Blood-Brain-Barrier Disruption With Cerezyme in Patient's With Parkinson's Disease

Parkinson Disease Clinical Trial

Official title:

A Pilot Study for Brain Delivery of Cerezyme® in Patients With Parkinson's Disease Using MR-guided Focused Ultrasound Induced Opening of the Blood-brain Barrier

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04370665
• Other study ID #: PD013
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 16, 2020
• Est. completion date: December 2022

Study information

• Verified date: August 2022
• Source: InSightec
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial focus on the delivery of Cerezyme® in Parkinson's Disease (PD) patients using MR-guided focused ultrasound (MRgFUS) induced opening of the blood-brain barrier (BBB).

Description:

Leveraging the preclinical evidence and clinical experience with MRgFUS BBB opening in human subjects, the investigators propose a phase I open-label study to determine the safety and feasibility of three biweekly delivery of Cerezyme® (an analogue of the human enzyme beta-glucocerebrosidase) via MRgFUS induced BBB opening to unilateral putamen in PD. The putamen contains terminals of dopaminergic neurons from the substantia nigra, and is a critically affected brain region in PD. The primary objective is to determine the feasibility of repeated MRgFUS BBB opening for Cerezyme delivery in unilateral putamen. The secondary objective is to describe the safety and tolerability of the procedure. Another objective is to measure changes in PD relevant clinical scores and Cerezyme relevant biomarkers in the study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4
• Est. completion date: December 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Men or women between age 35 and 75 years, inclusive.

2. Able and willing to give informed consent.

3. Diagnosis of Parkinson's Disease.

4. At least 2 years from initial diagnosis

5. On stable regiment of PD medications for at least 90 days prior to the study

6. Able to communicate during the Exablate MRgFUS procedure.

7. Able to attend all study visits.

Exclusion Criteria:

1. Previous neurosurgical procedure for PD

2. Cerezyme hypersensitivity

3. Patients who had recent intracranial hemorrhage or stroke

4. Skull covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp. Patients who have clips or other metallic implanted objects in the skull or the brain.

5. Patients who are on blood thinners within washout period prior to treatment (i.e., antiplatelet or vitamin K inhibitor anticoagulants within 7 days, non-vitamin K inhibitor anticoagulants within 72 hours, or heparin-derived compounds within 48 hours of treatment).

6. Patients with a history of a bleeding disorder, blood clotting, coagulopathy or with a history of spontaneous tumor hemorrhage.

7. Patients receiving bevacizumab (Avastin) therapy.

8. Currently participating in another clinical therapeutic trial

9. Documented myocardial infarction within six months of enrollment.

10. Unstable angina on medication.

11. Congestive heart failure.

12. Unstable cardiac arrhythmia.

13. Cardiac pacemaker.

14. Severe hypertension (diastolic BP > 100 on medication).

15. Documented cerebral infarction within the past 12 months or TIA in the past 1 month.

16. Insulin-dependent diabetes mellitus that is not well-controlled or that in the Investigator's opinion precludes participation in the study.

17. Known sensitivity to gadolinium

18. Known sensitivity to DEFINITY ultrasound contrast agent or perflutren.

19. Contraindications to MRI such as non-MRI-compatible implanted devices.

20. Large subjects not fitting comfortably into the MRI scanner.

21. Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia.

22. Untreated, uncontrolled sleep apnea.

23. Positive pregnancy test (for pre-menopausal women).

24. Known life-threatening systemic disease.

25. Severely impaired renal function and/or on dialysis.

26. Right to left or bi-directional cardiac shunt.

27. Subjects with evidence of cranial or systemic infection.

28. Subjects with uncontrolled chronic pulmonary disorders.

29. Subjects with a history of severe asthma, hay fever, or multiple allergies that is not well-controlled (e.g. with anaphylaxis).

30. Subjects with a family or personal history of cardiac arrhythmia.

31. Severe liver injury.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Device:
• Exablate BBBD with Cerezyme
Blood Brain Barrier Disruption via Exablate to deliver Cerezyme. Other Names: Exablate Neuro

Locations

Country	Name	City	State
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
InSightec

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory effectiveness of Cerezyme delivery via MRgFUS BBB Opening	Exploratory effectiveness of Cerezyme delivery via MRgFUS BBB Opening will be measured by changes in levels of Cerezyme (GCase) and GCase substrates levels (e.g. GL1 and glucosylsphingosine or lyso-GL1) in cerebralspinal fluid (CSF) samples.	1 day after the final BBBD procedure
Other	Exploratory effectiveness of Cerezyme treatment via MRgFUS BBB Opening	Exploratory effectiveness of Cerezyme treatment via MRgFUS BBB Opening will be measured by changes in cognitive impairment via Mini-Mental Status Exam (MMSE).	3 months after the final BBBD procedure.
Primary	Contrast enhancement on MR imaging	MRgFUS BBB Opening will be determined qualitatively by contrast enhancement in the sonicated putamen on T1-weighted with gadolinium MRI, and quantitatively by the change in intensity relative to contralateral unsonicated putamen immediately after MRgFUS BBBD procedure.	Immediately after MRgFUS BBBD procedure
Secondary	Safety --Adverse events	Safety will be assessed by recording all adverse events and/or Serious Adverse Events that are BBBD related. Each Adverse Event will be documented for patterns of occurrence.	Through study completion, an average of 3 months