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

NCT05469009 | Active Not Recruiting Early Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 2110449196
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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).

Conditions

Mild Cognitive Impairment; Alzheimer Disease 1

Outcome Measures

Primary Outcomes (2)

• Treatment intervention related adverse events

  The total number of adverse events following each treatment through end of the study

  From baseline, up to 5 year post last treatment

• Treatment intervention related serious adverse events

  The total number of serious adverse events following each treatment through end of the study

  From baseline, up to 5 year post last treatment

Secondary Outcomes (3)

• Beta-Amyloid plaques within the brain

  From baseline, up to 5 year post last treatment

• Cognitive performance (ADAS COG 11)

  From baseline, up to 5 year post last treatment

• Cognitive performance (MMSE)

  From baseline, up to 5 year post last treatment

Study Arms (1)

Infusion plus Exablate BBBO Treatment

EXPERIMENTAL

Intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS.

Drug: Aducanumab; Device: Exablate Model 4000 Type 2; Drug: Lecanemab

Interventions

Aducanumab DRUG

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

Also known as: Aduhelm

Infusion plus Exablate BBBO Treatment

Exablate Model 4000 Type 2 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.

Also known as: Focused Ultrasound

Infusion plus Exablate BBBO Treatment

Lecanemab DRUG

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

Also known as: Leqembi

Infusion plus Exablate BBBO Treatment

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ali Rezai: lead
• InSightec: collaborator

Study Sites (1)

West Virginia University Rockefeller Neuroscience Institute

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer disease type 1

Interventions

aducanumab; lecanemab

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Ali Rezai, MD, FAANS

  WVU Rockerfeller Neuroscience Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Neurosurgeon

Study Record Dates

• First Submitted: July 19, 2022
• First Posted: July 21, 2022
• Study Start: July 14, 2022
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: January 22, 2026

Record last verified: 2025-11

Locations

US (1)