Alzheimer DiseaseNCT03671889
ExAblate Blood-Brain Barrier (BBB) Disruption for the Treatment of Alzheimer's Disease
A study testing Blood Brain Barrier (BBB) Disruption in people with Alzheimer Disease, run by InSightec at 10 sites in United States.
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 disrupt 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
- 50 participants
- Where
- 10 sitesUnited States
- Study dates
- 28 Sep 2018to Jan 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
United States10 sites, 6 recruiting
- Active, not recruiting
The Ohio State University -Wexner Medical Center
Columbus, Ohio, 43210
- Active, not recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
- Recruiting
Delray Medical Center & Florida Atlantic University
Delray Beach, Florida, 33484
Jenny Zucker, MS, 561-825-1505, JennyZucker712@gmail.com
Lloyd Zucker, MD, FAANS
- Recruiting
Broward Health Medical Center & The University of Florida
Fort Lauderdale, Florida, 33316
Joan Osborne, EdD, 954-355-5563, BHResearch@browardhealth.org
Celena Bodie, 654-786-6736, Cbodie@browardhealth.org/
- Recruiting
University of Florida Health Shands
Gainesville, Florida, 32608
Phuong Deleyrolle, 352-273-5529, phuong.deleyrolle@neurosurgery.ufl.edu
Victoria Hope, 352-273-9000, Victoria.Hope@neurosurgery.ufl.edu
- Recruiting
Baptist Health South Florida & Florida International University
Miami, Florida, 33176
Margarita Mederos, 786-596-1845, Margarita.mederos@BaptistHealth.net
Michael W. McDermott, MD
- Active, not recruiting
West Virginia University Rockefeller Neuroscience Center
Morgantown, West Virginia, 26506
- Active, not recruiting
Weill Cornell Medicine
New York, New York, 10065
- Recruiting
Advent Health
Orlando, Florida, 34747
Bhumi Patel, 407-609-4598, Bhumi.patel4@AdventHealth.com
Valeria Baldivieso, MD
- Recruiting
Tampa General Hospital
Tampa, Florida, 33612
Shalini Raj Nampally, 8138218513, snampally@tgh.org
Yarema Bezchlibnyk, MD
About this study
Official title: Assessment of Safety and Efficacy of ExAblate Blood-Brain Barrier Disruption for the Treatment of Patients With Probable 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 disrupt the blood-brain barrier (BBB) in patients with probable Alzheimer's Disease (AD).
Read the detailed description
This is a prospective, multi-center, single-arm study to evaluate the safety and efficacy of BBB disruption using the ExAblate Model 4000 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 up to 8 sites in the United States and will enroll up to 30 patients.
- Conditions
- Alzheimer Disease
- Being tested
- Blood Brain Barrier (BBB) Disruption
- Keywords
- Alzheimer Disease, Alzheimer Syndrome, Magnetic Resonance guided Focal Ultrasound (MRgFUS), Blood-Brain Barrier, ExAblate
- 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 | 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: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2018
- Study start28 Sep 2018
- Primary completionJan 2028 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Subjects who meet study eligibility will undergo treatment procedures
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- InSightec
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03671889
- Sponsor's protocol ID
- AL002
- Status last verified
- Jan 2026
- First submitted
- 3 Aug 2018
- Last updated
- 9 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Mehta RI, Carpenter JS, Mehta RI, Haut MW, Wang P, Ranjan M, Najib U, D'Haese PF, Rezai AR. Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer's disease. Fluids Barriers CNS. 2023 Jun 16;20(1):46. doi: 10.1186/s12987-023-00447-y.
PubMed 37328855Rezai AR, Ranjan M, Haut MW, Carpenter J, D'Haese PF, Mehta RI, Najib U, Wang P, Claassen DO, Chazen JL, Krishna V, Deib G, Zibly Z, Hodder SL, Wilhelmsen KC, Finomore V, Konrad PE, Kaplitt M; Alzheimer's Disease Neuroimaging Initiative. Focused ultrasound-mediated blood-brain barrier opening in Alzheimer's disease: long-term safety, imaging, and cognitive outcomes. J Neurosurg. 2022 Nov 4;139(1):275-283. doi: 10.3171/2022.9.JNS221565. Print 2023 Jul 1.
PubMed 36334289Mathew 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 34815790Mehta RI, Carpenter JS, Mehta RI, Haut MW, Ranjan M, Najib U, Lockman P, Wang P, D'haese PF, Rezai AR. Blood-Brain Barrier Opening with MRI-guided Focused Ultrasound Elicits Meningeal Venous Permeability in Humans with Early Alzheimer Disease. Radiology. 2021 Mar;298(3):654-662. doi: 10.1148/radiol.2021200643. Epub 2021 Jan 5.
PubMed 33399511
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Safety and Efficacy of ExAblate Blood-Brain Barrier Disruption for the Treatment of Patients With Probable Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT03671889
- Acronym / sponsor ID
- AL002
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer Disease, Alzheimer Syndrome, Magnetic Resonance guided Focal Ultrasound (MRgFUS), Blood-Brain Barrier, ExAblate
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- InSightecIndustry (pharma, biotech, devices)
- Study start
- 28 Sep 2018 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 14 Sep 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 disrupt the blood-brain barrier (BBB) in patients with probable Alzheimer's Disease (AD).
Detailed description
This is a prospective, multi-center, single-arm study to evaluate the safety and efficacy of BBB disruption using the ExAblate Model 4000 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 up to 8 sites in the United States and will enroll up to 30 patients.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Subjects who meet study eligibility will undergo treatment procedures
| Arm | Type | Receives |
|---|---|---|
| Blood Brain Barrier (BBB) Disruption | Experimental | Device: Blood Brain Barrier (BBB) DisruptionExAblate 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: 5 years
Rate of adverse events following each treatment through end of study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2026.
- Derived from this study: PubMed 37328855Mehta RI, Carpenter JS, Mehta RI, Haut MW, Wang P, Ranjan M, Najib U, D'Haese PF, Rezai AR. Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer's disease. Fluids Barriers CNS. 2023 Jun 16;20(1):46. doi: 10.1186/s12987-023-00447-y.
- Derived from this study: PubMed 36334289Rezai AR, Ranjan M, Haut MW, Carpenter J, D'Haese PF, Mehta RI, Najib U, Wang P, Claassen DO, Chazen JL, Krishna V, Deib G, Zibly Z, Hodder SL, Wilhelmsen KC, Finomore V, Konrad PE, Kaplitt M; Alzheimer's Disease Neuroimaging Initiative. Focused ultrasound-mediated blood-brain barrier opening in Alzheimer's disease: long-term safety, imaging, and cognitive outcomes. J Neurosurg. 2022 Nov 4;139(1):275-283. doi: 10.3171/2022.9.JNS221565. Print 2023 Jul 1.
- 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 33399511Mehta RI, Carpenter JS, Mehta RI, Haut MW, Ranjan M, Najib U, Lockman P, Wang P, D'haese PF, Rezai AR. Blood-Brain Barrier Opening with MRI-guided Focused Ultrasound Elicits Meningeal Venous Permeability in Humans with Early Alzheimer Disease. Radiology. 2021 Mar;298(3):654-662. doi: 10.1148/radiol.2021200643. Epub 2021 Jan 5.
- 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.
Delray Medical Center & Florida Atlantic University
Delray Beach, United States
Broward Health Medical Center & The University of Florida
Fort Lauderdale, United States
University of Florida Health Shands
Gainesville, United States
10 sites 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 10 sites in United States.
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: looking for participants now, as of the sponsor's last update on 9 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 10 sites in United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Device and procedure related adverse events (time frame: 5 years). 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 NCT03671889, which also lists 4 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 9 Jan 2026.