Trial Outcomes & Findings for Continued Access Protocol: ExAblate Transcranial MR Guided Focused Ultrasound for the Treatment of Essential Tremors (NCT NCT02289560)
NCT ID: NCT02289560
Last Updated: 2024-07-03
Results Overview
The cumulative sum of adverse events was followed through Year 5 of the study.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
61 participants
Primary outcome timeframe
5 Years post treatment
Results posted on
2024-07-03
Participant Flow
Participant milestones
| Measure |
Transcranial Exablate
Transcranial Exablate: This was a single-arm study with no proposed hypothesis. All subjects were treated with unilateral transcranial Exablate for essential tremor.
|
|---|---|
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Overall Study
STARTED
|
61
|
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Overall Study
COMPLETED
|
26
|
|
Overall Study
NOT COMPLETED
|
35
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Reasons for withdrawal
| Measure |
Transcranial Exablate
Transcranial Exablate: This was a single-arm study with no proposed hypothesis. All subjects were treated with unilateral transcranial Exablate for essential tremor.
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|---|---|
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Overall Study
Lost to Follow-up
|
6
|
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Overall Study
Alternative Treatment
|
4
|
|
Overall Study
Inadequate Treatment
|
2
|
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Overall Study
Withdrawal by Subject
|
23
|
Baseline Characteristics
Birth date was not reported for three subjects
Baseline characteristics by cohort
| Measure |
Transcranial ExAblate
n=61 Participants
Transcranial ExAblate
Transcranial ExAblate: Transcranial ExAblate
|
|---|---|
|
Age, Continuous
|
69.5 years
STANDARD_DEVIATION 14.0 • n=58 Participants • Birth date was not reported for three subjects
|
|
Sex: Female, Male
Female
|
20 Participants
n=61 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=61 Participants
|
|
Race/Ethnicity, Customized
White
|
57 Participants
n=61 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
0 Participants
n=61 Participants
|
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Race/Ethnicity, Customized
Black
|
0 Participants
n=61 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=61 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=61 Participants
|
|
Region of Enrollment
United States
|
61 participants
n=61 Participants
|
|
Family History of Essential Tremor
Yes
|
45 Participants
n=61 Participants
|
|
Family History of Essential Tremor
No
|
15 Participants
n=61 Participants
|
|
Family History of Essential Tremor
Unknown
|
1 Participants
n=61 Participants
|
|
Years of Essential Tremor History
|
19.5 years
STANDARD_DEVIATION 14.2 • n=60 Participants • Family history of essential tremor was not reported for one subject out of 61. Thus, n=60 subjects were available for summary statistical analysis.
|
|
Skull Density Ratio
|
0.54 Ratio
STANDARD_DEVIATION 0.10 • n=57 Participants • SDR was not reported for four subjects
|
|
Clinical Rating Scale for Tremor - Tremor Motor Score
|
19.0 Score on a Scale
STANDARD_DEVIATION 4.9 • n=61 Participants
|
|
Quality of Life for Essential Tremor (QUEST) Summary of Dimensions TOTAL Score
|
42.9 Score on a scale
STANDARD_DEVIATION 17.4 • n=61 Participants
|
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CRST Part C Functional Disabilities Score
|
16.7 Score on a Scale
STANDARD_DEVIATION 4.87 • n=61 Participants
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PRIMARY outcome
Timeframe: 5 Years post treatmentPopulation: Adverse Events and Serious Adverse Events are Presented in Adverse Events Section
The cumulative sum of adverse events was followed through Year 5 of the study.
Outcome measures
| Measure |
Transcranial ExAblate
n=61 Participants
Transcranial ExAblate
Transcranial ExAblate: Transcranial ExAblate
|
|---|---|
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Number of Device and Procedure Related Adverse Events.
|
121 Number of adverse events
|
SECONDARY outcome
Timeframe: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatmentPopulation: 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.
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).
Outcome measures
| Measure |
Transcranial ExAblate
n=61 Participants
Transcranial ExAblate
Transcranial ExAblate: 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
Interval 5.43 to 8.57
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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
Interval 5.81 to 8.9
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|
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
Interval 5.8 to 8.78
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|
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
Interval 5.66 to 8.91
|
|
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
Interval 5.92 to 9.95
|
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Tremor Motor Score - Clinical Rating Scale for Tremor (CRST) Part A (Upper Extremity) + Part B Scores Summed
Baseline
|
19.0 score on a scale
Interval 17.8 to 20.26
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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
Interval 4.88 to 7.7
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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
Interval 6.7 to 11.73
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SECONDARY outcome
Timeframe: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatmentPopulation: 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.
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.
Outcome measures
| Measure |
Transcranial ExAblate
n=61 Participants
Transcranial ExAblate
Transcranial ExAblate: Transcranial ExAblate
|
|---|---|
|
Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline
Baseline
|
2.8 score on a scale
Interval 2.54 to 3.01
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Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline
Month 3 Follow Up
|
0.7 score on a scale
Interval 0.44 to 0.88
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Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline
Month 6 Follow Up
|
0.8 score on a scale
Interval 0.55 to 1.06
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Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline
Month 12 Follow Up
|
0.7 score on a scale
Interval 0.46 to 0.9
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Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline
Year 2 Follow Up
|
0.5 score on a scale
Interval 0.29 to 0.69
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Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline
Year 3 Follow Up
|
0.6 score on a scale
Interval 0.39 to 0.78
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Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline
Year 4 Follow Up
|
0.7 score on a scale
Interval 0.38 to 0.93
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Clinical Rating Scale for Tremor (CRST Part A) Posture Score Change From Baseline
Year 5 Follow Up
|
0.9 score on a scale
Interval 0.51 to 1.32
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SECONDARY outcome
Timeframe: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatmentPopulation: 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.
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.
Outcome measures
| Measure |
Transcranial ExAblate
n=61 Participants
Transcranial ExAblate
Transcranial ExAblate: Transcranial ExAblate
|
|---|---|
|
Clinical Rating Scale for Tremor Part C - Activities of Daily Living.
Month 3
|
3.5 score on a scale
Interval 2.47 to 4.46
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Clinical Rating Scale for Tremor Part C - Activities of Daily Living.
Month 6
|
3.8 score on a scale
Interval 2.41 to 5.09
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Clinical Rating Scale for Tremor Part C - Activities of Daily Living.
Month 12
|
5.8 score on a scale
Interval 4.2 to 7.46
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Clinical Rating Scale for Tremor Part C - Activities of Daily Living.
2 Year Follow Up
|
6.1 score on a scale
Interval 4.39 to 7.74
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Clinical Rating Scale for Tremor Part C - Activities of Daily Living.
5 Year Follow Up
|
10.4 score on a scale
Interval 7.26 to 13.52
|
|
Clinical Rating Scale for Tremor Part C - Activities of Daily Living.
Baseline
|
16.7 score on a scale
Interval 15.47 to 17.91
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Clinical Rating Scale for Tremor Part C - Activities of Daily Living.
3 Year Follow Up
|
8.3 score on a scale
Interval 5.95 to 10.62
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Clinical Rating Scale for Tremor Part C - Activities of Daily Living.
4 Year Follow Up
|
8.4 score on a scale
Interval 6.12 to 10.7
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SECONDARY outcome
Timeframe: Baseline, 3 Months, 6 Months, 12 Months, 2, 3, 4, 5 Years post treatmentPopulation: The population includes all Exablate treated subjects except for those withdrawing consent or missing the assessment. Missing scores were not imputed.
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.
Outcome measures
| Measure |
Transcranial ExAblate
n=61 Participants
Transcranial ExAblate
Transcranial ExAblate: Transcranial ExAblate
|
|---|---|
|
Quality of Life in Essential Tremor Total (QUEST)
Baseline
|
42.9 score on a scale
Interval 38.51 to 47.25
|
|
Quality of Life in Essential Tremor Total (QUEST)
Month 3
|
17.8 score on a scale
Interval 12.81 to 22.71
|
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Quality of Life in Essential Tremor Total (QUEST)
Month 6
|
18.6 score on a scale
Interval 13.64 to 23.52
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Quality of Life in Essential Tremor Total (QUEST)
Month 12
|
19.60 score on a scale
Interval 14.22 to 24.88
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|
Quality of Life in Essential Tremor Total (QUEST)
Year 2 Follow Up
|
21.0 score on a scale
Interval 15.24 to 26.84
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Quality of Life in Essential Tremor Total (QUEST)
Year 3 Follow Up
|
24.0 score on a scale
Interval 17.75 to 30.17
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Quality of Life in Essential Tremor Total (QUEST)
Year 4 Follow Up
|
22.5 score on a scale
Interval 15.59 to 29.44
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Quality of Life in Essential Tremor Total (QUEST)
Year 5 Follow Up
|
25.1 score on a scale
Interval 15.98 to 34.3
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Adverse Events
Transcranial Exablate
Serious events: 2 serious events
Other events: 52 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Transcranial Exablate
n=61 participants at risk
Transcranial Exablate
Transcranial Exablate: Transcranial Exablate
|
|---|---|
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Nervous system disorders
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Cardiac disorders
Myocardial Infarction.
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
Other adverse events
| Measure |
Transcranial Exablate
n=61 participants at risk
Transcranial Exablate
Transcranial Exablate: Transcranial Exablate
|
|---|---|
|
Gastrointestinal disorders
Nausea/Vomiting
|
3.3%
2/61 • Number of events 2 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
General disorders
Fatigue
|
8.2%
5/61 • Number of events 5 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
General disorders
Lethargy
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Infections and infestations
IV site infection
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Nervous system disorders
Headache
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Nervous system disorders
Imbalance
|
18.0%
11/61 • Number of events 11 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Surgical and medical procedures
Numbness/Tingling
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Surgical and medical procedures
Headache
|
8.2%
5/61 • Number of events 5 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Surgical and medical procedures
Jaw pain
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Surgical and medical procedures
Edema
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Ear and labyrinth disorders
Imabalance
|
14.8%
9/61 • Number of events 9 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Surgical and medical procedures
Dysgnathia
|
3.3%
2/61 • Number of events 2 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Eye disorders
Vision problem
|
3.3%
2/61 • Number of events 2 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Musculoskeletal and connective tissue disorders
Fall
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Musculoskeletal and connective tissue disorders
Hemi-body muscle weakness
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Musculoskeletal and connective tissue disorders
Imbalance
|
3.3%
2/61 • Number of events 2 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal weakness
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Musculoskeletal and connective tissue disorders
Myoclonus
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Nervous system disorders
Ataxia
|
16.4%
10/61 • Number of events 10 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Nervous system disorders
Dysarthria
|
11.5%
7/61 • Number of events 7 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Nervous system disorders
Dysgeusia
|
9.8%
6/61 • Number of events 6 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Nervous system disorders
Dysmetria
|
11.5%
7/61 • Number of events 9 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Nervous system disorders
Gait disturbance
|
14.8%
9/61 • Number of events 9 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Nervous system disorders
Numbness/Tingling
|
32.8%
20/61 • Number of events 29 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Nervous system disorders
Slurred speech
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
|
Nervous system disorders
Unclear thinking
|
1.6%
1/61 • Number of events 1 • Intraprocedural cumulative through 5 Years
Intraprocedural, at ea. follow-up visit (1 Month, 3 Month, 6 Month, 12 Month and annually through Year 5
|
Additional Information
Nadir Alikacem, SVP Global Regulated Clinical Affairs
Insightec
Phone: 214-630-9900
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place