NCT03739905

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of the ExAblate® Model 4000 Type 2.0 system as a tool to open the blood-brain barrier (BBB) in patients with probable Alzheimer's Disease (AD).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P25-P50 for not_applicable alzheimer-disease

Timeline
Completed

Started Dec 2018

Longer than P75 for not_applicable alzheimer-disease

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 2, 2018

Completed
12 days until next milestone

First Posted

Study publicly available on registry

November 14, 2018

Completed
22 days until next milestone

Study Start

First participant enrolled

December 6, 2018

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 9, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 9, 2025

Completed
Last Updated

January 21, 2026

Status Verified

January 1, 2026

Enrollment Period

6.3 years

First QC Date

November 2, 2018

Last Update Submit

January 16, 2026

Conditions

Alzheimer Disease

Keywords

Magnetic Resonance guided Focal Ultrasound (MRgFUS)Alzheimer's DiseaseExAblateBlood Brain Barrier

Outcome Measures

Primary Outcomes (1)

  • Device and procedure related adverse events

    Rate of adverse events following each treatment through end of study

    6 months

Secondary Outcomes (3)

  • BBB Disruption and Closure

    Immediately after the end of each ExAblate treatment and 24 hours after each treatment

  • Change in Alzheimer's Disease Assessment Scale-Cognition

    Baseline and 6 months

  • Change in Amyloid Tracer uptake

    Baseline and Day 8 following the third treatment

Study Arms (1)

Blood Brain Barrier (BBB) Disruption

EXPERIMENTAL

The ExAblate Model 4000 Type 2.0 System

Device: Blood Brain Barrier (BBB) Disruption

Interventions

Blood Brain Barrier (BBB) DisruptionDEVICE

Focal Ultrasound (FUS) involves the application of acoustic energy at low frequencies from over 1000 individual transducers into distinct targets to induce BBB disruption.

Also known as: ExAblate Neuro
Blood Brain Barrier (BBB) Disruption

Eligibility Criteria

Age50 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or Female between 50-85 years of age
  • Probable Alzheimer's Disease (AD)
  • If taking concurrent Alzheimer's medication, has been on the medication for at least 2 months with a stable dose for at least 3 months
  • Able to communicate sensations during the ExAblate MRgFUS procedure
  • Ambulatory

You may not qualify if:

  • MRI Findings
  • Presence of unknown or MR unsafe devices anywhere in the body
  • Significant cardiac disease or unstable hemodynamic status
  • Relative contraindications to ultrasound contrast agent or PET amyloid tracer
  • History of a bleeding disorder
  • History of liver disease
  • Known cerebral or systemic vasculopathy
  • Significant depression and at potential risk of suicide
  • Any contraindications to MRI scanning
  • Any contraindication to lumbar puncture for collection of cerebral spinal fluid
  • Untreated, uncontrolled sleep apnea
  • History of seizure disorder or epilepsy
  • Severely Impaired renal function
  • 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
  • Chronic pulmonary disorders
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Division of Neurosurgery, Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (3)

  • Meng Y, Goubran M, Rabin JS, McSweeney M, Ottoy J, Pople CB, Huang Y, Storace A, Ozzoude M, Bethune A, Lam B, Swardfager W, Heyn C, Abrahao A, Davidson B, Hamani C, Aubert I, Zetterberg H, Ashton NJ, Karikari TK, Blennow K, Black SE, Hynynen K, Lipsman N. Blood-brain barrier opening of the default mode network in Alzheimer's disease with magnetic resonance-guided focused ultrasound. Brain. 2023 Mar 1;146(3):865-872. doi: 10.1093/brain/awac459.

    PMID: 36694943DERIVED

  • Mathew AS, Gorick CM, Price RJ. Multiple regression analysis of a comprehensive transcriptomic data assembly elucidates mechanically- and biochemically-driven responses to focused ultrasound blood-brain barrier disruption. Theranostics. 2021 Oct 11;11(20):9847-9858. doi: 10.7150/thno.65064. eCollection 2021.

    PMID: 34815790DERIVED

  • Meng Y, Pople CB, Suppiah S, Llinas M, Huang Y, Sahgal A, Perry J, Keith J, Davidson B, Hamani C, Amemiya Y, Seth A, Leong H, Heyn CC, Aubert I, Hynynen K, Lipsman N. MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors. Neuro Oncol. 2021 Oct 1;23(10):1789-1797. doi: 10.1093/neuonc/noab057.

    PMID: 33693781DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 2, 2018

First Posted

November 14, 2018

Study Start

December 6, 2018

Primary Completion

April 9, 2025

Study Completion

April 9, 2025

Last Updated

January 21, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)