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-guided focused-ultrasound thalamotomy in essential tremor: Immediate and delayed changes in cortico-muscular coherence and cortico-cortical out-strength. Visani, E., Panzica, F., Eleopra, R., et al.[2023]

Intraoperative restricted diffusion imaging (RDI) effectively identifies the volume and location of focused ultrasound lesions, which is crucial for predicting clinical outcomes in patients undergoing treatment for essential tremor.

Lesions located at the ventral border of the ventral intermediate nucleus were linked to significant improvement in tremor symptoms post-surgery, while lesions extending into the inferolateral white matter were associated with postoperative ataxia, highlighting the importance of precise lesion targeting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative lesion characterization after focused ultrasound thalamotomy. Sammartino, F., Yeh, FC., Krishna, V.[2021]

In a study involving 6 patients with essential tremor, unilateral MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract resulted in an impressive 83% reduction in hand tremor scores after 6 months, indicating high efficacy for this treatment.

Quality of life improved by 52% following the procedure, and while there were mild and transient side effects like hand clumsiness and gait instability, fine motor function and dexterity remained unaffected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unilateral cerebellothalamic tract ablation in essential tremor by MRI-guided focused ultrasound. Schreglmann, SR., Bauer, R., Hägele-Link, S., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06331052

3-D Tractography FUS Ablation for Essential Tremor 3-D tractography Vim-FUSA will improve the Vim ablation compared to standard Vim-FUSA and prove safe and feasible in the clinical setting.

2. reporter.nih.gov reporter.nih.gov/project-details/10344274

3-D Tractography Focused Ultrasound Ablation for ... In the interventional human study, we will evaluate the utility of i-MR in predicting Vim-FUSA clinical outcomes. Public Health Relevance Statement. PROJECT ...

3. trialx.com trialx.com/clinical-trials/listings/287734/3-d-tractography-fus-ablation-for-essential-tremor/

3-D Tractography FUS Ablation for Essential Tremor The investigators hypothesize that 3-D tractography Vim-FUSA will improve the Vim ablation compared to standard Vim-FUSA and prove safe and ...

4. fusfoundation.org fusfoundation.org/diseases-and-conditions/essential-tremor/

Essential Tremor Learn how focused ultrasound could transform the quality of life and decrease the cost of care for patients with Essential Tremor.

5. thejns.org thejns.org/focus/view/journals/neurosurg-focus/57/3/article-pE3.xml

Brain targeting for focused ultrasound essential tremor ... The ventral intermediate nucleus of the thalamus (Vim) is the target of choice for tremor control in MRgFUS, DBS, Gamma Knife radiosurgery, and radiofrequency ...

6. reporter.nih.gov reporter.nih.gov/project-details/10650282

3-D Tractography Focused Ultrasound Ablation for Essential ... We hypothesize that 3-D tractography Vim-FUSA will improve the Vim ablation compared to standard Vim-FUSA and prove safe and feasible in the clinical setting.