Clinical trial NCT06331052: 3-D Tractography FUS Ablation for Essential Tremor
Official title: 3-D Tractography Focused Ultrasound Ablation for Essential Tremor
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Essential Tremor
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Texas Tech University Health Sciences Center, El Paso
name: University of Pittsburgh
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2024-03-26
Enrollment: 24
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Number of Participants without Side Effects
timeFrame: during the surgical procedure
measure: Absolute Change in Tremor
timeFrame: Baseline, Month 3
measure: Relative Change in Tremor
timeFrame: Baseline, Month 3
Secondary outcomes:
measure: Number of Participants with Procedure-Related Side Effects
timeFrame: 3 months after the surgical procedure
measure: Relative Change in Tremor-Related Quality of Life
timeFrame: 3 months after the surgical procedure
measure: Number of Participants Who Are Satisfied with Treatment
timeFrame: 3 months after the surgical procedure
Other outcomes:
measure: Change in Tremor Based on Video Assessment
timeFrame: Baseline, during the surgical procedure
measure: Change in Gait Based on Video Assessment
timeFrame: Baseline, during the surgical procedure
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina at Chapel Hll
name: Vibhor Krishna, MD
role: PRINCIPAL_INVESTIGATOR
References: