3-D Tractography FUS Ablation for Essential Tremor

Essential Tremor Clinical Trial

Official title:

3-D Tractography Focused Ultrasound Ablation for Essential Tremor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06331052
• Other study ID #: 23-2431
• Secondary ID: 1R01NS125386-01
• Status: Recruiting
• Phase: N/A
• Start date: February 28, 2024
• Est. completion date: February 28, 2028

Study information

• Verified date: March 2024
• Source: University of North Carolina, Chapel Hill
• Contact: Mary Ann Barnett
• Phone: +1 (919)-966-8804
• Email: Mary-Ann_Barnett[@]med.unc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: February 28, 2028
• Est. primary completion date: February 28, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Essential Tremor
• Tremor

Intervention

Device:
• 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).

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Neurological Disorders and Stroke (NINDS), Texas Tech University Health Sciences Center, El Paso, University of Pittsburgh

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Tremor Based on Video Assessment	Upper extremity tremors will be measured by video recording using i-Phone set-up.	Baseline, during the surgical procedure
Other	Change in Gait Based on Video Assessment	Gait will be measured by video recording using i-Phone set-up.	Baseline, during the surgical procedure
Primary	Number of Participants without Side Effects	Feasibility is defined as the ability to complete the procedure without side effects.	during the surgical procedure
Primary	Absolute Change in Tremor	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).	Baseline, Month 3
Primary	Relative Change in Tremor	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).	Baseline, Month 3
Secondary	Number of Participants with Procedure-Related Side Effects	Prevalence and severity of procedure-related side effects measured by the following: ataxia (SARA), speech disturbance (VHI), sensory loss (SWME), muscle weakness (MRC)	3 months after the surgical procedure
Secondary	Relative Change in Tremor-Related Quality of Life	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.	3 months after the surgical procedure
Secondary	Number of Participants Who Are Satisfied with Treatment	Measured using a single question asking about patient satisfaction ranging from 1 to 5 with higher scores indicating higher satisfaction.	3 months after the surgical procedure