Blood-Brain-Barrier Disruption With Cerezyme in Patient's With Parkinson's Disease
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|ClinicalTrials.gov Identifier: NCT04370665|
Recruitment Status : Active, not recruiting
First Posted : May 1, 2020
Last Update Posted : August 2, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Parkinson Disease||Device: Exablate BBBD with Cerezyme||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||4 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a prospective, single-center, single-arm, open-labelled study to enroll six (6) patients with Parkinson's disease for three biweekly deliveries of Cerezyme® to the unilateral putamen corresponding to the most affected side using Exablate and Definity®-induced BBB opening. This is a dose escalation study. Each subject will be followed for three months after the final procedure.|
|Masking:||None (Open Label)|
|Primary Purpose:||Device Feasibility|
|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|
|Actual Study Start Date :||July 16, 2020|
|Actual Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 2022|
Experimental: Open label single arm
Using Exablate Model 4000 Type-2 to temporarily disrupt the blood brain barrier to deliver Cerezyme in patients with Parkinson's Disease.
Device: Exablate BBBD with Cerezyme
Blood Brain Barrier Disruption via Exablate to deliver Cerezyme.
- Contrast enhancement on MR imaging [ Time Frame: Immediately after MRgFUS BBBD procedure ]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.
- Safety --Adverse events [ Time Frame: Through study completion, an average of 3 months ]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.
- Exploratory effectiveness of Cerezyme delivery via MRgFUS BBB Opening [ Time Frame: 1 day after the final BBBD procedure ]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.
- Exploratory effectiveness of Cerezyme treatment via MRgFUS BBB Opening [ Time Frame: 3 months after the final BBBD procedure. ]Exploratory effectiveness of Cerezyme treatment via MRgFUS BBB Opening will be measured by changes in cognitive impairment via Mini-Mental Status Exam (MMSE).
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|Ages Eligible for Study:||35 Years to 75 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Men or women between age 35 and 75 years, inclusive.
- Able and willing to give informed consent.
- Diagnosis of Parkinson's Disease.
- At least 2 years from initial diagnosis
- On stable regiment of PD medications for at least 90 days prior to the study
- Able to communicate during the Exablate MRgFUS procedure.
- Able to attend all study visits.
- Previous neurosurgical procedure for PD
- Cerezyme hypersensitivity
- Patients who had recent intracranial hemorrhage or stroke
- 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.
- 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).
- Patients with a history of a bleeding disorder, blood clotting, coagulopathy or with a history of spontaneous tumor hemorrhage.
- Patients receiving bevacizumab (Avastin) therapy.
- Currently participating in another clinical therapeutic trial
- Documented myocardial infarction within six months of enrollment.
- Unstable angina on medication.
- Congestive heart failure.
- Unstable cardiac arrhythmia.
- Cardiac pacemaker.
- Severe hypertension (diastolic BP > 100 on medication).
- Documented cerebral infarction within the past 12 months or TIA in the past 1 month.
- Insulin-dependent diabetes mellitus that is not well-controlled or that in the Investigator's opinion precludes participation in the study.
- Known sensitivity to gadolinium
- Known sensitivity to DEFINITY ultrasound contrast agent or perflutren.
- Contraindications to MRI such as non-MRI-compatible implanted devices.
- Large subjects not fitting comfortably into the MRI scanner.
- Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia.
- Untreated, uncontrolled sleep apnea.
- Positive pregnancy test (for pre-menopausal women).
- Known life-threatening systemic disease.
- Severely impaired renal function and/or on dialysis.
- Right to left or bi-directional cardiac shunt.
- Subjects with evidence of cranial or systemic infection.
- Subjects with uncontrolled chronic pulmonary disorders.
- Subjects with a history of severe asthma, hay fever, or multiple allergies that is not well-controlled (e.g. with anaphylaxis).
- Subjects with a family or personal history of cardiac arrhythmia.
- Severe liver injury.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04370665
|Sunnybrook Health Sciences Centre|
|Toronto, Ontario, Canada, M4N 3M5|
|Other Study ID Numbers:||
|First Posted:||May 1, 2020 Key Record Dates|
|Last Update Posted:||August 2, 2022|
|Last Verified:||August 2022|
|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|
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