ExAblate Blood-Brain Barrier Opening for Treatment of Alzheimer's Disease

A Phase IIa Study to Evaluate the Safety and Efficacy of Blood-Brain Barrier (BBB) Opening Using Transcranial MR-Guided Focused Ultrasound in Patients With Alzheimer's Disease

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).

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Device: Blood Brain Barrier (BBB) Disruption

Detailed Description

This study is a prospective, open label, single-arm, non-randomized, phase IIa trial to evaluate the feasibility, safety and efficacy of repeated, BBB opening using the ExAblate® Model Type 2.0 (220 kHz) system. Patients with diagnosis of Probable Alzheimer's Disease may qualify for a clinical trial to have three serial ExAblate BBB disruption procedures in specific areas in the brain.This study will be conducted at a single center in Canada and will enroll up to 30 patients.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Division of Neurosurgery, Sunnybrook Health Sciences Centre
      • Contact: Allison Bethune; Phone Number: 4831 416-480-6100; Email: allison.bethune@sunnybrook.ca
      • Principal Investigator: Nir Lipsman, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or Female between 50-85 years of age
2. Probable Alzheimer's Disease (AD)
3. 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
4. Able to communicate sensations during the ExAblate MRgFUS procedure
5. Ambulatory

Exclusion Criteria:

1. MRI Findings
2. Presence of unknown or MR unsafe devices anywhere in the body
3. Significant cardiac disease or unstable hemodynamic status
4. Relative contraindications to ultrasound contrast agent or PET amyloid tracer
5. History of a bleeding disorder
6. History of liver disease
7. Known cerebral or systemic vasculopathy
8. Significant depression and at potential risk of suicide
9. Any contraindications to MRI scanning
10. Any contraindication to lumbar puncture for collection of cerebral spinal fluid
11. Untreated, uncontrolled sleep apnea
12. History of seizure disorder or epilepsy
13. Severely Impaired renal function
14. 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
15. Chronic pulmonary disorders
16. Positive human immunodeficiency virus (HIV)
17. Known apolipoprotein E allele (ApoE4) homozygosity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blood Brain Barrier (BBB) Disruption; The ExAblate Model 4000 Type 2.0 System	Device: Blood Brain Barrier (BBB) Disruption; Focal Ultrasound (FUS) involves the application of acoustic energy at low frequencies from over 1000 individual transducers into distinct targets to induce BBB disruption.; Other Names: ExAblate Neuro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device and procedure related adverse events	Rate of adverse events following each treatment through end of study	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BBB Disruption and Closure	MRI images post ExAblate treatment to verify that the BBB was disrupted and subsequently closed	Immediately after the end of each ExAblate treatment and 24 hours after each treatment
Change in Alzheimer's Disease Assessment Scale-Cognition	Mental cognition assessment	Baseline and 6 months
Change in Amyloid Tracer uptake	PET scan analysis comparing the Amyloid Tracer uptake on images taken at baseline and after the last treatment	Baseline and Day 8 following the third treatment

Collaborators and Investigators

• Sponsor: InSightec
• Collaborators: Focused Ultrasound Foundation

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2018
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: November 2, 2018
• First Submitted That Met QC Criteria: November 9, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; ExAblate; Blood Brain Barrier; Magnetic Resonance guided Focal Ultrasound (MRgFUS)
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: AL003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No