Parkinson's Disease
Conditions
Keywords
ExAblate Transcranial MRgFUS
Brief summary
This is a feasibility study to evaluate the safety and initial effectiveness of unilateral ExAblate thermal ablation of the Vim thalamic nucleus of subjects suffering from medication-refractory, idiopathic, tremor-dominant PD, using the ExAblate Transcranial system compared to a Sham Vim thalamotomy procedure. Data will be collected to establish the basic safety of this type of treatment as the basis for later studies that will evaluate its full clinical efficacy. The Sham treatment data will be used to evaluate placebo effect from treatment.
Detailed description
Subjects who sign informed consent and pass all eligibility criteria will be randomized to a treatment assignment. During treatment, the assigned treatment (ExAblate Transcranial or Sham ExAblate Transcranial)will be delivered. Subjects are followed in a blinded fashion for three (3) months. After the 3-month assessment, subjects will be unblinded and told their treatment assignment. Subjects receiving Sham ExAblate Transcranial treatment who still meet criteria will be crossed over and receive an active ExAblate Transcranial treatment. Subjects will be followed for up to two (2) years. Follow-up at 1 week, 1 month, 3 months, 6 months, 9 months, 12 months and up to two (2) years includes Unified Parkinson's Disease Rating Scale (UPDRS) scoring, mental and cognitive functional testing and questionnaires.
Interventions
DEVICEExAblate Transcranial MRgFUS
ExAblate Transcranial MR Guided Focused Ultrasound
DEVICESham ExAblate Transcranial MRgFUS
Sham ExAblate Transcranial MR Guided Focused Ultrasound
Sponsors
InSightec
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Single factor. ExAblate test verses ExAblate placebo randomized 2:1.
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women, age 30 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 idiopathic PD as confirmed from clinical history and examination by a movement disorder neurologist at the site * Subject demonstrates a severe resting tremor or postural/action as measured by UPDRS * Subject exhibits a significant disability from their PD tremor despite medical treatment * Subjects should be on a stable dose of all PD 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 * Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse * 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 * Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment * Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | Month 3 | Evaluate of adverse events (AEs) associated with the ExAblate Transcranial thalamotomy of medication-refractory, tremor-dominant PD during the ExAblate treatment. Primary safety analyses are reported in the adverse events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tremor Motor Score Percent Change From Baseline. | Baseline, Month 3 | 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). |
| Tremor Motor Scores - Clinical Rating Scale for Tremor - Treated Side Upper Extremity Parts A & B. | Baseline, Month 3, Month 12 | Upper extremity Tremor-Motor score for the treated side is a sub-scale of Clinical Rating Scale for Tremor (CRST) Part A and Part B sum that measures treated-side upper extremity tremor changes over time. Tremor-motor scores range from 0-32 points for each side with lower scores being a better outcome. Subject's Tremor-Motor scores for the test and sham control groups were averaged at each study visit. |
| Functional Disabilities - Clinical Rating Scale for Tremor Part C - Functional Disabilities | Baseline, Month 3, Month 12 | The Clinical Rating Scale for Tremor (CRST) Part C is a measure of functional disability due to tremor. The Clinical Rating Scale for Tremor Part C consists of 8 items each scored from 0 to 4. Thus, the total score summed ranges from 0 to 32 and provides an overall assessment of activities of daily living. Low scores on the Clinical Rating Scale for Tremor (CRST) Part C are better. Low scores show improvement in functional disabilities compared to higher scores. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ExAblate Transcranial MRgFUS ExAblate Transcranial MR guided Focused Ultrasound
ExAblate Transcranial MRgFUS: ExAblate Transcranial MR Guided Focused Ultrasound | 20 |
| Sham ExAblate Transcranial MRgFUS Sham treatment with ExAblate MR guided Focused Ultrasound
Sham ExAblate Transcranial MRgFUS: Sham ExAblate Transcranial MR Guided Focused Ultrasound | 7 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Alternative Treatment | 2 | 0 |
| Overall Study | Health Concerns Unrelated to Study | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | ExAblate Transcranial MRgFUS | Sham ExAblate Transcranial MRgFUS | Total |
|---|---|---|---|
| Age, Continuous | 67.9 years STANDARD_DEVIATION 9.6 | 62.9 years STANDARD_DEVIATION 11.3 | 66.6 years STANDARD_DEVIATION 10.1 |
| Clinical Rating Scale for Tremor - Treated Side | 19.0 units on a scale STANDARD_DEVIATION 8.7 | 20.1 units on a scale STANDARD_DEVIATION 7.4 | 19.3 units on a scale STANDARD_DEVIATION 8.3 |
| Mean Unified Parkinson's Disease Rating Scale (UPDRS) #20 | 3.7 units on a scale STANDARD_DEVIATION 1 | 3.4 units on a scale STANDARD_DEVIATION 1.5 | 3.6 units on a scale STANDARD_DEVIATION 1.1 |
| Mean Unified Parkinson's Disease Rating Scale (UPDRS) #21 | 3.2 units on a scale STANDARD_DEVIATION 1.3 | 3.6 units on a scale STANDARD_DEVIATION 1.1 | 3.3 units on a scale STANDARD_DEVIATION 1.2 |
| Race/Ethnicity, Customized Race Black | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Caucasian | 18 Participants | 6 Participants | 24 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 20 participants | 7 participants | 27 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 19 Participants | 7 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 7 |
| other Total, other adverse events | 20 / 20 | 5 / 7 |
| serious Total, serious adverse events | 3 / 20 | 1 / 7 |
Outcome results
Primary
Number of Adverse Events
Evaluate of adverse events (AEs) associated with the ExAblate Transcranial thalamotomy of medication-refractory, tremor-dominant PD during the ExAblate treatment. Primary safety analyses are reported in the adverse events module.
Time frame: Month 3
Population: All Adverse Events are reported in the Adverse Events module.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ExAblate Transcranial MRgFUS | Number of Adverse Events | 100 Number of Adverse Events |
| Sham ExAblate Transcranial MRgFUS | Number of Adverse Events | 10 Number of Adverse Events |
Secondary
Functional Disabilities - Clinical Rating Scale for Tremor Part C - Functional Disabilities
The Clinical Rating Scale for Tremor (CRST) Part C is a measure of functional disability due to tremor. The Clinical Rating Scale for Tremor Part C consists of 8 items each scored from 0 to 4. Thus, the total score summed ranges from 0 to 32 and provides an overall assessment of activities of daily living. Low scores on the Clinical Rating Scale for Tremor (CRST) Part C are better. Low scores show improvement in functional disabilities compared to higher scores.
Time frame: Baseline, Month 3, Month 12
Population: The Exablate sham subjects exited the study at the Month 3 visit. The Exablate test subjects continued on through Month 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ExAblate Transcranial MRgFUS | Functional Disabilities - Clinical Rating Scale for Tremor Part C - Functional Disabilities | Baseline | 14.1 score on a scale | Standard Deviation 5.7 |
| ExAblate Transcranial MRgFUS | Functional Disabilities - Clinical Rating Scale for Tremor Part C - Functional Disabilities | Month 3 | 6.4 score on a scale | Standard Deviation 6.6 |
| ExAblate Transcranial MRgFUS | Functional Disabilities - Clinical Rating Scale for Tremor Part C - Functional Disabilities | Month 12 | 6.9 score on a scale | Standard Deviation 7.2 |
| Sham ExAblate Transcranial MRgFUS | Functional Disabilities - Clinical Rating Scale for Tremor Part C - Functional Disabilities | Month 12 | NA score on a scale | — |
| Sham ExAblate Transcranial MRgFUS | Functional Disabilities - Clinical Rating Scale for Tremor Part C - Functional Disabilities | Baseline | 16.7 score on a scale | Standard Deviation 3.9 |
| Sham ExAblate Transcranial MRgFUS | Functional Disabilities - Clinical Rating Scale for Tremor Part C - Functional Disabilities | Month 3 | 14.6 score on a scale | Standard Deviation 4.2 |
Secondary
Tremor Motor Score 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, Month 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ExAblate Transcranial MRgFUS | Tremor Motor Score Percent Change From Baseline. | 51.9 percent change from baseline | Standard Deviation 33.4 |
| Sham ExAblate Transcranial MRgFUS | Tremor Motor Score Percent Change From Baseline. | 12.7 percent change from baseline | Standard Deviation 25.7 |
Secondary
Tremor Motor Scores - Clinical Rating Scale for Tremor - Treated Side Upper Extremity Parts A & B.
Upper extremity Tremor-Motor score for the treated side is a sub-scale of Clinical Rating Scale for Tremor (CRST) Part A and Part B sum that measures treated-side upper extremity tremor changes over time. Tremor-motor scores range from 0-32 points for each side with lower scores being a better outcome. Subject's Tremor-Motor scores for the test and sham control groups were averaged at each study visit.
Time frame: Baseline, Month 3, Month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ExAblate Transcranial MRgFUS | Tremor Motor Scores - Clinical Rating Scale for Tremor - Treated Side Upper Extremity Parts A & B. | Month 12 | 10.5 score on a scale | Standard Deviation 10.2 |
| ExAblate Transcranial MRgFUS | Tremor Motor Scores - Clinical Rating Scale for Tremor - Treated Side Upper Extremity Parts A & B. | Baseline | 19.0 score on a scale | Standard Deviation 8.7 |
| ExAblate Transcranial MRgFUS | Tremor Motor Scores - Clinical Rating Scale for Tremor - Treated Side Upper Extremity Parts A & B. | Month 3 | 9.6 score on a scale | Standard Deviation 9.7 |
| Sham ExAblate Transcranial MRgFUS | Tremor Motor Scores - Clinical Rating Scale for Tremor - Treated Side Upper Extremity Parts A & B. | Baseline | 20.1 score on a scale | Standard Deviation 7.4 |
| Sham ExAblate Transcranial MRgFUS | Tremor Motor Scores - Clinical Rating Scale for Tremor - Treated Side Upper Extremity Parts A & B. | Month 3 | 17.4 score on a scale | Standard Deviation 7.8 |
| Sham ExAblate Transcranial MRgFUS | Tremor Motor Scores - Clinical Rating Scale for Tremor - Treated Side Upper Extremity Parts A & B. | Month 12 | NA score on a scale | — |