Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer's Disease Undergoing Aduhelm Therapy.

• Status: Recruiting
• Trial end date: 2029-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to assess the safety and feasibility of administering standard of care monthly Aduhelm (Aducanumab) 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).

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ali Rezai
• Collaborator: InSightec

Criteria

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

• IAmyloid 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 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.