Single-center, Open, Prospective, Single-arm, Feasibility, Investigator-initiated Trail for Assessment of Initial Efficacy and Safety of High Intensity Focused Ultrasound 'ExAblate 4000 Type 2' for Blood Brain Barrier Disruption in Patients With Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Adverse events safety profile
研究概览
简要总结
The proposed study is to evaluate initial efficacy and safety of the BBB disruption with transcranial MRI-guided focused ultrasound (ExAblate 4000 type 2.0) in patients with Alzheimer's disease.
This study iw designed as a prospective, single-site, single-aarm, nonrandomized study. Assessments will be made before and three months after 2 sessions of BBB disruption with radiologic, nuclear medicine imaging and neurophysiological examinations. Relative safety will be evaluated using a common description of Significant Clinical Complications for patients treated in this 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
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 50 and 85 years, inclusive.
- •Total score of 23 or less on the Korean version of Mini Mental state Exam (K-MMSE)
- •FBB (18F-Florbetaben)-PET test result positive
- •FDB (18F-Fluorodeoxyglucose)-PET test results suspected of Alzheimer disease-induced neurodegeneration
- •Mild cognitive impairment or dementia caused by Alzheimer's disease
- •A participant who has been given a drug at a stable dose for at least three months to improve symptoms of Alzheimer's disease
- •Able to communicate during the ExAblate BBB disruption procedure
- •Able and willing to give informed consent
- •Able to attend all study visits
排除标准
- •CGA-NPI (Caregiver-Administrated Neuropsychiatry Inventory) severity score of more than 2 points for any of "Delusion", "Hallucination" or "Agitation/Aggression"
- •Known sensitivity/allergy or contraindications to MRI contrast agent(Gadovist®) or the ultrasound contrast agent (Definity®)
- •Contraindications to MRI such as non-MRI compatible implanted devices.
- •Any of the following items in MRI
- •severe ischemic changes
- •active or chronic infection/inflammation
- •acute or chronic hemorrhage
- •tumor/space occupying lesion
- •meningeal enhancement
- •intracranial hypotension
- •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
- •Active seizure disorder or epilepsy (seizures despite medical treatment)
- •History of a bleeding disorder, coagulopathy
- •Cardiac disease or unstable hemodynamics
- •Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2
- •Severe brain atrophy
- •HIV (Human immunodeficiency virus) positive, who have a high probability of developing HIV encephalitis due to the influx of HIV in to the brain parenchyma
- •Subjects with evidence of cranial or systemic infection
- •A homozygosity of Apolipoprotein E allele (ApoE4) known to have a thin blood-brain barrier
- •Positive pregnancy test (women of childbearing potential)
- •A participant in other clinical trials or have experience in other clinical trials within 90 days from the screening date
结局指标
主要结局
Adverse events safety profile
时间窗: 6 months
The type and severity of post-procedure adverse events will be assessed for overall safety. Safety of the BBBD procedure will be evaluated through patient examination and MRI assessements during the treatment and by their standard care of follow-up MRI scans and clinical visits.
次要结局
- Efficacy of BBB disruption : evaluated by nuclear medicine imaging(6 months)
- Efficacy of BBB disruption : evaluated by neurophysiological examination(6 months)
- Efficacy of BBB disruption : evaluated by radiologic imaging(6 months)