NCT03321487已完成不适用
Safety and Feasibility of Primary Motor Cortex Blood-Brain Barrier Opening Using Transcranial MR-Guided Focused Ultrasound With Intravenous Ultrasound Contrast Agent in Patients With Amyotrophic Lateral Sclerosis
适应症
干预措施
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
- Safety - Device and Procedure related adverse events
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and feasibility of Blood-Brain Barrier (BBB) opening using transcranial MRI-guided focused ultrasound in conjunction with an intravenous ultrasound contrast agent in patients with Amyotrophic Lateral Sclerosis (ALS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with laboratory supported probable, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria (Brooks et al. 2000).
- •Right-hand dominant male or female aged 18 years or older.
- •Capable of providing informed consent and complying with study procedures, including tolerability in the supine position and MRI examination without significant claustrophobia.
- •If taking riluzole, on a stable dose for at least 30 days prior to Screening Visit.
- •Slow Vital Capacity equal to or more than 50% predicted value for gender, height and age in the 30 days prior to the Screening Visit and able to lie supine without BiPAP.
- •Severe left arm weakness and functional impairment, defined as Medical Research Council muscle strength score equals 3 or less in the index finger abduction and thumb abduction on the left side; OR severe left leg weakness and functional impairment, defined as Medical Research Council muscle strength score equals 3 or less at the hip flexors and ankle dorsiflexors on the left side.
- •Able to communicate during the ExAblate® MRI-guided FUS procedure.
排除标准
- •Unable to complete high-density CT and MRI studies of the head at the Screening Visit or any other MRI contraindication, such as:
- •Large body habitus and not fitting comfortably into the scanner
- •Difficulty lying supine and still for up to 3 hours in the MRI unit or significant claustrophobia
- •MRI findings:
- •Active infection/inflammation
- •Acute or chronic brain hemorrhages, specifically lobar or subcortical microbleeds, siderosis or macrohemorrhages
- •Tumor/space occupying lesion
- •Meningeal enhancement
- •More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp.
- •Clips or other metallic implanted objects in the skull or the brain, except shunts.
- •Significant cardiac disease or unstable hemodynamic status including:
- •Documented myocardial infarction within six months of enrollment
- •Unstable angina on medication
- •Unstable or worsening congestive heart failure
- •Left ventricular ejection fraction below the lower limit of normal
- •History of a hemodynamically unstable cardiac arrhythmia
- •Cardiac or phrenic pacemaker
- •Known right-to-left, bidirectional, or transient right-to-left cardiac shunt
- •Patients with relative contraindications to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation,
- •QT prolongation observed on screening ECG (QTc > 450 for men and >470 for women)
- •Uncontrolled hypertension (systolic > 150 or diastolic BP > 100 on medication).
- •On medications that increase the bleeding risk, specifically: a) aspirin or another antiplatelet medication (clopidogrel, prasugrel, ticlopidine, abciximab) for the last 7 days prior to treatment; b) oral, subcutaneous or intravenous anticoagulant medications, such as oral vitamin K inhibitors for the last 7 days, non-vitamin K inhibitor oral anticoagulant (dabigatran, apixaban, rivaroxaban) for the last 72 hours, and intravenous or subcutaneous heparin-derived compounds for the last 48 hours.
- •History of a bleeding disorder, coagulopathy or a history of spontaneous hemorrhage.
- •Known frontotemporal dementia.
- •Abnormal coagulation profile, specifically: platelet <100,000/μl, Prothrombin Time >14 seconds, activated partial thromboplastin time (aPTT) >36 seconds, and INR > 1.
- •Known cerebral or systemic vasculopathy, specifically cerebral amyloid angiopathy or systemic or central nervous system vasculitis.
- •Known auto-immune condition with or without neurological manifestations (e.g., multiple sclerosis (MS), systemic lupus erythematous (SLE), Rheumatoid arthritis).
- •Current or planned use of oral, intramuscular or intravenous steroid drugs (such as prednisone, prednisolone, dexamethasone, triamcinolone, methylprednisolone, oxandrolone, and others) or immunosuppressant drugs (azathioprine, mycophenolate, tacrolimus, sirolimus, cyclophosphamide, and others) for more than 7 days.
- •Known sensitivity/allergy to gadolinium (an alternative product may be used), DEFINITY® contrast or any of its components.
- •Untreated, uncontrolled sleep apnea.
- •Impaired renal function with cystatin C-based estimated glomerular filtration rate <30 mL/min/1.73m2 and acute renal injury.
- •Currently in a clinical trial involving an investigational product or non-approved use of a drug or device.
- •Known respiratory diseases, specifically: chronic pulmonary disorders e.g., severe/uncontrolled COPD, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, asthma or hay fever.
- •Patients with a history of drug allergies or multiple allergies where the benefit/risk of administering DEFINITY® is considered unfavorable by the study physicians in relation to the product monograph for DEFINITY®.
- •Unqualified fit for the anesthesia by an anesthesiologist assessment, ASA I-III.
研究组 & 干预措施
Stage I Cohort
Experimental
Blood-Brain Barrier opening with MRgFUS. BBB opening of a small volume of the primary motor cortex
干预措施: Blood-Brain Barrier opening with MRgFUS (Device)
Stage II Cohort
Experimental
Blood-Brain Barrier opening with MRgFUS. BBB opening of a larger volume of the primary motor cortex
干预措施: Blood-Brain Barrier opening with MRgFUS (Device)
结局指标
主要结局
Safety - Device and Procedure related adverse events
时间窗: At the time of the ExAblate MRgFUS procedure
The number and severity of device and BBB opening procedure related adverse events will be evaluated.
次要结局
- Degree of contrast enhancement seen on post-procedure MRI(At the time of the ExAblate MRgFUS procedure and 24 hours post-procedure)
研究者
研究点 (1)
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