Assessment of Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for the Treatment of Patients With With Mild Cognitive Impairment (MCI) or Mild Alzheimer's Disease (AD) Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy
试验速览
- 阶段
- 早期 1 期
- 状态
- 进行中（未招募）
- 发起方
- Ali Rezai
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Treatment intervention related adverse events
研究概览
简要总结
The purpose of this study is to assess the safety and feasibility of administering standard of care monoclonal antibody (mAb) infusion therapy in combination with opening the blood-brain barrier with the Exablate Model 4000 Type 2 device in patients with mild Alzheimer's disease (AD) or mild cognitive impairment (MCI).
详细描述
The primary objectives of this study is to evaluate the safety and feasibility of BBBO (blood-brain barrier opening) using the Exablate Model 4000 Type 2 in the setting of standard aducanumab or lecanemab therapy among patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD) with confirmed β-amyloid, who are eligible for aducanumab or lecanemab infusion therapy, and to also evaluate the safety of the BBO procedure through patient examination (neurological and cognitive/behavioral) and MRI assessments during the treatment and follow-up.
The secondary objectives of this study is to determine the effect of BBBO in patients with MCI or mild AD treated with aducanumab or lecanemab on brain β-amyloid plaque measured by amyloid positron emission tomography (PET), as well as to assess the clinical impact of BBBO with standard aducanumab or lecanemab therapy, if any, as assessed with ADAS Cog 11 and MMSE over time following BBBO.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to give informed consent
- •Probable mild cognitive impairment due to AD
- •Modified Hachinski Ischemia Scale (MHIS) score of <= 4
- •Mini Mental State Exam (MMSE) scores > 21+.
- •Short form Geriatric Depression Scale (GDS) score of <= 7
- •Amyloid PET scan consistent with the presence of β-amyloid (A+)
- •Able to communicate sensations during the Exablate MRgFUS procedure
- •Able to attend all study visits (i.e., life expectancy of 1 year or more)
排除标准
- •MRI findings:
- •Significant cardiac disease or unstable hemodynamic status
- •History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage
- •Known cerebral or systemic vasculopathy
- •Significant depression (GDS > 7) and/or at potential risk of suicide (C-SSRS > 2)
- •A severity score of 2 or more on any of the 'Delusions', 'Hallucinations' or 'Agitation/Aggression' subscales of the Neuropsychiatry Inventory (NPI-Q)
- •Known sensitivity/allergy to gadolinium(gadobutrol), DEFINITY or its components, or 18F-florbetaben.
- •Known hypersensitivity to DEFINITY or its components.
- •Any contraindications to MRI scanning
- •Untreated, uncontrolled sleep apnea
- •History of untreated or uncontrolled seizure disorder or epilepsy.
- •Impaired renal function
- •Does not have a reliable caregiver
- •Currently in a clinical trial involving an investigational product or non-approved use of a drug or device or in any other type of medical research.
- •Respiratory: chronic pulmonary disorders
- •History of clinically significant recent drug or alcohol use disorder who may be at higher risk for seizure or infection.
- •Positive human immunodeficiency virus (HIV) which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis.
- •Potential blood-borne infections, which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess.
研究组 & 干预措施
Infusion plus Exablate BBBO Treatment
Intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS.
干预措施: Aducanumab (Drug)
Infusion plus Exablate BBBO Treatment
Intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS.
干预措施: Exablate Model 4000 Type 2 (Device)
Infusion plus Exablate BBBO Treatment
Intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS.
干预措施: Lecanemab (Drug)
结局指标
主要结局
Treatment intervention related adverse events
时间窗: From baseline, up to 5 year post last treatment
The total number of adverse events following each treatment through end of the study
Treatment intervention related serious adverse events
时间窗: From baseline, up to 5 year post last treatment
The total number of serious adverse events following each treatment through end of the study
次要结局
- Cognitive performance (MMSE)(From baseline, up to 5 year post last treatment)
- Cognitive performance (ADAS COG 11)(From baseline, up to 5 year post last treatment)
- Beta-Amyloid plaques within the brain(From baseline, up to 5 year post last treatment)