Essential Tremor
Conditions
Brief summary
The objective of this prospective, multi site, single-arm study is to capture the efficacy of treatment using the ExAblate Transcranial System and to further demonstrate safety in medication-refractory tremor in patients 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 undergo an ExAblate treatment. All subjects will be followed at 1 day, 1 week, 1, 3, 6 and 12 months and for up to 5 years as directed by their doctor.
Interventions
DEVICETranscranial ExAblate
Transcranial ExAblate
Sponsors
InSightec
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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 |
|---|---|---|
| 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 Scores Summed | Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment | Sum of baseline and 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 calculated at baseline and follow-up visits averaged across subjects. Low scores are better (show improvement). |
| Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline | 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 minimum-maximum average score range is 0-4 and higher scores indicate worse outcomes. |
| Clinical Rating Scale for Tremor Part C - Activities of Daily Living. | Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment | Subject daily functionalities as measured by Clinical Rating Scale for Tremor Part C, CRST Part-C (subscales). CRST Part-C is an 8-item score with a minimum-maximum range of 0-32. Higher scores mean worse outcomes. |
| Quality of Life in Essential Tremor Total (QUEST) | Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment | The 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. Low Total scores are better. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transcranial ExAblate Transcranial ExAblate
Transcranial ExAblate: Transcranial ExAblate | 61 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Alternative Treatment | 4 |
| Overall Study | Inadequate Treatment | 2 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Withdrawal by Subject | 23 |
Baseline characteristics
| Characteristic | Transcranial ExAblate |
|---|---|
| Age, Continuous | 69.5 years STANDARD_DEVIATION 14 |
| Clinical Rating Scale for Tremor - Tremor Motor Score | 19.0 Score on a Scale STANDARD_DEVIATION 4.9 |
| CRST Part C Functional Disabilities Score | 16.7 Score on a Scale STANDARD_DEVIATION 4.87 |
| Family History of Essential Tremor No | 15 Participants |
| Family History of Essential Tremor Unknown | 1 Participants |
| Family History of Essential Tremor Yes | 45 Participants |
| Quality of Life for Essential Tremor (QUEST) Summary of Dimensions TOTAL Score | 42.9 Score on a scale STANDARD_DEVIATION 17.4 |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 57 Participants |
| Region of Enrollment United States | 61 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 41 Participants |
| Skull Density Ratio | 0.54 Ratio STANDARD_DEVIATION 0.1 |
| Years of Essential Tremor History | 19.5 years STANDARD_DEVIATION 14.2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 61 |
| other Total, other adverse events | 52 / 61 |
| serious Total, serious adverse events | 2 / 61 |
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 Presented in Adverse Events Section
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Transcranial ExAblate | Number of Device and Procedure Related Adverse Events. | 121 Number of adverse events |
Secondary
Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline
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 minimum-maximum average score range is 0-4 and higher scores indicate worse outcomes.
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Population: Sixty-one subjects were treated. Follow-up measures included all subjects completing the assessments. Subjects withdrawn from the study, missed visits, or missed assessments were included. Missing scores were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Transcranial ExAblate | Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline | Year 2 Follow Up | 0.5 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline | Baseline | 2.8 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline | Month 3 Follow Up | 0.7 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline | Month 6 Follow Up | 0.8 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline | Month 12 Follow Up | 0.7 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline | Year 3 Follow Up | 0.6 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline | Year 4 Follow Up | 0.7 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline | Year 5 Follow Up | 0.9 score on a scale |
Secondary
Clinical Rating Scale for Tremor Part C - Activities of Daily Living.
Subject daily functionalities as measured by Clinical Rating Scale for Tremor Part C, CRST Part-C (subscales). CRST Part-C is an 8-item score with a minimum-maximum range of 0-32. Higher scores mean worse outcomes.
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Population: The population includes all Exablate-treated subjects. Sample size at each visit includes all subjects excluding those that withdrew consent or missed the visit assessment. Missing scores were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Transcranial ExAblate | Clinical Rating Scale for Tremor Part C - Activities of Daily Living. | Baseline | 16.7 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor Part C - Activities of Daily Living. | Month 3 | 3.5 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor Part C - Activities of Daily Living. | Month 6 | 3.8 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor Part C - Activities of Daily Living. | Month 12 | 5.8 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor Part C - Activities of Daily Living. | 2 Year Follow Up | 6.1 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor Part C - Activities of Daily Living. | 3 Year Follow Up | 8.3 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor Part C - Activities of Daily Living. | 4 Year Follow Up | 8.4 score on a scale |
| Transcranial ExAblate | Clinical Rating Scale for Tremor Part C - Activities of Daily Living. | 5 Year Follow Up | 10.4 score on a scale |
Secondary
Quality of Life in Essential Tremor Total (QUEST)
The 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. Low Total scores are better.
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Population: The population includes all Exablate treated subjects except for those withdrawing consent or missing the assessment. Missing scores were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Transcranial ExAblate | Quality of Life in Essential Tremor Total (QUEST) | Baseline | 42.9 score on a scale |
| Transcranial ExAblate | Quality of Life in Essential Tremor Total (QUEST) | Month 3 | 17.8 score on a scale |
| Transcranial ExAblate | Quality of Life in Essential Tremor Total (QUEST) | Month 6 | 18.6 score on a scale |
| Transcranial ExAblate | Quality of Life in Essential Tremor Total (QUEST) | Month 12 | 19.60 score on a scale |
| Transcranial ExAblate | Quality of Life in Essential Tremor Total (QUEST) | Year 2 Follow Up | 21.0 score on a scale |
| Transcranial ExAblate | Quality of Life in Essential Tremor Total (QUEST) | Year 3 Follow Up | 24.0 score on a scale |
| Transcranial ExAblate | Quality of Life in Essential Tremor Total (QUEST) | Year 4 Follow Up | 22.5 score on a scale |
| Transcranial ExAblate | Quality of Life in Essential Tremor Total (QUEST) | Year 5 Follow Up | 25.1 score on a scale |
Secondary
Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Scores Summed
Sum of baseline and 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 calculated at baseline and follow-up visits averaged across subjects. Low scores are better (show improvement).
Time frame: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatment
Population: Sixty-one subjects were treated. Follow-up measures included all subjects completing the assessments. Subjects withdrawn from the study, missed visits, or missed assessments were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Scores Summed | Baseline | 19.0 score on a scale |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Scores Summed | Month 3 Follow Up | 6.3 score on a scale |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Scores Summed | Month 6 Follow Up | 7.0 score on a scale |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Scores Summed | Month 12 Follow Up | 7.4 score on a scale |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Scores Summed | 2 Year Follow Up | 7.3 score on a scale |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Scores Summed | 3 Year Follow Up | 7.3 score on a scale |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Scores Summed | 4 Year Follow Up | 7.9 score on a scale |
| Transcranial ExAblate | Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Scores Summed | 5 Year Follow Up | 9.2 score on a scale |