Evaluation of the Safety and Effectiveness of Bilateral Exablate Ablation of the Pallidothalamic Tract (PTT) for the Treatment of the Motor Complications of Parkinson's Disease (PD)

Evaluate the Safety and Effectiveness of Staged Bilateral Exablate Ablation of the Pallidothalamic Tract (PTT) for the Treatment of the Motor Complications of Parkinson's Disease (PD).

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: Exablate 4000

Detailed Description

This study is a prospective, open label, single-arm, multi-center clinical trial to establish the safety and effectiveness of bilateral PTTractotomy for the treatment of motor complications in patients with bilateral idiopathic Parkinson's Disease. A maximum of 50 subjects will be treated at up to 10 sites.

Subjects will undergo an Exablate index procedure targeting the PTT and will be seen at 1-week,1-, 3-, and 6- months post treatment. At the 6-month visit, subjects will be evaluated for an Exablate procedure on the other side.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain
    • Neurology, Hospital Universitario HM Puerta del Sur (HM CINAC)
  • Pamplona, Spain
    • Clinica Universidad de Navarra
• Taiwan
  • Changhua County
    • Lugang, Changhua County, Taiwan
      • Chang Bing Show Chwan Memorial Hospital
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford
  • Florida
    • Delray Beach, Florida, United States, 33484
      • Delray Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • New York, New York, United States, 10016
      • New York University Langone

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Men and women, age 30 years and older, desiring bilateral treatment option with second side staged at 6 months.
• Subject is able and willing to give informed consent and able to attend all study visits
• Subject with a diagnosis of idiopathic PD by UK Brain Bank Criteria as confirmed by a movement disorder neurologist at the site.
• Motor complications of PD on optimum medical treatment
• Subject is on a stable dose of all PD medications for 30 days prior to screening visit
• Subject is able to communicate sensations during the Exablate procedure.

Exclusion Criteria:

• Subject where there is suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications.
• Subject with significant cognitive impairment as determined by the neuropsychologist.
• Subject has 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.
• Subject with unstable psychiatric disease, defined as active uncontrolled depressive symptoms, psychosis, delusions, hallucinations, or suicidal ideation
• Women of childbearing potential who are pregnant or lactating
• Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse

• Subject with unstable cardiac status or severe hypertension including:

  • Documented myocardial infarction within six months of enrollment
  • Unstable angina on medication
  • Unstable or worsening congestive heart failure
  • Left ventricular ejection fraction below the lower limit of normal
  • History of a hemodynamically unstable cardiac arrhythmia
  • Cardiac pacemaker
  • Diastolic BP > 100 on medication
• Subject with history of abnormal bleeding, hemorrhage, or coagulopathy including:
• Subject 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, multiple strokes, or a stroke within past 6 months
• Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment
• Subject is 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.
• Subject 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 a history of seizures within the past year.
• Subject with an intracranial brain tumor
• Subjects with life-threatening systemic disease that include and not limited to the following will be excluded from the study participation: HIV, liver failure, blood dyscrasias, etc.
• Any illness that in the investigator's opinion preclude participation in this study.
• Subject with standard contraindications for MR imaging such as implanted metallic devices
• Subject who had prior deep brain stimulation of the basal ganglia or thalamus.
• Subjects who are unable to tolerate the required prolonged stationary supine position during treatment.
• Subject who is participating in another clinical investigation with an active treatment arm in the last 30 days.
• Subject who is unable to communicate with the investigator and staff.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exablate Pallidothalamic Tractotomy; Exablate treatment for Advanced Idiopathic Parkinson's Disease	Device: Exablate 4000; Exablate Pallidothalamic Tractotomy; Other Names: MRgFUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Part III OFF Medication	OFF-medication, Upper + Lower Extremity motor score from the MDS-UPDRS Part III comparing Month 3 post Bilateral treatment to Baseline. Lower score on the scale means a better outcome.	Up to Month 3 post Bilateral Treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Part II	MDS-UPDRS Part II - Activities of Daily living comparing all Bilateral scheduled visits to Baseline. Lower score on the scale means a better outcome.	Up to Month 12 post Bilateral Treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Part III OFF Medication	OFF-medication, Upper + Lower Extremity motor score from the MDS-UPDRS Part III comparing all visits post Bilateral treatment to Baseline. Lower score on the scale means a better outcome.	Up to Month 12 post Bilateral Treatment
MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Part IV	MDS-UPDRS Part IV at all Bilateral visits comparing all visits post Bilateral treatment to Baseline. Lower score on the scale means a better outcome.	Up to Month 12 post Bilateral Treatment

Collaborators and Investigators

• Sponsor: InSightec

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: January 14, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: MRgFUS; Exablate; Pallidothalamic Tract
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: PD014

Drug and device information, study documents

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