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ExAblate Transcranial MRgFUS of the Subthalamic Nucleus for Treatment of Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT02246374
Recruitment Status : Active, not recruiting
First Posted : September 22, 2014
Last Update Posted : August 10, 2018
Sponsor:
Information provided by (Responsible Party):
InSightec

Brief Summary:
This is primarily a safety protocol to evaluate the safety of subthalamotomy using Transcranial ExAblate for treatment of Parkinson's Disease (PD) motor features.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Device: ExAblate Transcranial System Not Applicable

Detailed Description:

This study is designed as a prospective, randomized, double-blind (to subjects and examiners), two-arm (ExAblate treated arm vs ExAblate Sham treated control arm) feasibility study. All treated subjects will be followed for 12 months.

Data will be collected to establish the basic safety and clinical efficacy of this type of treatment as the basis for later studies that will evaluate the full clinical efficacy.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Feasibility Clinical Trial of the Management of the Medically-Refractory Motor Symptoms of Advanced Idiopathic Parkinson's Disease With Unilateral Lesioning of the Subthalamic Nucleus Using the ExAblate Transcranial System
Study Start Date : September 2014
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ExAblate Treated Arm
ExAblate Transcranial System subthalamotomy for motor symptoms of Parkinson's Disease.
Device: ExAblate Transcranial System
ExAblate Transcranial System subthalamotomy for symptoms of Parkinson's Disease
Other Names:
  • MRgFUS
  • FUS
  • Focused Ultrasound
  • MR Guided Focused Ultrasound

Sham Comparator: ExAblate Sham Treated Arm
ExAblate Transcranial System sham subthalamotomy for motor symptoms of Parkinson's Disease. Sham subjects completing the 4 Month visit may be offered the actual ExAblate subthalamotomy.
Device: ExAblate Transcranial System
ExAblate Transcranial System subthalamotomy for symptoms of Parkinson's Disease
Other Names:
  • MRgFUS
  • FUS
  • Focused Ultrasound
  • MR Guided Focused Ultrasound




Primary Outcome Measures :
  1. Incidence and severity of adverse events [ Time Frame: Baseline to 4 months post treatment ]
    Safety will evaluate the incidence and severity of adverse events associated with ExAblate subthalamotomy for the treatment of Parkinson's Disease motor features.

  2. Mean change in MDS-UPDRS Part III scores [ Time Frame: Baseline to 4 months post treatment ]
    This is a feasibility trial with no hypothesis testing. Primary efficacy will be evaluated using basic summary statistics including comparison of between- and within-group differences in the mean change (from baseline to 4 months) of the motor MDS-UPDRS Part III score for the side contralateral to subthalamotomy in the off-medication condition.


Secondary Outcome Measures :
  1. Long Term Adverse Events Profile [ Time Frame: Baseline to 12- months post treatment ]
    Additional safety will be evaluated by follow up of adverse events through 12 months post treatment.


Other Outcome Measures:
  1. Mean change in MDS-UPDRS total score [ Time Frame: Baseline to 12- months post treatment ]
    Duration of outcomes will be further evaluated using the MDS-UPDRS total score

  2. Mean change in MDS-UPDRS Part IV scores [ Time Frame: Baseline to 12-months post treatment ]
    Long term impact of ExAblate transcranial pallidotomy will be further evaluated using the MPS-UPDRS Part IV scores



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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women, age 30 years and older
  2. Subjects who are able and willing to give informed consent and able to attend all study visits
  3. Subjects with a diagnosis of idiopathic PD by UK Brain Bank Criteria as confirmed by a movement disorder neurologist at the site
  4. Levodopa responsive as defined by at least a 30% reduction in MDS-UPDRS motor sub-scale in the ON vs OFF medication state
  5. Disabling motor clinical features not optimally controlled by an adequate medication prescription. An adequate medication prescription is defined as a therapeutic dose of each medication or the development of side effects as the medication dose is titrated
  6. Predominant disability from one side of the body (i.e unilateral or markedly asymmetric disease) as determined by movement disorders neurologist and neurosurgeon
  7. Subjects should be on a stable dose of all PD medications for 30 days prior to study entry
  8. Subthalamic nucleus is visible on MRI so that it can be targeted by the ExAblate device
  9. Subjects should have a Screening motor assessment of ≥ 35 while OFF medications on the MDS-UPDRS
  10. Subject is able to communicate sensations during the ExAblate Transcranial procedure

Exclusion Criteria:

  1. Hoehn and Yahr stage in the ON medication state of 2.5 or greater
  2. Presence of severe dyskinesia as noted by a score of 3 or 4 on questions 4.1 and 4.2 of the MDS-UPDRS
  3. Presence of other central neurodegenerative disease suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy, corticobasal syndrome, dementia with Lewy bodies, and Alzheimer's disease
  4. Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications
  5. Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia
  6. Presence of significant cognitive impairment defined as score ≤ 21 on the Montreal Cognitive Assessment (MoCA) or Mattis Dementia Rating Scale of 120 or lower
  7. 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
  8. 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
  9. Legal incapacity or limited legal capacity as determined by the neuropsychologist
  10. 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)
  11. 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
  12. Severe hypertension (diastolic BP > 100 on medication)
  13. History of or current medical condition resulting in abnormal bleeding and/or coagulopathy
  14. 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
  15. 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
  16. 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
  17. Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
  18. Significant claustrophobia that cannot be managed with mild medication
  19. Subjects who weigh more than the upper weight limit of the MR table and who cannot fit into the MR scanner
  20. Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment
  21. History of intracranial hemorrhage
  22. History of multiple strokes, or a stroke within past 6 months
  23. Subjects with a history of seizures within the past year
  24. Subjects with brain tumors
  25. Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment
  26. Are participating or have participated in another clinical trial in the last 30 days
  27. Any illness that in the investigator's opinion preclude participation in this study
  28. Subjects unable to communicate with the investigator and staff
  29. Pregnancy or lactation
  30. Subjects who have an overall Skull Density Ration lower than 0.40 as calculated from the screening CT

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02246374


Locations
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
InSightec
Investigators
Principal Investigator: Jeff Elias, MD University of Virginia

Responsible Party: InSightec
ClinicalTrials.gov Identifier: NCT02246374     History of Changes
Other Study ID Numbers: PD003
First Posted: September 22, 2014    Key Record Dates
Last Update Posted: August 10, 2018
Last Verified: August 2018

Keywords provided by InSightec:
Parkinson's Disease
ExAblate
MRgFUS

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases