ExAblate Pallidotomy for Medically-Refractory Dyskinesia Symptoms or Motor Fluctuations of Advanced Parkinson's Disease

A Pivotal Clinical Trial of the Management of the Medically-Refractory Dyskinesia Symptoms or Motor Fluctuations of Advanced Idiopathic Parkinson's Disease With Unilateral Lesioning of the Globus Pallidum Using the ExAblate Neuro System

Evaluate the safety and efficacy of unilateral focused ultrasound pallidotomy using the ExAblate 4000 System in the management of dyskinesia symptoms or motor fluctuations for medication refractory, advanced idiopathic Parkinson's disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: ExAblate Pallidotomy; Device: Sham ExAblate Pallidotomy

Detailed Description

The goal of this prospective, two-arm, sham-controlled, randomized, multi-center pivotal study is to evaluate the safety and efficacy of unilateral focused ultrasound pallidotomy using the ExAblate 4000 System in the management of dyskinesia symptoms or motor fluctuations for medication refractory, advanced idiopathic Parkinson's disease.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care
• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Neurological Institute Carlo Besta
  • Verona, Italy, 37134
    • Azienda Ospedaliera Universitaria di Verona, Univerista di Verona
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
• Spain
  • Madrid
    • Móstoles, Madrid, Spain, 28938
      • CINAC-Hospital HM Puerta del Sur
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
• Taiwan
  • Changhua, Taiwan
    • Chang Bing Show Chwan Memorial Hospital
• United Kingdom
  • London, United Kingdom
    • St. Mary's Hospital
• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Palm Beach Neuroscience Institute/Sperling Medical Group
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical System
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • New York, New York, United States, 10016
      • New York University Health Langone
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Hospital Department of Neurosurgery
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 12 Months.
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 subscale in the ON vs OFF medication state.
5. MDS-UPDRS score of ≥ 20 in the meds OFF condition OR Motor complications of PD on optimum medical treatment .
6. Subjects should be on a stable dose of all PD medications for 30 days prior to study entry as determined by medical records.
7. Subject is able to communicate sensations during the ExAblate procedure.
8. Subjects on stable antidepressant medications for at least 3 months

Exclusion Criteria:

1. Hoehn and Yahr stage in the ON medication state of 3 or greater.
2. 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.
3. Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications.
4. Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia.
5. Presence of significant cognitive impairment using MMSE ≤ 24.
6. Unstable psychiatric disease, defined as active uncontrolled depressive symptoms, psychosis, delusions, hallucinations, or suicidal ideation.
7. Subjects with an active alcohol or drug dependency or history of drug/alcohol abuse within the past year
8. Subjects with unstable cardiac status
9. Severe hypertension (diastolic BP > 100 on medication).
10. Current medical condition resulting in abnormal bleeding and/or coagulopathy.
11. 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.
12. 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
13. Patient with kidney disease or on dialysis.
14. Subjects with standard contraindications for MR imaging
15. Significant claustrophobia that cannot be managed with mild medication.
16. Subjects who weigh more than the upper weight limit of the MR scanner table and who cannot fit into the MR scanner.
17. Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment.
18. History of intracranial hemorrhage, multiple strokes, or a stroke within past 6 months.
19. Subjects with a history of seizures within the past year.
20. Subjects with brain tumors.
21. Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment.
22. Are participating or have participated in another clinical trial in the last 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ExAblate Pallidotomy; ExAblate treatment for Advanced Idiopathic Parkinson's Disease	Device: ExAblate Pallidotomy; ExAblate Pallidotomy for Parkinson's Disease; Other Names: MRgFUS; Pallidotomy
Sham Comparator: Sham ExAblate Pallidotomy; Sham (fake) treatment	Device: Sham ExAblate Pallidotomy; ExAblate MRgFUS Sham Procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder Analysis	Responder is defined as the patient reaching a minimally clinically significant difference on: 1. UDysRS (this measures dyskinesia and their impact) OR 2. MDS-UPDRS Part III Motor Exam -Total score (this measures overall motor fluctuations).	Change in UDysRS and MDS-UPDRS Part III Motor Exam score from before treatment to 3 months following treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Device and Procedure related complications	To evaluate of the incidence and severity of device- and procedure-related	At the time of ExAblate Pallidotomy procedure

Collaborators and Investigators

• Sponsor: InSightec

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2018
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: October 19, 2017
• First Submitted That Met QC Criteria: October 23, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: MRgFUS; ExAblate; Pallidotomy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Dyskinesias
• Other Study ID Numbers: PD006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes