MR-guided Focused Ultrasound Plus GCase

Parkinsons Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05565443
• Other study ID #: PD016
• Status: Recruiting
• Phase: N/A
• Start date: November 30, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2022
• Source: InSightec
• Contact: Nadir Alikacem
• Phone: +12146302000
• Email: nadira[@]insightec.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 14
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

Inclusion Criteria:

• Men or women between age 35 and 75 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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinsons Disease

Intervention

Device:
• Blood Brain Barrier Disruption - Functional
Delivery of GCase across the BBB to form a disease modifying strategy for patients with Parkinson's Disease

Locations

Country	Name	City	State
Canada	Sunybrook Research Institute	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
InSightec

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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