3-D Tractography FUS Ablation for Essential Tremor
- Conditions
- Essential Tremor
- Interventions
- Device: MR-guided Focused Ultrasound Ablation
- Registration Number
- NCT06331052
- Lead Sponsor
- University of North Carolina, Chapel Hill
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 3-D Tractography Vim FUSA MR-guided Focused Ultrasound Ablation Twenty-four consecutive essential tremor (ET) participants undergoing Vim FUSA using 3-D tractography will be assessed at baseline and Month 3.
- Primary Outcome Measures
Name Time Method Number of Participants without Side Effects during the surgical procedure Feasibility is defined as the ability to complete the procedure without side effects.
Absolute Change in Tremor Baseline, Month 3 The absolute change from baseline to Month 3 follow-up in upper extremity Tremor-Motor scores for the treated side is a sub-scale of Clinical Rating Scale for Tremor (CRST) Part A and Part B sum used to measure treated-side upper extremity tremor changes over time. Tremor-motor scores range from 0-32 points. Individual subject's scores at Baseline and 3 Months used to calculate absolute change from baseline and averaged across subjects. High absolute change from baseline is better (shows improvement).
Relative Change in Tremor Baseline, Month 3 The relative change from baseline to Month 3 follow-up in upper extremity Tremor-Motor scores for the treated side is a sub-scale of Clinical Rating Scale for Tremor (CRST) Part A and Part B sum used to measure treated-side upper extremity tremor changes over time. Tremor-motor scores range from 0-32 points. Individual subject's scores at Baseline and 3 Months used to calculate relative change from baseline and averaged across subjects. High relative change from baseline is better (shows improvement).
- Secondary Outcome Measures
Name Time Method Number of Participants with Procedure-Related Side Effects 3 months after the surgical procedure Prevalence and severity of procedure-related side effects measured by the following: ataxia (SARA), speech disturbance (VHI), sensory loss (SWME), muscle weakness (MRC)
Relative Change in Tremor-Related Quality of Life 3 months after the surgical procedure The Quality of Life Essential Tremor Questionnaire (QUEST) will be used to assess tremor-related quality of life. QUEST has scores ranging from 0 to 100 with higher scores indicating worse disability.
Number of Participants Who Are Satisfied with Treatment 3 months after the surgical procedure Measured using a single question asking about patient satisfaction ranging from 1 to 5 with higher scores indicating higher satisfaction.
Trial Locations
- Locations (1)
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States