MR-guided Focused Ultrasound Plus GCase

A Phase I/II Study for Bilateral Putamenal Delivery of Recombinant Glucocerebrosidase in Patients With Parkinson's Disease Using MR-guided Focused Ultrasound Induced Opening of the Blood-brain Barrier

The goal of this study is to establish safety and feasibility of intracerebral delivery of GCase via MRgFUS. This technique may offer potential benefits given the exposure of the putamen to GCase in animal models has been shown to be efficacious in improving Parkinson's disease pathology and phenotype.

Study Overview

• Status: Recruiting
• Conditions: Parkinsons Disease
• Intervention / Treatment: Device: Blood Brain Barrier Disruption - Functional

Detailed Description

This is a two-arm, open-label, intervention only phase I/II clinical study. One arm of the study will enroll seven (7) GBA PD patients and the other arm seven (7) idiopathic PD patients. During the intervention phase, the first four subjects of each arm will receive three transcranial bilateral putamenal GCase at 30 IU/kg IV every two weeks, followed by 60 IU/kg in the next three subjects. Following three treatments in this study, the subjects will be followed for twelve months.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alyssa Voelker-Christy; Phone Number: +1-817-948-5219; Email: alyssav@insightec.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Recruiting
      • Sunybrook Research Institute
      • Contact: Inthuja Suthananthan; Phone Number: 647-687-8062; Email: inthuja.suthananthan@sri.utoronto.ca
      • Principal Investigator: Nir Lipsman, M.D., Neurosurgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women between age 35 and 80 years, inclusive.
• Able and willing to give informed consent.
• Diagnosis of PD satisfying MDS Clinical Diagnostic Criteria for PD
• At least 2 years from initial diagnosis
• Hoehn and Yahr Stage 1-3 on PD medication
• Dopaminergic deficit by a positive DAT SPECT scan
• On stable regimen of PD medications for at least 90 days prior to the study
• American Society of Anesthesiologists (ASA) score 1-3
• Harbor at least one GBA mutation if enrolled in the GBA PD arm or two wild-type GBA alleles if enrolled in the idiopathic PD arm

Exclusion Criteria:

• Positive pregnancy test (for pre-menopausal women).
• Contraindication to DEFINITY ultrasound contrast agent or perflutren (e.g. hypersensitivity, known left or bidirectional cardiac shunt)
• Contraindication to MRI or gadolinium-DTPA (e.g. incompatible device, hypersensitivity)
• Insulin-dependent diabetes mellitus that is not well-controlled or that in the Investigator's opinion precludes participation in the study.
• Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 and/or on dialysis.
• Currently participating in another clinical therapeutic trial
• Patient receiving bevacizumab (Avastin) therapy
• Subjects with evidence of cranial or systemic infection.
• Cerebral or systemic vasculopathy.
• Documented cerebral infarction within the past 12 months or TIA in the past 1 month.
• Contraindication to GCase enzyme therapy, specifically previous hypersensitivity reaction to GCase enzyme therapy
• Parkinsonism plus symptoms, secondary parkinsonism
• Previous neurosurgical procedure for PD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Idiopathic PD Patients; Idiopathic PD patients receiving 3 cycles of BBBO. There is option to include simultaneous GCase delivery after safety profile review by Data and Safety Monitoring Board (DSMB).	Device: Blood Brain Barrier Disruption - Functional; Delivery of GCase across the BBB to form a disease modifying strategy for patients with Parkinson's Disease
Experimental: GBA PD Patients; GBA PD patients receiving 3 cycles of BBBO. There is option to include simultaneous GCase delivery after safety profile review by Data and Safety Monitoring Board (DSMB).	Device: Blood Brain Barrier Disruption - Functional; Delivery of GCase across the BBB to form a disease modifying strategy for patients with Parkinson's Disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Measure of the adverse events through the intervention phase and follow-up. All adverse events and/or Serious Adverse Events will be documented and reported according to CTCAE criteria.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of MRgFUS BBB opening for GCase brain delivery	Using MRI images to measure: The qualitative measure of the MRI T1-weighted with gadolinium of contract extravasation in the sonicate putamen.; The qualitative measure of the dynamic contrast enhanced (DCE) MRI	12 Months

Collaborators and Investigators

• Sponsor: InSightec

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: September 7, 2022
• First Submitted That Met QC Criteria: September 29, 2022
• First Posted (Actual): October 4, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Parkinson's disease; Glucocerebrosidase; GCase
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: PD016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No