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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- InSightec
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Contrast enhancement on MR imaging
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Device Feasibility
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Exablate BBBD with Cerezyme (Device)
结局指标
主要结局
Contrast enhancement on MR imaging
时间窗: 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.
次要结局
- Safety --Adverse events(Through study completion, an average of 3 months)