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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- InSightec
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Adverse Events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 80 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 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
排除标准
- •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
研究组 & 干预措施
Idiopathic PD Patients
Idiopathic PD patients receiving 3 cycles of BBBO. There is option to include simultaneous GCase delivery after safety profile review by Data and Safety Monitoring Board (DSMB).
干预措施: Blood Brain Barrier Disruption - Functional (Device)
GBA PD Patients
GBA PD patients receiving 3 cycles of BBBO. There is option to include simultaneous GCase delivery after safety profile review by Data and Safety Monitoring Board (DSMB).
干预措施: Blood Brain Barrier Disruption - Functional (Device)
结局指标
主要结局
Adverse Events
时间窗: 12 Months
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.
次要结局
- Feasibility of MRgFUS BBB opening for GCase brain delivery(12 Months)