Focused Ultrasound Ablation for Essential Tremor
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of North Carolina, Chapel Hill
Must not be taking: Anticoagulants
Disqualifiers: Hypertension, Coronary artery disease, Dementia, others
No Placebo Group
Approved in 1 jurisdiction
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.
12345Is 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.
13467How 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.
12358Eligibility 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.
+2 more
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
+12 more
Trial 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)
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: 3-D Tractography Vim FUSAExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of North Carolina at Chapel HillChapel Hill, NC
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Who Is Running the Clinical Trial?
University of North Carolina, Chapel HillLead Sponsor
University of PittsburghCollaborator
Texas Tech University Health Sciences Center, El PasoCollaborator
National Institute of Neurological Disorders and Stroke (NINDS)Collaborator
References
Intraoperative lesion characterization after focused ultrasound thalamotomy. [2021]Outcomes after focused ultrasound ablation (FUSA) for essential tremor remain heterogeneous, despite therapeutic promise. Clinical outcomes are directly related to the volume and location of the therapeutic lesions, consistent with CNS ablative therapies. Recent data demonstrate that postoperative diffusion MRI, specifically the quantification of intracellular diffusion by restricted diffusion imaging (RDI), can accurately characterize focused ultrasound lesions. However, it is unclear whether RDI can reliably detect focused ultrasound lesions intraoperatively (i.e., within a few minutes of lesioning) and whether the intraoperative lesions predict delayed clinical outcomes.
Case Report on Deep Brain Stimulation Rescue After Suboptimal MR-Guided Focused Ultrasound Thalamotomy for Essential Tremor: A Tractography-Based Investigation. [2020]Essential tremor (ET) is the most prevalent movement disorder in adults, and can often be medically refractory, requiring surgical intervention. MRI-guided focused ultrasound (MRgFUS) is a less invasive procedure that uses ultrasonic waves to induce lesions in the ventralis intermedius nucleus (VIM) to treat refractory ET. As with all procedures for treating ET, optimal targeting during MRgFUS is essential for efficacy and durability. Various studies have reported cases of tremor recurrence following MRgFUS and long-term outcome data is limited to 3-4 years. We present a tractography-based investigation on a case of DBS rescue for medically refractory ET that was treated with MRgFUS that was interrupted due to the development of dysarthria during the procedure. After initial improvement, her hand tremor started to recur within 6 months after treatment, and bilateral DBS was performed targeting the VIM 24 months after MRgFUS. DBS induced long-term tremor control with monopolar stimulation. Diffusion MRI tractography was used to reconstruct the dentatorubrothalamic (DRTT) and corticothalmic (CTT) tracts being modulated by the procedures to understand the variability in efficacy between MRgFUS and DBS in treating ET in our patient. By comparing the MRgFUS lesion and DBS volume of activated tissue (VAT), we found that the MRgFUS lesion was located ventromedially to the VAT, and was less than 10% of the size of the VAT. While the lesion encompassed the same proportion of DRTT streamlines, it encompassed fewer CTT streamlines than the VAT. Our findings indicate the need for further investigation of targeting the CTT when using neuromodulatory procedures to treat refractory ET for more permanent tremor relief.
Focused Ultrasound Thalamotomy for Refractory Essential Tremor: A Japanese Multicenter Single-Arm Study. [2021]Several feasibility studies and a randomized, controlled, multicenter trial have demonstrated the safety and efficacy of unilateral transcranial magnetic resonance-guided focused ultrasound (FUS) lesioning of the ventral intermediate thalamic nucleus in treating essential tremor.
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]The thalamic ventral intermediate nucleus (VIM) can be targeted for treatment of tremor by several procedures, including deep brain stimulation (DBS) and, more recently, MR-guided focused ultrasound (MRgFUS). To date, such targeting has relied predominantly on coordinate-based or atlas-based techniques rather than directly targeting the VIM based on imaging features. While general regional differences of features within the thalamus and some related white matter tracts can be distinguished with conventional imaging techniques, internal nuclei such as the VIM are not discretely visualized. Advanced imaging methods such as quantitative susceptibility mapping (QSM) and fast gray matter acquisition T1 inversion recovery (FGATIR) MRI and high-field MRI pulse sequences that improve the ability to image the VIM region are emerging but have not yet been shown to have reliability and accuracy to serve as the primary method of VIM targeting. Currently, the most promising imaging approach to directly identify the VIM region for clinical purposes is MR diffusion tractography.In this review and update, the capabilities and limitations of conventional and emerging advanced methods for evaluation of internal thalamic anatomy are briefly reviewed. The basic principles of tractography most relevant to VIM targeting are provided for familiarization. Next, the key literature to date addressing applications of DTI and tractography for DBS and MRgFUS is summarized, emphasizing use of direct targeting. This literature includes 1-tract (dentatorubrothalamic tract [DRT]), 2-tract (pyramidal and somatosensory), and 3-tract (DRT, pyramidal, and somatosensory) approaches to VIM region localization through tractography.The authors introduce a 3-tract technique used at their institution, illustrating the oblique curved course of the DRT within the inferior thalamus as well as the orientation and relationship of the white matter tracts in the axial plane. The utility of this 3-tract tractography approach to facilitate VIM localization is illustrated with case examples of variable VIM location, targeting superior to the anterior commissure-posterior commissure plane, and treatment in the setting of pathologic derangement of thalamic anatomy. Finally, concepts demonstrated with these case examples and from the prior literature are synthesized to highlight several potential advantages of tractography for VIM region targeting.
MRgFUS of the nucleus ventralis intermedius in essential tremor modulates functional connectivity within the classical tremor network and beyond. [2023]Magnetic resonance-guided focused ultrasound (MRgFUS) of the thalamic ventral intermediate nucleus is an incisionless lesional treatment for essential tremor.
Assessing the impact of MR-guided focused ultrasound thalamotomy on brain activity and connectivity in patients with essential tremor. [2023]Although magnetic resonance-guided focused ultrasound (MRgFUS) at the ventral intermediate (VIM) thalamic nucleus is a novel and effective treatment for medication-refractory essential tremor (ET), it is unclear how the ablation lesion affects functional activity. The current study sought to evaluate the functional impact of MRgFUS thalamotomy in patients with ET, as well as to investigate the relationship between neuronal activity changes and tremor control.
Unilateral cerebellothalamic tract ablation in essential tremor by MRI-guided focused ultrasound. [2022]To report results of a prospective trial of unilateral transcranial MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract in essential tremor (ET).
MRI-guided focused-ultrasound thalamotomy in essential tremor: Immediate and delayed changes in cortico-muscular coherence and cortico-cortical out-strength. [2023]Drug-resistant essential tremor (ET) can be treated by Magnetic-Resonance-guided Focused-Ultrasound (MRgFUS) targeted to thalamic ventralis-intermediate nucleus (ViM). We are presenting the results obtained in ET patients by evaluating the cortico-muscular coherence (CMC) and the out-strength among cortical areas.