Clinical trial NCT02263885: ExAblate Transcranial MRgFUS of the Globus Pallidum for Treatment of Parkinson's Disease
Official title: A Feasibility Clinical Trial of the Management of the Medically-Refractory Dyskinesia Symptoms of Advanced Idiopathic Parkinson's Disease With Unilateral Lesioning of the Globus Pallidum Using the ExAblate Transcranial System
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
ExAblate
MRgFUS
Lead sponsor: InSightec
Sponsor class: INDUSTRY
First posted: 2014-10-13
Enrollment: 20
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The proposed study will evaluate the safety, and initial efficacy of using the ExAblate Transcranial to create a unilateral lesion in the globus pallidus as an adjunct to PD medications in subjects who are over 30 years of age and considered medication-refractory with advanced idiopathic Parkinson's disease (PD).

Detailed description: The purpose of this study is to evaluate the safety and initial clinical effectiveness of ExAblate Transcranial unilateral thermal ablation of the globus pallidus of subjects suffering from medication-refractory, advanced idiopathic PD.

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.

Eligibility criteria: 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 24 Months
* Subjects with a diagnosis of idiopathic PD
* Levodopa responsive as defined by at least a 30% reduction in MDS-UPDRS motor subscale in the ON vs OFF medication state.
* Disabling motor complications of PD on optimum medical treatment
* Predominant disability from one side of the body (i.e unilateral or markedly asymmetric disease) as determined by movement disorders neurologist and neurosurgeon
* 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:

* 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.
* Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications.
* Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia
* 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.
* Legal incapacity or limited legal capacity as determined by the neuropsychologist
* Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse
* 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
* Severe hypertension (diastolic BP \> 100 on 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 (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
* 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;
* 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.
* Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment.
* History of intracranial hemorrhage
* History of multiple strokes, or a stroke within past 6 months
* 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.
* Are participating or have participated in another clinical trial in the last 30 days
* Any illness that in the investigator's opinion preclude participation in this study.
* Subjects unable to communicate with the investigator and staff.
* Pregnancy or lactation.

Primary outcomes:
measure: Adverse Events
timeFrame: Month 24
Secondary outcomes:
measure: Unified Dyskinesia Rating Scale Total Score.
timeFrame: Screening, Month 3, Month 6, Month 12, Month 24
measure: Unified Dyskinesia Rating Scale (UDysRS), Part III
timeFrame: Screening, Month 3, Month 6, Month 12, Month 24
measure: Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III Motor Exam
timeFrame: Screening, Month 3, Month 6, Month 12, Month 24
measure: Mood Disorders Society - Unified Parkinson's Disease Rating Scale Part II
timeFrame: Screening, Month 3, Month 6, Month 12, Month 24
measure: Mood Disorder Society Unified Parkinson's Disease Rating Scale Part IV
timeFrame: Screening, Month 3, Month 6, Month 12, Month 24
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Baltimore
country: United States
facility: University of Maryland Medical System
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Columbus
country: United States
facility: The Ohio State Wexner Medical Center
state: Ohio
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
References:
citation: Eisenberg HM, Krishna V, Elias WJ, Cosgrove GR, Gandhi D, Aldrich CE, Fishman PS. MR-guided focused ultrasound pallidotomy for Parkinson's disease: safety and feasibility. J Neurosurg. 2020 Nov 27;135(3):792-798. doi: 10.3171/2020.6.JNS192773. Print 2021 Sep 1.