RecruitingNot ApplicableNCT05565443

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


Sponsor

InSightec

Enrollment

14 participants

Start Date

Nov 30, 2022

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 35 YearsMax Age: 80 Years

Inclusion Criteria9

  • 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 Criteria13

  • 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

Interventions

DEVICEBlood Brain Barrier Disruption - Functional

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


Locations(1)

Sunybrook Research Institute

Toronto, Ontario, Canada

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NCT05565443


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