Neuronavigation-guided Focused Ultrasound-induced Blood-brain Barrier Opening in Alzheimer's Disease Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Total Number of Safety Events Related to Opening of BBB
研究概览
简要总结
The purpose of this study is to test a new technique that may, in the future, help deliver medications to the brain of people with Alzheimer's disease. Participants in this study will undergo a focused ultrasound treatment to the brain, along with Magnetic Resonance Imagine (MRI) and Positron Emission Tomography (PET) scans.
详细描述
Central nervous system disorders are currently being symptomatically treated since the molecular events provoking their onset have not been yet identified. Drug delivery techniques have to overcome the almost impermeable blood-brain barrier (BBB) and can be grouped into two main categories: (i) invasive and targeted, and (ii) non-invasive and non-targeted methods. However, the technological advances of the past decades revealed the immense potential of focused ultrasound (FUS) in transcranial applications. In contrast to other techniques, FUS-mediated BBB opening is both non-invasive and targeted. The localized energy delivery coupled with the circulation of intravenously administered microbubbles initiates biological effects confined only to the vessel walls and contained only in the targeted region within the brain.
The purpose of the study is to assess the safety and feasibility of focused ultrasound-induced blood-brain barrier opening in Alzheimer's disease patients, using a single-element transducer with neuronavigation guidance. The investigators will also test whether treatment with focused ultrasound alone alters the amyloid protein levels in the treated brain areas and its potential effects on the cognitive function of Alzheimer's patients.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •50 years of age or older.
- •Diagnosis of early Alzheimer's disease (AD) or mild cognitive impairment (MCI) at minimum. All following criteria must be met:
- •Probable MCI or AD consistent with criteria outlined in (McKhann et al 2011, Petersen et al 2018).
- •Mini Mental State Examination (MMSE) score between 12 and
- •Modified Hachinski Ischemia Scale (MHIS) score of <= 4
- •Short form Geriatric Depression Scale (GDS) score of <=
- •PET scan confirming amyloid plaque load using Amyvid (18F-Florbetapir).
- •Ability to provide informed consent.
排除标准
- •Contraindication for Magnetic Resonance Imaging (MRI).
- •Contra-indication history or hypersensitivity to MRI contrast agents (e.g., Dotarem) or microbubbles (e.g., Definity).
- •Prior brain surgery, including deep brain stimulation.
- •Metallic implants.
- •Moderate or severe uncontrolled hypertension (systolic blood pressure > 140 mmHg).
- •Abnormal coagulation profile, e.g. hemophilia A or B.
- •Coagulopathy or under anticoagulant therapy.
- •History of stroke or cardiovascular disease.
- •Active/detectable gingivitis, herpes simplex, hepatitis, tuberculosis, and minor skin or respiratory infections.
- •History of seizure disorder.
- •History of asthma or allergies to food or medication with significant symptoms in past 3 years.
- •Severe brain atrophy.
- •Inability to comply with the procedures of the protocol, including follow-up MRI scans.
- •Pregnancy or lactation.
- •Impaired renal function with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 provided by a standard blood test at maximum 2 weeks prior to the ultrasound treatment.
- •Active infection/inflammation.
- •Acute or chronic hemorrhages, i.e. > 4 lobar microbleeds, and no siderosis or macrohemorrhages.
- •Tumors or space occupying lesions.
- •Meningeal enhancements.
- •Intracranial hypotension.
研究组 & 干预措施
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg).
干预措施: Neuronavigation-guided single-element focused ultrasound transducer (Device)
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg).
干预措施: Definity (Drug)
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg).
干预措施: Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents (Other)
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg).
干预措施: Positron Emission Tomography (PET) (Other)
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg).
干预措施: Amyvid (Other)
结局指标
主要结局
Total Number of Safety Events Related to Opening of BBB
时间窗: Baseline through 3 days post-treatment
The total number of safety events related to opening of the BBB as assessed by T2 and susceptibility-weighted (SWI) MRI. Safety will be established by the presence and the total area of hyper-intense or hypo-intense areas in the T2 and SWI scans.
Total Number of Individuals With Successful Opening of the BBB
时间窗: Baseline through 3 days post-treatment
The total number of individuals with successful opening of the BBB will be assessed. Blood-brain barrier opening volume will be measured in mm\^3 through contrast-enhanced T1-weighted MRI on the day of the focused ultrasound treatment and 3 days after treatment, to confirm blood-brain barrier restoration.
次要结局
- Change in Mini-Mental State Examination (MMSE) Score(Screening through 3 months post-treatment)
- Percent Change in Amyloid PET Signal Intensity(Screening through 3 weeks post-treatment)