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

Study Overview
=================
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).

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.

Official Title
-----------------
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

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Device: Blood Brain Barrier (BBB) Disruption


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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 Positive human immunodeficiency virus (HIV) Known apolipoprotein E allele (ApoE4) homozygosity

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Magnetic Resonance guided Focal Ultrasound (MRgFUS), Alzheimer's Disease, ExAblate, Blood Brain Barrier