ExAblate Transcranial MR Guided Focused Ultrasound for the Treatment of Essential Tremors

• ClinicalTrials.gov Identifier: NCT01827904
• Recruitment Status: Active, not recruiting
• First Posted: April 10, 2013
• Last Update Posted: March 31, 2022
• Sponsor: InSightec
• Information provided by (Responsible Party): InSightec

Study Description

Brief Summary:

The objective of this prospective, randomized, double-blind (to subjects, local site's blinded assessor and Tremor Core Lab assessors), crossover, multi-site, two-arm study (ExAblate treated arm Vs ExAblate Sham treated control arm) is to test the efficacy of treatment using the ExAblate Transcranial System and to further demonstrate safety in medication-refractory tremor in subjects with essential tremor (ET).

Condition or disease	Intervention/treatment	Phase
Essential Tremor	Device: Transcranial ExAblate; Device: Sham Transcranial ExAblate	Not Applicable

Detailed Description:

This study is evaluating a new technique for performing Thalamotomy for tremor control. While current techniques have possible invasive or radiation effects, the use of ExAblate if totally non-invasive and without any radiation. After informed consent and screening, eligible subjects will be randomized to either an ExAblate treatment or an ExAblate Sham or "fake" procedure. The chance of randomization to Sham is one out of four. Subjects who are randomized to Sham Control will undergo the same procedure and follow-up visits through their Month 3 visit. After the Month 3 assessments are complete, all subjects will be unblinded and those in the Sham treated group will have the option for an actual ExAblate treatment in an unblinded fashion, as long as they still qualify for ExAblate treatment. All subjects will be followed at 6 and 12 months and for up to 5 years as directed by their doctor.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects
• Study Start Date: May 2013
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Transcranial ExAblate; Transcranial ExAblate	Device: Transcranial ExAblate; Other Names: ExAblate; TcMRgFUS; Thalamotomy
Sham Comparator: Sham Transcranial ExAblate; Sham Treatment with Transcranial ExAblate	Device: Sham Transcranial ExAblate

Outcome Measures

Primary Outcome Measures :

1. Primary Efficacy Outcome [ Time Frame: Participants will be followed from the date of treatment until study completion, approximately up to 12 months ]
   The treated upper limb CRST subscore (CRST A + B) applicable to upper limb in the ExAblate Group will be statistically better than the Sham control Group at Month 3
2. Severity of Device and Procedure related complications [ Time Frame: At the time of ExAblate Transcranial thalamotomy procedure ]
   To evaluate the incidence and severity of adverse events (AEs) associated with the ExAblate Transcranial thalamotomy of medication-refractory Essential Tremor related to the ExAblate treatment

Secondary Outcome Measures :

1. Clinical Rating Scale for Tremor Part C Score [ Time Frame: Participants will be followed from the date of treatment until study completion, approximately up to 12 months ]
   1. Subject daily functionalities: as measured by CRST Part-C (subscales) Month 12 as compared to Baseline, and between treatment groups through Month 3
   2. Durability (as measured by QUEST upper arm extremity questions) of the procedure as reflected by the efficacy data through change from baseline measures through Month 12 follow up
   3. Quality life claims: Questionnaire for Essential Tremor (QUEST) outcome (upper extremity questions) at Months 3 change from Baseline.as compared between treatment groups

Eligibility Criteria

• Ages Eligible for Study: 22 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men and women, age 22 years and older
• Subjects who are able and willing to give informed consent and able to attend all study visits
• Subjects with a diagnosis of Essential Tremor as confirmed from clinical history and examination by a neurologist or neurosurgeon specialized in movement disorder
• Subject exhibits a significant disability from their ET despite medical treatment
• Subjects should be on a stable dose of all ET medications for 30 days prior to study entry
• Subject is able to communicate sensations during the ExAblate Transcranial procedure

Exclusion Criteria:

• Subjects with unstable cardiac status
• Severe hypertension
• Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
• Known intolerance or allergies to the MRI contrast agent including advanced kidney disease or severely impaired renal function
• Significant claustrophobia that cannot be managed with mild medication
• Current medical condition resulting in abnormal bleeding and/or coagulopathy
• Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage
• History of intracranial hemorrhage
• History of multiple strokes, or a stroke within past 6 months
• Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment
• Are participating or have participated in another clinical trial in the last 30 days
• Subjects unable to communicate with the investigator and staff
• Subjects with a history of seizures within the past year
• Subjects with brain tumors

Contacts and Locations

Locations

United States, California

Stanford University Medical Center

Stanford, California, United States, 94305

United States, Maryland

University of Maryland Medical System

Baltimore, Maryland, United States, 21201

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Virginia

University of Virginia

Charlottesville, Virginia, United States, 22908

United States, Washington

Swedish Medical Center

Seattle, Washington, United States, 98122

Canada, Ontario

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, M4N 3M5

Japan

Tokyo Women's Medical University (TWMU)

Tokyo, Japan, 162-8666

Korea, Republic of

Yonsei University Medical Center

Seoul, Korea, Republic of, 120-752

Sponsors and Collaborators

InSightec

More Information

Study Data/Documents: Clinical Study Report 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yamamoto K, Sarica C, Elias GJB, Boutet A, Germann J, Loh A, Joel SE, Bigioni L, Gwun D, Gramer R, Li SX, Zemmar A, Vetkas A, Algarni M, Devenyi G, Chakravarty M, Hynynen K, Scantlebury N, Schwartz ML, Lozano AM, Fasano A. Ipsilateral and axial tremor response to focused ultrasound thalamotomy for essential tremor: clinical outcomes and probabilistic mapping. J Neurol Neurosurg Psychiatry. 2022 Aug 22:jnnp-2021-328459. doi: 10.1136/jnnp-2021-328459. Online ahead of print.

Cosgrove GR, Lipsman N, Lozano AM, Chang JW, Halpern C, Ghanouni P, Eisenberg H, Fishman P, Taira T, Schwartz ML, McDannold N, Hayes M, Ro S, Shah B, Gwinn R, Santini VE, Hynynen K, Elias WJ. Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: 5-year follow-up results. J Neurosurg. 2022 Aug 5;138(4):1028-1033. doi: 10.3171/2022.6.JNS212483. Print 2023 Apr 1.

Halpern CH, Santini V, Lipsman N, Lozano AM, Schwartz ML, Shah BB, Elias WJ, Cosgrove GR, Hayes MT, McDannold N, Aldrich C, Eisenberg HM, Gandhi D, Taira T, Gwinn R, Ro S, Witt J, Jung NY, Chang JW, Rosenberg J, Ghanouni P. Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor. Neurology. 2019 Dec 10;93(24):e2284-e2293. doi: 10.1212/WNL.0000000000008561. Epub 2019 Nov 20.

Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W, Schwartz M, Hynynen K, Lozano AM, Shah BB, Huss D, Dallapiazza RF, Gwinn R, Witt J, Ro S, Eisenberg HM, Fishman PS, Gandhi D, Halpern CH, Chuang R, Butts Pauly K, Tierney TS, Hayes MT, Cosgrove GR, Yamaguchi T, Abe K, Taira T, Chang JW. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N Engl J Med. 2016 Aug 25;375(8):730-9. doi: 10.1056/NEJMoa1600159.

• Responsible Party: InSightec
• ClinicalTrials.gov Identifier: NCT01827904
• Other Study ID Numbers: ET002
• First Posted: April 10, 2013
• Last Update Posted: March 31, 2022
• Last Verified: August 2021

Keywords provided by InSightec:

ExAblate Transcranial MRgFUS

Additional relevant MeSH terms:

Tremor; Essential Tremor; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Movement Disorders; Central Nervous System Diseases