Clinical trial NCT01827904: ExAblate Transcranial MR Guided Focused Ultrasound for the Treatment of Essential Tremors
Official title: A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Essential Tremor
Keywords: ExAblate Transcranial MRgFUS
Lead sponsor: InSightec
Sponsor class: INDUSTRY
First posted: 2013-04-10
Enrollment: 76
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

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.

Eligibility 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

Primary outcomes:
measure: Tremor Motor Score - Clinical Rating Scale for Tremor (CRST Part A (Upper Extremity) + Part B) Percent Change From Baseline
timeFrame: Baseline, 3 Months post-treatment
measure: Number of Device and Procedure Related Adverse Events
timeFrame: 5 Years post treatment.
Secondary outcomes:
measure: Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline
timeFrame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
measure: Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment)
timeFrame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
measure: Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline
timeFrame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
measure: Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline
timeFrame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Baltimore
country: United States
facility: University of Maryland Medical System
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University (TWMU)
city: Seoul
country: Korea, Republic of
facility: Yonsei University Medical Center
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.