Essential TremorNCT01827904
ExAblate Transcranial MR Guided Focused Ultrasound for the Treatment of Essential Tremors
A study testing Transcranial ExAblate in people with Essential Tremor, run by InSightec at 8 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- Essential Tremor
- What is being tested?
- Transcranial ExAblate
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 8 sitesin 4 countries
- Study dates
- May 2013to 24 Feb 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States5 sites
University of Maryland Medical System
Baltimore, Maryland, 21201
Brigham and Women's Hospital
Boston, Massachusetts, 02115
University of Virginia
Charlottesville, Virginia, 22908
Swedish Medical Center
Seattle, Washington, 98122
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects
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).
Read the 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.
- Conditions
- Essential Tremor
- Being tested
- Transcranial ExAblate, Sham Transcranial ExAblate
- Keywords
- ExAblate Transcranial MRgFUS
- Medical subject headings
- Essential Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial ExAblateDevice
Also called ExAblate, TcMRgFUS, Thalamotomy
Sham Transcranial ExAblateDevice
| Study group | Role | What they receive |
|---|---|---|
| Transcranial ExAblate | Experimental | Transcranial ExAblate Receives: Device: Transcranial ExAblate |
| Sham Transcranial ExAblate | Sham comparator | Sham Treatment with Transcranial ExAblate Receives: Device: Sham Transcranial ExAblate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tremor Motor Score - Clinical Rating Scale for Tremor (CRST Part A (Upper Extremity) + Part B) Percent Change From Baseline
The percent 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 that was 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 were used to calculate percent change from baseline and averaged across subjects. High percent change from baseline is better (shows improvement).
Measured: Baseline, 3 Months post-treatment
Number of Device and Procedure Related Adverse Events
The cumulative sum of adverse events was followed through Year 5 of the study.
Measured: 5 Years post treatment.
Secondary outcomes (4)
Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline
The percent 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 that was 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 Follow Up were used to calculate percent change from baseline and averaged across subjects. High percent change from baseline is better (shows improvement).
Measured: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment)
The Posture Score is a sub-Score of the Clinical Rating Scale for Tremor CRST Part A - Posture (Treated Side Upper Extremity Posture Score). The scores range 0-12 and higher scores indicate worse outcomes. For percent improvement compared to Baseline (pre-treatment visit) higher percents mean better outcomes.
Measured: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline
- Subject daily functionalities: as measured by CRST Part-C (subscales) as percent change from Baseline. CRST Part-C is an 8-item score range 0-32. Higher percent change from Baseline means better outcomes.
Measured: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline
The percent change from baseline to follow-up QUEST Summary Total was used to assess quality of life changes over time in tremor patients. The QUEST consists of five dimensions for each subject converted to a percent of the total (0-100%). The summary total is the average of the five dimensions. High percent change from baseline is better (shows improvement).
Measured: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2013 (estimated)
- Study startMay 2013
- Primary completion24 Feb 2021
- Study completion24 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Essential TremorStudies of the same condition, open and under way.
- More trials run by InSightecThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- InSightec
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01827904
- Sponsor's protocol ID
- ET002
- Status last verified
- Mar 2024
- First submitted
- 27 Mar 2013
- Last updated
- 27 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 35995551Cosgrove 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.
PubMed 35932269Halpern 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.
PubMed 31748250Elias 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.
PubMed 27557301
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects
- ClinicalTrials.gov ID
- NCT01827904
- Acronym / sponsor ID
- ET002
- Conditions
- Essential Tremor
- Keywords
- ExAblate Transcranial MRgFUS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- InSightecIndustry (pharma, biotech, devices)
- Study start
- May 2013 (actual)
- Primary completion
- 24 Feb 2021 (actual)
- Study completion
- 24 Feb 2021 (actual)
- First posted
- 10 Apr 2013 (estimated)
- Results
- Posted 13 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transcranial ExAblate | Experimental | Device: Transcranial ExAblateTranscranial ExAblate |
| Sham Transcranial ExAblate | Sham comparator | Device: Sham Transcranial ExAblateSham Treatment with Transcranial ExAblate |
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial ExAblateAlso: ExAblate, TcMRgFUS, Thalamotomy | Device | Transcranial ExAblate |
| Sham Transcranial ExAblate | Device | Sham Transcranial ExAblate |
Primary outcome
Tremor Motor Score - Clinical Rating Scale for Tremor (CRST Part A (Upper Extremity) + Part B) Percent Change From Baseline
Time frame: Baseline, 3 Months post-treatment
The percent 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 that was 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 were used to calculate percent change from baseline and averaged across subjects. High percent change from baseline is better (shows improvement).
Number of Device and Procedure Related Adverse Events
Time frame: 5 Years post treatment.
The cumulative sum of adverse events was followed through Year 5 of the study.
4 secondary outcomes
Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment)
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35995551Yamamoto 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.
- Derived from this study: PubMed 35932269Cosgrove 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.
- Derived from this study: PubMed 31748250Halpern 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.
- Derived from this study: PubMed 27557301Elias 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.
Related trials for Essential Tremor
RecruitingObservational study
The Encora X1™ in a Real World Observational Study
Essential Tremor
Recruiting
Deep Brain Stimulation Surgery for Movement Disorders
Parkinson's Disease, Essential Tremor
RecruitingObservational study
Analysis of Cutaneous Phosphorylated Alpha-Synuclein to Identify Patients at Risk of Progressing From Essential Tremor to Parkinson's Disease
Essential Tremor, Movement Disorders, Essential Tremor
Recruiting
Effects of Microelectrode-based Brain Stimulation in Humans
Essential Tremor, Parkinsons Disease (PD)
Active, not recruitingObservational study
Identifying Markers of Disease Subtypes and Disease Progression in the Syndrome of Essential Tremor
Essential Tremor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial ExAblate in people with Essential Tremor, run by InSightec at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Canada, Japan, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tremor Motor Score - Clinical Rating Scale for Tremor (CRST Part A (Upper Extremity) + Part B) Percent Change From Baseline (time frame: Baseline, 3 Months post-treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01827904, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2024.