This trial is active, not recruiting.

Condition parkinson's disease
Treatment high intensity focused ultrasound unilateral subthalamotomy
Phase phase 1
Sponsor Fundación de investigación HM
Collaborator Insightech
Start date April 2016
End date January 2017
Trial size 10 participants
Trial identifier NCT02912871, PD003E


Based on published animal and human studies, we believe ExAblate Transcranial subthalamotomy can be as safe and as effective as any of the surgical treatments within the currently accepted standard of care including radiofrequency lesioning and Deep Brain Stimulation (DBS). A unilateral lesion of the subthalamic nucleus has shown reduction of contralateral motor symptoms in Parkinson's disease (PD). Using ExAblate Transcranial Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU) to create the subthalamotomy has several potential advantages over current therapies including the fact that transcranial lesioning can be performed in a precise manner with simultaneous as well as continuous clinical and radiographic monitoring. If the potential of ExAblate Transcranial subthalamotomy can be realized, it could supplant radiofrequency and radiosurgery techniques and provide a viable alternative procedure for subjects considering DBS.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Subthalamotomy performed by High intensity focused ultrasound in a single session.
high intensity focused ultrasound unilateral subthalamotomy
Unilateral thermolesion in the Subthalamic nucleus performed by High Intensity Focused ultrasound

Primary Outcomes

All causes of morbidity
time frame: within the first 6 months (plus minus 1 month) after treatment
time frame: 6 months

Secondary Outcomes

time frame: 6 months
time frame: 6 months
time frame: 6 months
Dyskinesia severity as assessed through the Dyskinesia rating scale
time frame: 6 months
Levodopa equivalent medication usage (milligrams) when applicable
time frame: 6 months
Patient and Clinician Global Impression of Change
time frame: 6 months
Quality of life assessment with PDQ-39
time frame: 6 months

Eligibility Criteria

Male or female participants at least 30 years old.

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 through 6 Months 3. Subjects with a diagnosis of PD by United Kingdom Brain Bank Criteria as confirmed by a movement disorder neurologist at the site 4. Predominant disability from one side of the body (i.e unilateral or markedly asymmetric disease) as determined by a movement disorders neurologist 5. Subjects should be on a stable dose of all PD medications for 30 days prior to study entry, if possible. 6. Topographic coordinates of the subthalamic nucleus are localizable on Magnetic resonance imaging (MRI) so that it can be targeted by the ExAblate device. 7. 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 Movement Disorders Society-Unified Parkinson's Disease Rating Scale (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 Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) as manifested by one (or more) of the following occurring within the preceding 12-month period: - 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). - 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) - Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct) - 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: - Unstable angina pectoris on medication - Subjects with documented myocardial infarction within six months of protocol entry - Significant congestive heart failure defined with ejection fraction < 40 - Subjects with unstable ventricular arrhythmias - Subjects with atrial arrhythmias that are not rate-controlled 12. Severe hypertension (diastolic Blood Pressure > 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 international normalized ratio (INR) coagulation studies exceeding the institution's laboratory standard 16. Patient with severely impaired renal function with estimated glomerular filtration rate <30milliliter/minute/1.73m2 (or per local standards should that be more restrictive) and/or who is on dialysis; 17. Subjects with standard contraindications for MRI 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. Subject who weigh more than the upper weight limit of the MRI table and who cannot fit into the MRI 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 malignant brain tumors 25. Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment. 26. Any illness that in the investigator's opinion preclude participation in this study. 27. Subjects unable to communicate with the investigator and staff. 28. Pregnancy or lactation. 29. Subjects who have an Overall Skull Density Ratio (SDR) of 0.3 (±0.05) or less as calculated from the screening Cranial Tomography scan (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.

Additional Information

Official title A Pilot Clinical Trial of the Feasibility, Safety and Efficacy of Subthalamotomy Using the ExAblate Transcranial System to Treat the Cardinal Motor Features of Parkinson's Disease
Principal investigator Jose Obeso, MD, PhD
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Fundación de investigación HM.