Essential Tremor
Conditions
Keywords
ExAblate Transcranial MRgFUS
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.
Interventions
DEVICETranscranial ExAblate
Sponsors
InSightec
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tremor Motor Score - Clinical Rating Scale for Tremor (CRST Part A (Upper Extremity) + Part B) Percent Change From Baseline | 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 | 5 Years post treatment. | The cumulative sum of adverse events was followed through Year 5 of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years 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 Follow Up were used to calculate percent change from baseline and averaged across subjects. High percent change from baseline is better (shows improvement). |
| Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post 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. |
| Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment | 1\. 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. |
| Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment | 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). |
Countries
Canada, Japan, South Korea, United States
Participant flow
Recruitment details
After completing the 3 Month visit subjects randomized to the Sham group were given the option to receive the Exablate thalamotomy as a rescue treatment and continue in the Crossover group. Nineteen subjects opted to continue in the Crossover group. Thus, 19 Sham Control and 19 Crossover are the same subjects. Two subjects randomized to the Exablate test group received suboptimal treatment, were retreated, and followed in the Crossover group through 12 Months resulting in N = 21.
Participants by arm
| Arm | Count |
|---|---|
| Transcranial ExAblate Transcranial ExAblate
Transcranial ExAblate | 56 |
| Sham Transcranial ExAblate Sham Treatment with Transcranial ExAblate
Sham Transcranial ExAblate | 20 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Long-term Annual Follow-up | Alternative Treatment | 4 | 0 | 1 |
| Long-term Annual Follow-up | Lack of Efficacy | 1 | 0 | 0 |
| Long-term Annual Follow-up | Lost to Follow-up | 2 | 0 | 0 |
| Long-term Annual Follow-up | Physician Decision | 1 | 0 | 0 |
| Long-term Annual Follow-up | Suboptimal Treatment | 1 | 0 | 0 |
| Long-term Annual Follow-up | Unrelated Health Reason | 2 | 0 | 1 |
| Long-term Annual Follow-up | Withdrawal by Subject | 11 | 0 | 5 |
| Main Continuation / Crossover Phase | Alternative treatment | 1 | 0 | 0 |
| Main Continuation / Crossover Phase | Health reasons unrelated to study | 1 | 0 | 0 |
| Main Continuation / Crossover Phase | Withdrawal by Subject | 1 | 0 | 0 |
| Main Study | Adverse Event | 1 | 0 | 0 |
| Main Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Transcranial ExAblate | Sham Transcranial ExAblate |
|---|---|---|---|
| Age, Continuous | 71.0 years STANDARD_DEVIATION 8.3 | 70.8 years STANDARD_DEVIATION 8.7 | 71.4 years STANDARD_DEVIATION 7.3 |
| CRST Part C Functional Disabilities Score | 16.4 Score on a Scale STANDARD_DEVIATION 4.53 | 16.5 Score on a Scale STANDARD_DEVIATION 4.64 | 16.1 Score on a Scale STANDARD_DEVIATION 4.32 |
| CRST Tremor Motor Score | 20.01 Score on a Scale STANDARD_DEVIATION 4.65 | 20.16 Score on a Scale STANDARD_DEVIATION 4.73 | 19.6 Score on a Scale STANDARD_DEVIATION 4.51 |
| Quality of Life for Essential Tremor (QUEST) Summary of Dimensions TOTAL Score | 42.6 Average of 5 Dimension Percent Scores STANDARD_DEVIATION 18.5 | 42.5 Average of 5 Dimension Percent Scores STANDARD_DEVIATION 18.3 | 42.8 Average of 5 Dimension Percent Scores STANDARD_DEVIATION 19.5 |
| Race/Ethnicity, Customized Asian | 18 Participants | 14 Participants | 4 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 57 Participants | 41 Participants | 16 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Canada | 16 participants | 12 participants | 4 participants |
| Region of Enrollment South Korea | 15 participants | 12 participants | 3 participants |
| Region of Enrollment United States | 45 participants | 32 participants | 13 participants |
| Sex: Female, Male Female | 24 Participants | 19 Participants | 5 Participants |
| Sex: Female, Male Male | 52 Participants | 37 Participants | 15 Participants |
| Skull Density Ratio | 0.6 Ratio STANDARD_DEVIATION 0.1 | 0.6 Ratio STANDARD_DEVIATION 0.1 | 0.5 Ratio STANDARD_DEVIATION 0.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 20 | 0 / 21 |
| other Total, other adverse events | 49 / 56 | 6 / 20 | 19 / 21 |
| serious Total, serious adverse events | 6 / 56 | 0 / 20 | 0 / 21 |
Outcome results
Primary
Number of Device and Procedure Related Adverse Events
The cumulative sum of adverse events was followed through Year 5 of the study.
Time frame: 5 Years post treatment.
Population: Adverse Events and Serious Adverse Events are reported in the Adverse Events Section. Nineteen of the 21 subjects were Sham group subjects opting for treatment in the Crossover group. Two out of the 21 received subtherapeutic treatment in the Transcranial Exablate group and were retreated and followed in the Crossover group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Transcranial ExAblate | Number of Device and Procedure Related Adverse Events | 184 Number of adverse events |
| Sham Transcranial ExAblate | Number of Device and Procedure Related Adverse Events | 26 Number of adverse events |
| Crossover Transcranial Exablate | Number of Device and Procedure Related Adverse Events | 75 Number of adverse events |
Primary
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).
Time frame: Baseline, 3 Months post-treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST Part A (Upper Extremity) + Part B) Percent Change From Baseline | 46.9 Percent Change from Baseline |
| Sham Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST Part A (Upper Extremity) + Part B) Percent Change From Baseline | -0.1 Percent Change from Baseline |
Comparison: Note that the Crossover group was a rescue treatment group and not integral to the experimental design statistical analysis.p-value: <0.001t-test, 1 sided
Secondary
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.
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Population: Subjects randomized to the Sham control group exited the study after completing the 3 month visit. They were given the opportunity to receive the Exablate treatment and complete the follow-up visit schedule. Nineteen Sham subjects opted to continue in the Crossover. Two subjects randomized to the Exablate group received suboptimal treatment, were retreated, and continued in the Crossover.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Transcranial ExAblate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 3 Month | 64.3 Percent Change from Baseline |
| Transcranial ExAblate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 6 Month | 62.5 Percent Change from Baseline |
| Transcranial ExAblate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 12 Month | 65.5 Percent Change from Baseline |
| Transcranial ExAblate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 2 Year | 73.8 Percent Change from Baseline |
| Transcranial ExAblate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 3 Year | 76.8 Percent Change from Baseline |
| Transcranial ExAblate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 4 Year | 72.0 Percent Change from Baseline |
| Transcranial ExAblate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 5 Year | 72.0 Percent Change from Baseline |
| Sham Transcranial ExAblate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 3 Month | -4.4 Percent Change from Baseline |
| Crossover Transcranial Exablate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 2 Year | 78.7 Percent Change from Baseline |
| Crossover Transcranial Exablate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 3 Month | 56.4 Percent Change from Baseline |
| Crossover Transcranial Exablate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 4 Year | 71.4 Percent Change from Baseline |
| Crossover Transcranial Exablate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 6 Month | 56.8 Percent Change from Baseline |
| Crossover Transcranial Exablate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 3 Year | 76.1 Percent Change from Baseline |
| Crossover Transcranial Exablate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 5 Year | 75.7 Percent Change from Baseline |
| Crossover Transcranial Exablate | Clinical Rating Scale (CRST) Part A - Posture Score, Percent Change From Baseline (Pre-treatment) | 12 Month | 46.4 Percent Change from Baseline |
Secondary
Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline
1\. 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.
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Population: Subjects randomized to the Sham control group exited the study after completing the 3 month visit. They were given the opportunity to receive the Exablate treatment and complete the follow-up visit schedule. Nineteen Sham subjects opted to continue in the Crossover. Two subjects randomized to the Exablate group received suboptimal treatment, were retreated and continued in the Crossover.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Transcranial ExAblate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 3 Months | 63.8 Percent Change from Baseline |
| Transcranial ExAblate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 6 Months | 61.8 Percent Change from Baseline |
| Transcranial ExAblate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 12 Months | 64.0 Percent Change from Baseline |
| Transcranial ExAblate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 2 Years | 62.1 Percent Change from Baseline |
| Transcranial ExAblate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 3 Years | 58.7 Percent Change from Baseline |
| Transcranial ExAblate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 4 Years | 47.8 Percent Change from Baseline |
| Transcranial ExAblate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 5 Years | 43.4 Percent Change from Baseline |
| Sham Transcranial ExAblate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 3 Months | 1.8 Percent Change from Baseline |
| Crossover Transcranial Exablate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 2 Years | 61.9 Percent Change from Baseline |
| Crossover Transcranial Exablate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 3 Months | 74.6 Percent Change from Baseline |
| Crossover Transcranial Exablate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 4 Years | 49.5 Percent Change from Baseline |
| Crossover Transcranial Exablate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 6 Months | 72.1 Percent Change from Baseline |
| Crossover Transcranial Exablate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 3 Years | 51.0 Percent Change from Baseline |
| Crossover Transcranial Exablate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 5 Years | 51.4 Percent Change from Baseline |
| Crossover Transcranial Exablate | Functional Disabilities - Clinical Rating Scale (CRST) for Tremor Part C Score Percent Change From Baseline | 12 Months | 68.9 Percent Change from Baseline |
Secondary
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).
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Population: Subjects randomized to the Sham control group exited the study after completing the 3 month visit. They were given the opportunity to receive the Exablate treatment and complete the follow-up visit schedule. Nineteen Sham subjects opted to continue in the Crossover. Two subjects randomized to the Exablate group received suboptimal treatment, were retreated, and continued in the Crossover.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Transcranial ExAblate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 3 Months | 43.2 Percent Change from Baseline |
| Transcranial ExAblate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 6 Months | 41.1 Percent Change from Baseline |
| Transcranial ExAblate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 12 Months | 47.1 Percent Change from Baseline |
| Transcranial ExAblate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 2 Years | 48.5 Percent Change from Baseline |
| Transcranial ExAblate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 3 Years | 41.0 Percent Change from Baseline |
| Transcranial ExAblate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 4 Years | 36.9 Percent Change from Baseline |
| Transcranial ExAblate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 5 Years | 31.2 Percent Change from Baseline |
| Sham Transcranial ExAblate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 3 Months | 5.0 Percent Change from Baseline |
| Crossover Transcranial Exablate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 2 Years | 49.2 Percent Change from Baseline |
| Crossover Transcranial Exablate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 3 Months | 59.2 Percent Change from Baseline |
| Crossover Transcranial Exablate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 4 Years | 21.7 Percent Change from Baseline |
| Crossover Transcranial Exablate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 6 Months | 58.4 Percent Change from Baseline |
| Crossover Transcranial Exablate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 3 Years | 24.3 Percent Change from Baseline |
| Crossover Transcranial Exablate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 5 Years | 16.6 Percent Change from Baseline |
| Crossover Transcranial Exablate | Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Total Percent Change From Baseline | 12 Months | 61.5 Percent Change from Baseline |
Secondary
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).
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Population: Subjects randomized to the Sham control group exited the study after completing the 3 month visit. They were given the opportunity to receive the Exablate treatment and complete the follow-up visit schedule. Nineteen Sham subjects opted to continue in the Crossover. Two subjects randomized to the Exablate group received suboptimal treatment, were retreated, and continued in the Crossover.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 3 Months | 46.9 Percent Change from Baseline |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 6 Months | 43.1 Percent Change from Baseline |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 12 Months | 39.6 Percent Change from Baseline |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 2 Years | 55.9 Percent Change from Baseline |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 3 Years | 52.6 Percent Change from Baseline |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 4 Years | 46.8 Percent Change from Baseline |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 5 Years | 37.5 Percent Change from Baseline |
| Sham Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 3 Months | -0.1 Percent Change from Baseline |
| Crossover Transcranial Exablate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 2 Years | 56.2 Percent Change from Baseline |
| Crossover Transcranial Exablate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 3 Months | 53.1 Percent Change from Baseline |
| Crossover Transcranial Exablate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 4 Years | 55.5 Percent Change from Baseline |
| Crossover Transcranial Exablate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 6 Months | 50.7 Percent Change from Baseline |
| Crossover Transcranial Exablate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 3 Years | 53.5 Percent Change from Baseline |
| Crossover Transcranial Exablate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 5 Years | 50.2 Percent Change from Baseline |
| Crossover Transcranial Exablate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Percent Change From Baseline | 12 Months | 47.0 Percent Change from Baseline |