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MR-guided Focused Ultrasound Plus GCase

Primary Purpose

Parkinsons Disease

Status

Recruiting

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Blood Brain Barrier Disruption - Functional

About this trial

This is an interventional treatment trial for Parkinsons Disease focused on measuring Parkinson's disease, Glucocerebrosidase, GCase

Eligibility Criteria

35 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Sunybrook Research InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Idiopathic PD Patients

GBA PD Patients

Arm Description

Idiopathic PD patients receiving 3 cycles of BBBO paired with GCase Treatments

GBA PD patients receiving 3 cycles of BBBO paired with GCase Treatments

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

NCT ID

NCT05565443

First Posted

September 7, 2022

Last Updated

September 1, 2023

Sponsor

InSightec

1. Study Identification

Unique Protocol Identification Number

NCT05565443

Brief Title

MR-guided Focused Ultrasound Plus GCase

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 30, 2022 (Actual)

Primary Completion Date

December 31, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

InSightec

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinsons Disease

Keywords

Parkinson's disease, Glucocerebrosidase, GCase

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

A two-arm, open-label, intervention only clinical study. One arm to enroll 7 GBA PD patients, the second arm to enroll 7 idiopathic PD patients. In each arm, the first four subjects will take part in 3 focused ultrasound procedures along with 30 IU/Kg infusion of GCase. The next three subjects will take part in 3 focused ultrasound procedures along with 60 IU/Kg infusion of GCase.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Idiopathic PD Patients

Arm Type

Experimental

Arm Description

Idiopathic PD patients receiving 3 cycles of BBBO paired with GCase Treatments

Arm Title

GBA PD Patients

Arm Type

Experimental

Arm Description

GBA PD patients receiving 3 cycles of BBBO paired with GCase Treatments

Intervention Type

Device

Intervention Name(s)

Blood Brain Barrier Disruption - Functional

Intervention Description

Delivery of GCase across the BBB to form a disease modifying strategy for patients with Parkinson's Disease

Primary Outcome Measure Information:

Title

Adverse Events

Description

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.

Time Frame

12 Months

Secondary Outcome Measure Information:

Title

Feasibility of MRgFUS BBB opening for GCase brain delivery

Description

Time Frame

12 Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

35 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Nadir Alikacem

Phone

+12146302000

nadira@insightec.com

Facility Information:

Facility Name

Sunybrook Research Institute

City

Toronto

State/Province

Ontario

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Allison Bethune

Allison.Bethune@sunnybrook.ca

12. IPD Sharing Statement

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MR-guided Focused Ultrasound Plus GCase

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