Focused Ultrasound Ablation for Essential Tremor

Overseen By Vibhor Krishna, MD, SM

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

Trial Summary

What is the purpose of this trial?

The investigators propose to advance Vim-FUSA (Ventral Intermediate Nucleus - Focused Ultrasound Ablation) with the support of 3-D tractography, a neuroimaging technique to visually represent nerve tracts within the brain. The investigators 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. The investigators also hypothesize that intraoperative magnetic resonance (i-MR) monitoring will differentiate ablated tissue from immediate perilesional edema and accurately predict the Vim-FUSA clinical outcomes.

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 data supports the effectiveness of the treatment 3-D Tractography FUS Ablation for Essential Tremor?

Several studies have shown that focused ultrasound ablation (FUSA) of the ventral intermediate nucleus in the brain can be effective for treating essential tremor, with safety and efficacy demonstrated in feasibility studies and a randomized, controlled trial. However, the outcomes can vary, and precise targeting is crucial for the treatment's success. ^{1 2 3 4 5}

Is focused ultrasound ablation safe for humans?

Several studies, including a multicenter trial, have shown that focused ultrasound ablation is generally safe for treating essential tremor, with safety demonstrated in feasibility studies and clinical trials. ^{1 3 4 6 7}

How is the 3-D Tractography FUS Ablation treatment different from other treatments for essential tremor?

The 3-D Tractography FUS Ablation is unique because it uses focused ultrasound waves to create precise lesions in the brain without any incisions, targeting the ventral intermediate nucleus to treat essential tremor. This non-invasive approach is guided by MRI and aims to modulate specific brain pathways, potentially offering a less invasive alternative to traditional surgical methods like deep brain stimulation. ^{1 2 3 5 8}

Research Team

Vibhor Krishna, MD SM

Principal Investigator

University of North Carolina at Chapel Hll

Eligibility Criteria

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

My symptoms did not improve after trying two different medications.

Willing and able to undergo MR imaging

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

References

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

Intraoperative lesion characterization after focused ultrasound thalamotomy. [2021]

2. Switzerland 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. [2020]

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

Focused Ultrasound Thalamotomy for Refractory Essential Tremor: A Japanese Multicenter Single-Arm Study. [2021]

4. United States 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. [2021]

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

MRgFUS of the nucleus ventralis intermedius in essential tremor modulates functional connectivity within the classical tremor network and beyond. [2023]

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

Assessing the impact of MR-guided focused ultrasound thalamotomy on brain activity and connectivity in patients with essential tremor. [2023]

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

Unilateral cerebellothalamic tract ablation in essential tremor by MRI-guided focused ultrasound. [2022]

8. Netherlands 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. [2023]