Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer's Disease Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy

Ali Rezai

Status and phase

Enrolling

Early Phase 1

Conditions

Mild Cognitive Impairment

Alzheimer Disease 1

Treatments

Drug: Lecanemab

Drug: Aducanumab

Device: Exablate Model 4000 Type 2

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT05469009

2110449196

Details and patient eligibility

About

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).

Full description

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.

Enrollment

15 estimated patients

Sex

All

Ages

50 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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)

Exclusion criteria

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.