3-D Tractography FUS Ablation for Essential Tremor

NCT ID: NCT06331052

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-28
• Study Completion Date: 2028-02-28

Brief Summary

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.

Detailed Description

Essential tremor (ET) is a common neurological disorder and a leading cause of functional and psychological disabilities that can be difficult to suppress with oral medications, many of which have considerable side effects limiting adequate dosing. As a result, up to 20% of ET patients cannot achieve satisfactory control of their symptoms and must consider interventional options. Focused ultrasound ablation (FUSA) of the ventral intermediate nucleus (Vim) is an FDA-approved and Medicare-reimbursed procedure for ET resistant to medications that can selectively ablate the brain area associated with tremor without the need for surgical incisions or anesthesia. The success of Vim-FUSA depends on the ability to accurately ablate 70% of the Vim volume without lesioning neighboring structures, a goal that is complicated by technical challenges in three critical phases of the procedure: planning (identifying the Vim location and extension); delivery (ablating the Vim volume with adequate accuracy); and monitoring (confirming Vim ablation with reliable intraoperative imaging). The investigators propose to advance Vim-FUSA 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. Aim 1. Estimate and characterize the improvement in Vim ablation achieved with 3-D tractography Vim-FUSA vs. standard Vim-FUSA in an experimental controlled animal study. Through an experimental animal study, the investigators will characterize the Vim ablation delivered with 3-D tractography Vim-FUSA in one hemisphere (experimental group) vs. standard Vim-FUSA in the opposite hemisphere (control group). Aim 2. Test safety, feasibility, and preliminary efficacy, and estimate effect size of 3-D tractography Vim-FUSA in a phase-II, two-groups, pre-post interventional human study. In a human study, the investigators will test the safety and feasibility of ablating 70% of the Vim volume while checking for side effects with intraoperative clinical testing. Tremor assessments will be videotaped at baseline and 12 weeks and compared, in a blinded fashion, with age-sex matched controls randomly selected from the video repository of the two FDA-regulated studies of standard Vim-FUSA at baseline and 12 weeks. Aim 3 (Exploratory). Assess the accuracy of i-MR in differentiating tissue ablation from immediate perilesional edema and its utility in predicting Vim-FUSA clinical outcomes. In the experimental animal study, the investigators will estimate and compare the accuracy of conventional and non-conventional i-MR in differentiating tissue necrosis from perilesional edema. In the interventional human study, the investigators will evaluate the utility of i-MR in predicting Vim-FUSA clinical outcomes

Conditions

Essential Tremor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

3-D Tractography Vim FUSA

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

Group Type: EXPERIMENTAL

MR-guided Focused Ultrasound Ablation

Intervention Type: DEVICE

3-D tractography Vim-FUSA -D tractography Vim-FUSA will be carried out as follows: (a) head shaving and placement of the stereotactic frame (Integra radionics frame, Integra Lifesciences, NJ, USA) secured to the skull with transcutaneous screws; (b) positioning on the procedure table and placement of the ultrasound transducer; (c) acquisition of conventional magnetic resonance (MR) imaging and co-registration with the CT head and 3-D tractography imaging acquired pre-surgically; (d) exploration of the target area with subtherapeutic sonications; (e) intraoperative monitoring with clinical testing of tremor and side effects with a standardized protocol. (f) Therapeutic sonications in the target area to deliver definitive ablation followed by clinical testing of tremor and side effects with a standardized protocol as described in section (e).

Interventions

MR-guided Focused Ultrasound Ablation

3-D tractography Vim-FUSA -D tractography Vim-FUSA will be carried out as follows: (a) head shaving and placement of the stereotactic frame (Integra radionics frame, Integra Lifesciences, NJ, USA) secured to the skull with transcutaneous screws; (b) positioning on the procedure table and placement of the ultrasound transducer; (c) acquisition of conventional magnetic resonance (MR) imaging and co-registration with the CT head and 3-D tractography imaging acquired pre-surgically; (d) exploration of the target area with subtherapeutic sonications; (e) intraoperative monitoring with clinical testing of tremor and side effects with a standardized protocol. (f) Therapeutic sonications in the target area to deliver definitive ablation followed by clinical testing of tremor and side effects with a standardized protocol as described in section (e).

Intervention Type: DEVICE

Other Intervention Names

3-D Tractography

Eligibility Criteria

Inclusion Criteria

• Diagnosis of moderate to severe ET agreed upon by at least two movement disorder trained physicians
• Symptoms refractory to at least two medications
• Stable medication regimen for at least 4 weeks prior to screening
• Willing and able to participate in all follow-up visits
• Willing and able to undergo MR imaging.

Exclusion Criteria

• Uncontrolled hypertension
• Medically unstable coronary artery disease
• Coagulopathy, anticoagulant therapy, or inability to temporarily stop any antithrombotic medication
• Tremor disorders other than ET
• Unwilling or unable to undergo tremor surgery while awake
• Significant and non-correctible motion artifact in imaging
• Pregnant at the time of enrollment or preoperative evaluation
• Dementia
• History of psychosis
• History of drug or alcohol abuse
• Prior brain surgery such as Vim-FUSA, deep brain stimulation, and gamma knife thalamotomy
• Botulinum toxin injection in the tremor-impacted areas three months prior to the baseline assessment and until 3-months after Vim-FUSA
• Skull density ratio lower than 0.4
• Does not qualify for FDA-approved clinical use based on current FDA labeling
• Any significant issue raised by the neurologist or neurosurgeon that may compromise participant safety or potentially interfere with study interpretation.

• Minimum Eligible Age: 22 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Texas Tech University Health Sciences Center, El Paso

OTHER

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vibhor Krishna, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina at Chapel Hll

Locations

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Vibhor Krishna, MD

Role: CONTACT

vibhor_krishna@med.unc.edu

+1(919)-445-2410

Victoria Scott

Role: CONTACT

Victoria_Scott@med.unc.edu

919-966-0864

Facility Contacts

Victoria Scott

Role: primary

Victoria_Scott@med.unc.edu

919-966-0864

Vibhor Krishna, MD, SM

Role: backup

vibhor_krishna@med.unc.edu

919-445-2410

Other Identifiers

23-2431

Identifier Type: -

Identifier Source: org_study_id

1R01NS125386-01

Identifier Type: NIH

Identifier Source: secondary_id

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