Tracking Information

First Submitted Date ^ICMJE

January 7, 2019

First Posted Date ^ICMJE

June 28, 2019

Last Update Posted Date

June 28, 2019

Actual Study Start Date ^ICMJE

February 6, 2017

Estimated Primary Completion Date

August 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Clinical Rating Scale for Tremor [ Time Frame: 3 Months after Treatment ]
Primary effectiveness will be a comparison of the CRST scores at baseline vs. 3 months. (Range 0-152, scores are combined, the higher the score, the greater the clinical level of tremor, the worse clinical outcome is)
Severity of Device and Procedure related complications [ Time Frame: 1 year ]
To evaluate the incidence and severity of adverse events (AEs) associated with the ExAblate Transcranial thalamotomy of medication-refractory, tremor dominant PD after the ExAblate treatment and during the follow-up period of up up to 1 year

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

No Changes Posted

Current Secondary Outcome Measures ^ICMJE

Clinical Rating Scale for Tremor, Total Score [ Time Frame: 1 year ]
On-medication, total tremor (CRST) score (Range 0-152, scores are combined, the higher the score, the greater the clinical level of tremor, the worse clinical outcome is)
Clinical Rating Scale for Tremor, Part C [ Time Frame: 1 year ]
Level of disability measured from Part C subsection of CRST - Subcore of sections 16 to 23 (Range 0-32, scores are combined, the higher the scub-score, the greater the level of subject's disability, the worse clinical outcome is)
Parkinson's Disease Questionnaire - 39 [ Time Frame: 1 year ]
Quality of life assessment with PDQ-39 (Range 0-156, scores are combined, the higher the score, the greater the level of clinical expression of Parkinson Disease, the worse clinical outcome is)

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

Safety and Initial Effectiveness of Transcranial MR Guided Focused Ultrasound for the Treatment of Parkinson's Disease

Official Title ^ICMJE

A Feasibility Study to Evaluate Safety and Initial Effectiveness of ExAblate Transcranial MR Guided Focused Ultrasound for Unilateral Thalamotomy in the Treatment of Medication-Refractory Tremor Dominant Idiopathic Parkinson's Disease

Brief Summary

Safety and Effectiveness in ExAblate Neuro treatment of medication-refractory tremor in subjects with idiopathic Parkinson's disease.

Detailed Description

The goal of this prospective, single-arm, multi-site, feasibility study is to develop data to evaluate the safety and effectiveness of unilateral focused ultrasound thalamotomy using this ExAblate Transcranial System in the treatment of medication-refractory tremor resulting from idiopathic Parkinson's disease.

The Indications for Use claim for this system is: treatment of medication-refractory tremor in subjects with idiopathic Parkinson's disease.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Not Applicable

Study Design ^ICMJE

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

ExAblate Neuro Treatment Group

Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Parkinson Disease

Intervention ^ICMJE

Device: ExAblate Neuro Thalamotomy Treatment

Non-invasive Focused Ultrasound Ablation of Thalamus Vim nucleus using ExAblate MRgFUS system for treatment Tremor Dominant Parkinson Disease

Other Names:

MRgFUS Vim ablation
Non-invasive Focused Ultrasound Ablation of Thalamus Vim nucleus

Study Arms ^ICMJE

Experimental: ExAblate MRgFUS treatment

Ablation of Thalamus Vim nucleus with ExAblate 4000 Neuro MRgFUS for TDPD

Intervention: Device: ExAblate Neuro Thalamotomy Treatment

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Unknown status

Estimated Enrollment ^ICMJE

50

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date ^ICMJE

December 31, 2020

Estimated Primary Completion Date

August 30, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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 through 3 Months
Subjects with a diagnosis of idiopathic PD as confirmed from clinical history and examination by a movement disorder neurologist at the site
All subjects included in this study will have a TD/PIGD ratio > 1.15 in the medicated [ON] state as calculated from the UPDRS formula as described by S, et. al., [74].

Note: Ratios for TD/PIGD that are greater than or equal to 1.15 are defined as TDPD. PIGD includes those with a ratio of less than or equal to 0.9. Scores of greater than 0.9 and less than 1.15 are considered a mixed subtype.
Subject demonstrates a resting tremor severity score of greater than or equal to 3 in the hand/arm as measured by the medicated (ON) MDS-UPDRS question 3.17 or a postural/action tremor greater than or equal to a 2 for question 3.15 or 3.16.
Significant disability due to PD tremor despite medical treatment (CRST score of 2 or above in any one of the items 16-23 from the Disability subsection of the CRST: [speaking, feeding other than liquids, bringing liquids to mouth, hygiene, dressing, writing, working, and social activities])
Tremor remains disabling when medical therapy is optimal or not tolerated for the treatment of other cardinal signs of PD (bradykinesia, rigidity, etc), as determined by a movement disorders neurologist at the site
Subjects should be on a stable dose of all PD medications for 30 days prior to study entry.
The thalamus must be apparent on MRI such that targeting of the Vim nucleus can be performed indirectly by measurement from a line connecting the anterior and posterior commissures of the brain.
Subject is able to communicate sensations during the ExAblate Transcranial procedure.

Exclusion Criteria:

Subjects with unstable cardiac status including:
1. Unstable angina pectoris on medication
2. Subjects with documented myocardial infarction within six months of protocol entry
3. Significant congestive heart failure defined with ejection fraction < 40
4. Subjects with unstable ventricular arrhythmias
5. Subjects with atrial arrhythmias that are not rate-controlled
Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse as defined by the criteria outlined in the DSM-IV as manifested by one (or more) of the following occurring within the preceding 12 month period:
1. Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (such as repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; or neglect of children or household).
2. Recurrent substance use in situations in which it is physically hazardous (such as driving an automobile or operating a machine when impaired by substance use)
3. Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct)
4. Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (for example, arguments with spouse about consequences of intoxication and physical fights).
Severe hypertension (diastolic BP > 100 on medication)
Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
Significant claustrophobia that cannot be managed with mild medication.
Current medical condition resulting in abnormal bleeding and/or coagulopathy
Patient with severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 (or per local standards should that be more restrictive) and/or who is on dialysis;
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 (e.g. Avastin) within one month of focused ultrasound procedure
Subjects with risk factors for intraoperative or postoperative bleeding as indicated by: platelet count less than 100,000 per cubic millimeter, a documented clinical coagulopathy, or INR coagulation studies exceeding the institution's laboratory standard
History of intracranial hemorrhage
History of multiple strokes, or a stroke within past 6 months
Subject who weigh more than the upper weight limit of the table or subjects who will not fit into the MR scanner
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.
Presence of central neurodegenerative disease, including but not limited to Parkinson-plus syndromes, suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy, corticobasal syndrome, dementia with Lewy bodies, and Alzheimer's disease.
Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications.
Presence of significant cognitive impairment as determined with a score ≤ 24 on the Mini Mental Status Examination (MMSE)
Unstable psychiatric disease, defined as active uncontrolled depressive symptoms, psychosis, delusions, hallucinations, or suicidal ideation. Subjects with stable, chronic anxiety or depressive disorders may be included provided their medications have been stable for at least 60 days prior to study entry and if deemed appropriately managed by the site neuropsychologist
Subjects with significant depression as determined following a comprehensive assessment by a neuropsychologist. Significant depression is being defined quantitatively as a score of greater than 14 on the Beck Depression Inventory.
Legal incapacity or limited legal capacity as determined by the neuropsychologist
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.
Any illness that in the investigator's opinion preclude participation in this study.
Pregnancy or lactation.
Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia
Subjects with remarkable atrophy and poor healing capacity of the scalp (> 30% of the skull area traversed by the sonication pathway) will be excluded from this study
Subjects who have an Overall Skull Density Ratio of 0.30 (±0.05) or less as calculated from the screening CT.
- It should be noted that for those candidates whose SDR ratio score is within the standard deviation, full technical assessment should be performed and reviewed by study investigator with the support of the sponsor.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

30 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

No

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

China, Japan

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04002596

Other Study ID Numbers ^ICMJE

PD001J

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:

No

Responsible Party

InSightec

Study Sponsor ^ICMJE

InSightec

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Martin Bernstein

InSightec

PRS Account

InSightec

Verification Date

June 2019

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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Safety and Initial Effectiveness of Transcranial MR Guided Focused Ultrasound for the Treatment of Parkinson's Disease (TDPD)

study details

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