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)

• ClinicalTrials.gov Identifier: NCT04728295
• Recruitment Status: Recruiting
• First Posted: January 28, 2021
• Last Update Posted: October 18, 2021
• Sponsor: InSightec
• Information provided by (Responsible Party): InSightec

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	Device: Exablate 4000	Not Applicable

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 8 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: This is a bilateral study. Subjects will be treated on one side of the brain and will be allowed to receive treatment on the other side if eligible.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: May 14, 2021
• Estimated Primary Completion Date: January 1, 2022
• Estimated Study Completion Date: January 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Part III OFF Medication [ Time Frame: Up to Month 3 post Bilateral Treatment ]
   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.

Secondary Outcome Measures :

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

Other Outcome Measures:

1. MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Part III OFF Medication [ Time Frame: Up to Month 12 post Bilateral Treatment ]
   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.
2. MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Part IV [ Time Frame: Up to Month 12 post Bilateral Treatment ]
   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.

Eligibility Criteria

• 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, desiring bilateral treatment option with second side staged at 6 months.
2. Subject is able and willing to give informed consent and able to attend all study visits
3. Subject with a diagnosis of idiopathic PD by UK Brain Bank Criteria as confirmed by a movement disorder neurologist at the site.
4. Subject has Levodopa responsive as defined by at least a 30% reduction in MDSUPDRS motor subscale in the ON vs OFF medication state.
5. Subject has MDS-UPDRS score of 30 or greater in the meds OFF condition.
6. Motor complications of PD on optimum medical treatment characterized dyskinesia (MDS-UPDRS item 4.2 score of 2 or greater in the meds ON condition) OR Motor fluctuations (MDS-UPDRS item 4.4 score of 2 or greater in the meds ON condition)
7. Subject is on a stable dose of all PD medications for 30 days prior to screening visit PD assessments as determined by medical records
8. Subject is able to communicate sensations during the Exablate procedure.
9. Subject's Pallido-thalamic region can be targeted by the Exablate device.

Exclusion Criteria:

1. Subject has a score of 3 or greater on the PULL test.
2. Subject with severe premorbid risks as specified in the MDS-UPDRS Part II subsection motor aspects of experiences of daily living scores: 3 or 4 on question 2.1 (speech) OR 3 or 4 on question 2.3 (chewing and swallowing) OR 4 on question 2.2 (saliva and drooling).
3. Subject where there is suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications.
4. Subject with significant cognitive impairment as determined by the neuropsychologist.
5. 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.
6. Subject with unstable psychiatric disease, defined as active uncontrolled depressive symptoms, psychosis, delusions, hallucinations, or suicidal ideation
7. Women of childbearing potential who are pregnant or lactating
8. Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse

9. 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

10. 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
11. 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.
12. 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.
13. Subjects with a history of seizures within the past year.
14. Subject with an intracranial brain tumor
15. 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.
16. Any illness that in the investigator's opinion preclude participation in this study.
17. Subject with standard contraindications for MR imaging such as implanted metallic devices
18. Subject who had prior deep brain stimulation of the basal ganglia or thalamus.
19. Subjects who are unable to tolerate the required prolonged stationary supine position during treatment.
20. Subjects who have an Overall Skull Density Ratio of less than 0.40 as calculated from the screening CT.
21. Subject who is participating in another clinical investigation with an active treatment arm in the last 30 days.
22. Subject who is unable to communicate with the investigator and staff. Additional Exclusion Criteria for Staged Bilateral PTT procedure
23. Subject who had moderate to severe neurological event such as dysphagia, speech, gait imbalance, cognitive impairment, and visual field deficit following index procedure.

Contacts and Locations

Contacts

Contact: Gaganjot Sooch; 214-630-2000; gaganjots@insightec.com

Locations

United States, California

Stanford; Recruiting

Palo Alto, California, United States, 94304

Contact: Bharati Sanjanwala 650-721-2830 bharatis@stanford.edu

Principal Investigator: Vivek Buch, MD

United States, Maryland

University of Maryland, Baltimore; Recruiting

Baltimore, Maryland, United States, 21201

Contact: Kaitlyn Henry 410-328-0939 khenry@som.umaryland.edu

Principal Investigator: Howard Eisenberg, MD

Sub-Investigator: Paul Fishman, MD

United States, New York

New York University Langone; Recruiting

New York, New York, United States, 10016

Contact: Cathryn Lapierre Cathryn.lapierre@nyulangone.org

Principal Investigator: Alon Mogilner, MD

Weill Cornell Medicine; Recruiting

New York, New York, United States, 10065

Contact: Rachael Olovyannikov 212-746-7373 rao4005@med.cornell.edu

Contact: Blagovest Nikolov 212-746-9882 Bln2001@med.cornell.edu

Principal Investigator: Michael Kaplitt, MD

Sub-Investigator: Harini Sarva, MD

Taiwan

Chang Bing Show Chwan Memorial Hospital; Recruiting

Lugang, Changhua County, Taiwan

Contact: Wei Chieh Chang, MD changweichieh@gmail.com

Contact: Yen-Hui Yang :+886-4-7813888 ext 70379 irene.yang71917@gmail.com

Sponsors and Collaborators

InSightec

More Information

• Responsible Party: InSightec
• ClinicalTrials.gov Identifier: NCT04728295
• Other Study ID Numbers: PD014
• First Posted: January 28, 2021
• Last Update Posted: October 18, 2021
• Last Verified: May 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by InSightec:

Exablate; MRgFUS; Pallidothalamic Tract

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases