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

NCT ID: NCT05469009

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-14
• Study Completion Date: 2029-07-31

Brief Summary

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).

Detailed 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.

Conditions

Mild Cognitive Impairment; Alzheimer Disease 1

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DEVICE_FEASIBILITY
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Aducanumab

Intervention Type: DRUG

Standard aducanumab therapy will be given by intravenous infusion every 4 weeks for 6 cycles with blood brain barrier opening

Exablate Model 4000 Type 2

Intervention Type: DEVICE

The Exablate Model 4000 will be utilized for the BBBO (blood-brain barrier opening) after each cycle of Aducanumab or Lecanemab administered per label.

Lecanemab

Intervention Type: DRUG

Standard lecanemab therapy will be given by intravenous infusion every 2 weeks for up to 6 cycles with blood brain barrier opening

Interventions

Aducanumab

Standard aducanumab therapy will be given by intravenous infusion every 4 weeks for 6 cycles with blood brain barrier opening

Intervention Type: DRUG

Exablate Model 4000 Type 2

The Exablate Model 4000 will be utilized for the BBBO (blood-brain barrier opening) after each cycle of Aducanumab or Lecanemab administered per label.

Intervention Type: DEVICE

Lecanemab

Standard lecanemab therapy will be given by intravenous infusion every 2 weeks for up to 6 cycles with blood brain barrier opening

Intervention Type: DRUG

Other Intervention Names

Aduhelm; Focused Ultrasound; Leqembi

Eligibility 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
• 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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

InSightec

INDUSTRY

Sponsor Role: collaborator

Ali Rezai

OTHER

Sponsor Role: lead

Responsible Party

Ali Rezai

Neurosurgeon

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ali Rezai, MD, FAANS

Role: PRINCIPAL_INVESTIGATOR

WVU Rockerfeller Neuroscience Institute

Locations

West Virginia University Rockefeller Neuroscience Institute

Morgantown, West Virginia, United States

Countries

United States

Other Identifiers

2110449196

Identifier Type: -

Identifier Source: org_study_id