Alzheimer DiseaseNCT03739905
ExAblate Blood-Brain Barrier Opening for Treatment of Alzheimer's Disease
A study testing Blood Brain Barrier (BBB) Disruption in people with Alzheimer Disease, run by InSightec at 1 site in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Blood Brain Barrier (BBB) Disruption
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteCanada
- Study dates
- 6 Dec 2018to 9 Apr 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Division of Neurosurgery, Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
About this study
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
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).
Read the 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.
- Conditions
- Alzheimer Disease
- Being tested
- Blood Brain Barrier (BBB) Disruption
- Keywords
- Magnetic Resonance guided Focal Ultrasound (MRgFUS), Alzheimer's Disease, ExAblate, Blood Brain Barrier
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood Brain Barrier (BBB) DisruptionDevice
Also called ExAblate Neuro
Focal Ultrasound (FUS) involves the application of acoustic energy at low frequencies from over 1000 individual transducers into distinct targets to induce BBB disruption.
| Study group | Role | What they receive |
|---|---|---|
| Blood Brain Barrier (BBB) Disruption | Experimental | The ExAblate Model 4000 Type 2.0 System Receives: Device: Blood Brain Barrier (BBB) Disruption |
What is being measured
The primary outcome is the main question the study is designed to answer.
Device and procedure related adverse events
Rate of adverse events following each treatment through end of study
Measured: 6 months
Secondary outcomes (3)
BBB Disruption and Closure
MRI images post ExAblate treatment to verify that the BBB was disrupted and subsequently closed
Measured: 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
Measured: 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
Measured: Baseline and Day 8 following the third treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2018
- Study start6 Dec 2018
- Primary completion9 Apr 2025
- Study completion9 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by InSightecThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- InSightec
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Focused Ultrasound Foundation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03739905
- Sponsor's protocol ID
- AL003
- Status last verified
- Jan 2026
- First submitted
- 2 Nov 2018
- Last updated
- 21 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36694943Mathew 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.
PubMed 34815790Meng 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.
PubMed 33693781
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03739905
- Acronym / sponsor ID
- AL003
- Conditions
- Alzheimer Disease
- Keywords
- Magnetic Resonance guided Focal Ultrasound (MRgFUS), Alzheimer's Disease, ExAblate, Blood Brain Barrier
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- InSightecIndustry (pharma, biotech, devices)
- Collaborators
- Focused Ultrasound Foundation
- Study start
- 6 Dec 2018 (actual)
- Primary completion
- 9 Apr 2025 (actual)
- Study completion
- 9 Apr 2025 (actual)
- First posted
- 14 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Blood Brain Barrier (BBB) Disruption | Experimental | Device: Blood Brain Barrier (BBB) DisruptionThe ExAblate Model 4000 Type 2.0 System |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood Brain Barrier (BBB) DisruptionAlso: ExAblate NeuroFocal Ultrasound (FUS) involves the application of acoustic energy at low frequencies from over 1000 individual transducers into distinct targets to induce BBB disruption. | Device | Blood Brain Barrier (BBB) Disruption |
Primary outcome
Device and procedure related adverse events
Time frame: 6 months
Rate of adverse events following each treatment through end of study
3 secondary outcomes
BBB Disruption and Closure
Time frame: Immediately after the end of each ExAblate treatment and 24 hours after each treatment
Change in Alzheimer's Disease Assessment Scale-Cognition
Time frame: Baseline and 6 months
Change in Amyloid Tracer uptake
Time frame: Baseline and Day 8 following the third treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2026.
- Derived from this study: PubMed 36694943Meng 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.
- Derived from this study: PubMed 34815790Mathew 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.
- Derived from this study: PubMed 33693781Meng 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood Brain Barrier (BBB) Disruption in people with Alzheimer Disease, run by InSightec at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Device and procedure related adverse events (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03739905, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2026.