Alzheimer Disease, Early OnsetPhase 1FUS-ADNCT06600880
Neuronavigation-guided FUS-induced BBB Opening in Alzheimer's Disease Patients and Its Effects on Brain Amyloid and Tau
A Phase 1 study testing Neuronavigation-guided single-element focused ultrasound transducer, Lumason and Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents in people with Alzheimer Disease, Early Onset, run by Columbia University at 1 site in United States.
Trial summary
The primary purpose of this phase 1b study is to further assess the safety and reversibility of focused ultrasound induced blood-brain barrier opening (FUS-BBBO) in participants with Alzheimer´s Disease (AD) using a single-element transducer with neuronavigation guidance. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer Disease, Early Onset
- What is being tested?
- Neuronavigation-guided single-element focused ultrasound transducer, Lumason and Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2027to Dec 2028
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria. AD patients will be recruited in person and have to be over 50 years of age and able to give consent. Patients diagnosed with MCI or AD will be included in our study. Other more severe symptomatic patients will be eligible to enroll, as long as they have the ability to consent for their participation. Screening is essential and will be performed by our collaborator and neurologist of the study, Dr. Lawrence Honig, MD at the Taub Institute of Alzheimer's Disease and Aging at Columbia. After the initial screening we will acquire MRI scans as part of the study and finalize enrollment or exclusion of the patient. Inclusion criteria thus include:
- Age greater than 50 years old.
- Diagnosis of MCI or AD. All following criteria must be met:
- MMSE score between 12 and 26.
- Modified Hachinski Ischemia Scale (MHIS) score of <= 4
- Short form Geriatric Depression Scale (GDS) score of <= 6.
- PET scan confirming amyloid plaque load using Amyvid (18F-Florbetapir).
- PET scan confirming tau positivity in the frontal lobe using MK-6240 (F18-Florquinitau).
- Ability to provide informed consent.
Exclusion Criteria. Exclusion criteria include surgeries and other pathologies not associated with AD, as outlined in the following list:
- Prior administration of any amyloid-reducing agent such as aducanumab or lecanemab.
- Contraindication for MRI.
- Contra-indication history or hypersensitivity to MRI contrast agents (e.g., Dotarem) or microbubbles (e.g., Definity, Lumason), including polyethylene glycol (PEG) allergy.
- Prior brain surgery, including deep brain stimulation.
- Metallic implants.
- Abnormal coagulation profile (significant abnormality in PT, PTT, or platelets).
- Anticoagulant therapy.
- History of seizure disorder.
- Brain atrophy to a degree that would interfere with ultrasound delivery.
- Inability to comply with the procedures of the protocol, including follow-up scans.
- Women with capacity to bear children or lactating.
- Impaired renal function with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 provided by a standard blood test 2-4 weeks prior to the ultrasound treatment.
- Active infection/inflammation.
- Acute or chronic hemorrhages, i.e. > 4 lobar microbleeds, or an area of siderosis or macrohemorrhages.
- Tumors or space-occupying lesions of significance.
- Any uncontrolled medical disorder that might interfere with the ability to safely perform the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
Sergio Jimenez Gambin, PhD, 929-545-5655 ext. 1, sj3044@columbia.edu
About this study
Official title: Neuronavigation-guided Focused Ultrasound-induced Blood-brain Barrier Opening in Alzheimer's Disease Patients and Its Effects on Brain Amyloid and Tau
The primary purpose of this phase 1b study is to further assess the safety and reversibility of focused ultrasound induced blood-brain barrier opening (FUS-BBBO) in participants with Alzheimer´s Disease (AD) using a single-element transducer with neuronavigation guidance. Preliminary results from our phase 1a study demonstrate that our neuronavigation-guided FUS system was capable of safely and transiently open the BBB in participants with AD. The information collected in this new study may be used to design future clinical trials to ultimately provide a viable alternative for treatment of AD in a safe and noninvasive manner.
Our secondary objective includes the assessment of the therapeutic efficacy of FUS-BBBO in reducing amyloid beta and neurofibrillary tangles, the main hallmark pathologies of AD, using PET tracers. Based on our preclinical studies in AD transgenic mouse models, FUS-BBBO alone was able to reduce both the amyloid beta and tau protein load, resulting in improvements in behavioral tasks assessing memory. Therefore, in this new study, the effect of FUS-BBBO on the amyloid beta and tau protein load in patients with AD will be assessed through the use of PET tracers.
Read the detailed description
Regarding the primary purpose of this study, the human module for the neuronavigator was implemented in our phase 1a trial, and initial feasibility and safety in a small cohort of AD patients had been tested, with a fast procedural time that required no anesthesia.
Regarding the secondary objective, both amyloid beta and tau protein load in the brain will be assessed at baseline (before FUS-BBBO treatment), and 3-weeks and 3-months after FUS-BBBO treatment, to assess any short-term or long-term changes, respectively.
- Conditions
- Alzheimer Disease, Early Onset
- Being tested
- Neuronavigation-guided single-element focused ultrasound transducer, Lumason, Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents, Positron Emission Tomography (PET), Amyvid
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neuronavigation-guided single-element focused ultrasound transducerDevice
Non-invasive focused ultrasound-induced blood-brain barrier opening will be attempted using a single-element transducer, guided with a neuronavigation system.
LumasonDrug
New packages of Lumason microbubbles will be shipped from Bracco Diagnostics Inc. and will be used in conjunction with the ultrasound transducer to temporarily open the BBB. Lumason microbubbles will be freshly activated before treatment sonication and will be drawn using a 10-ml syringe to reach the desired dosage of 0.1mL/kg right before the intravenous injection.
Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agentsOther
A high-resolution MRI (with and without gadolinium (Dotarem) contrast agent) will be acquired prior to BBB opening on the GE SIGNATM Premier (3T) (same scanner as in the NHP study) for pre-treatment planning and screening purposes. Then, a second MRI (with and without gadolinium) will be acquired and read by a Board-Certified Radiologist immediately after the treatment sonication in order to assess the BBB opening and safety. Finally, a final follow-up MRI (with and without gadolinium) will be conducted 3 days (±1 day) after the treatment to confirm BBB closing and/or safety. This will be read by a Board-Certified Radiologist as well.
All MRI procedures will be performed at the CUIMC/Neurological Institute of New York.
Positron Emission Tomography (PET)Radiation
A first PET/CT scan with Amyvid (18F-Florbetapir) and MK-6240 (F18-Florquinitau) tracers will be performed on the SIEMENS Biograph 64 to assess the baseline amyloid plaque load and tau load before the treatment, respectively. Finally, two follow-up PET/CT scans will be conducted 3 weeks (±1 week) and 3 months (±2 weeks) post-treatment to assess amyloid plaque load (using Amyvid) and tau load (using MK-6240).
AmyvidDrug
Also called 18F-Florbetapir
Amyloid PET tracer Amyvid (18F- Florbetapir) will be stored in their original container with proper radiation shielding at 25 °C and only handled by properly trained personnel in the handling and administration of radioactive materials, which requires employing proper radiation protection procedures.
MK-6240Drug
[18F]MK-6240 will be synthesized, purified, and formulated at the local radiochemistry synthesis laboratory and will be administered as a sterile, pyrogen-free solution by IV injection. The radiotracer [18F]MK-6240 is supplied in a sterile, ready-to-use solution, direct from the Columbia University PET Center. It is supplied for a targeted calibration time, the precise volume to be administered at a given time can be calculated based on the decay of F-18. Only personnel properly trained in the handling and administration of radioactive materials should handle [18F]MK-6240. Usual radiation protection procedures should be used for handling radiotracers, including shielding (lead or tungsten containers/shields), and personal protective equipment including gloves. There are no specific procedures required for the handling of [18F]MK-6240. The expiry of [18F]MK-6240 is eight hours from the time at End of Synthesis (EOS).
DotaremDrug
FDA-approved medication. Dotarem will be handled in accordance with the CUMC Research Pharmacy procedures and NYP policy P168, Version 4. Dotarem will be used according to its labeling. 0.2 ml/kg.
Blood drawDiagnostic test
Blood samples will be collected through an intravenous catheter or a finger prick during screening, on the day of the FUS treatment and the follow up examinations (week 3 and month 3). These samples will be processed to assess any blood content changes induced by the focused ultrasound treatment.
UR5eDevice
Universal Robots robotic arm used for the accurate positioning of the neuronavigation-guided single-element focused ultrasound transducer with respect to the patient's head.
Urine testDiagnostic test
Urine test required following the MRI and PET Centers policy used clinically for pregnancy screening
| Study group | Role | What they receive |
|---|---|---|
| Focused ultrasound treatment | Experimental | Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. Receives: Device: Neuronavigation-guided single-element focused ultrasound transducer; Drug: Lumason; Other: Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents; Radiation: Positron Emission Tomography (PET); Drug: Amyvid; Drug: MK-6240; Drug: Dotarem; Diagnostic Test: Blood draw; Device: UR5e; Diagnostic Test: Urine test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Individuals With Successful Opening of the BBB
Opening the BBB successfully in all the patients, while obtaining a volume of BBB opened being similar and consistent for all patients
Measured: 4 days, including the day of treatment
Secondary outcomes (3)
Total Number of Safety Events Related to Opening of BBB
Showing safe BBB opening for all patients without any Adverse Event nor Serious Adverse Event, and showing its safety as well in 3 days after treatment
Measured: 4 days, including the day of treatment
Percent Change in Amyloid PET Signal Intensity
A moderately shown in our previous clinical trial study, we expect to observe a slowed down increase of Amyloid protein load after the treatment on the two follow-ups performed at 3 weeks (±1 week) and 3 months (±2 week) after treatment.
Measured: 3 months (±2 weeks)
Percent Change in MK-6240 PET Signal Intensity
As shown in our previous studies in mice, we expect to observe a slowed down increase or reduction on Tau protein load after the treatment on the two follow-ups performed at 3 weeks (±1 week) and 3 months (±2 week) after treatment.
Measured: 3 months (±2 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study startAug 2027 (estimated)
- Primary completionJul 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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 1
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Grace McIlvain, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06600880
- Sponsor's protocol ID
- AAAV4854
- Acronym
- FUS-AD
- Status last verified
- May 2026
- First submitted
- 11 Sep 2024
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No: No individual participant data (IPD) will be shared with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuronavigation-guided Focused Ultrasound-induced Blood-brain Barrier Opening in Alzheimer's Disease Patients and Its Effects on Brain Amyloid and Tau
- ClinicalTrials.gov ID
- NCT06600880
- Acronym / sponsor ID
- FUS-AD / AAAV4854
- Conditions
- Alzheimer Disease, Early Onset
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Aug 2027 (estimated)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 19 Sep 2024 (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 primary purpose of this phase 1b study is to further assess the safety and reversibility of focused ultrasound induced blood-brain barrier opening (FUS-BBBO) in participants with Alzheimer´s Disease (AD) using a single-element transducer with neuronavigation guidance. Preliminary results from our phase 1a study demonstrate that our neuronavigation-guided FUS system was capable of safely and transiently open the BBB in participants with AD. The information collected in this new study may be used to design future clinical trials to ultimately provide a viable alternative for treatment of AD in a safe and noninvasive manner.
Our secondary objective includes the assessment of the therapeutic efficacy of FUS-BBBO in reducing amyloid beta and neurofibrillary tangles, the main hallmark pathologies of AD, using PET tracers. Based on our preclinical studies in AD transgenic mouse models, FUS-BBBO alone was able to reduce both the amyloid beta and tau protein load, resulting in improvements in behavioral tasks assessing memory. Therefore, in this new study, the effect of FUS-BBBO on the amyloid beta and tau protein load in patients with AD will be assessed through the use of PET tracers.
Detailed description
Regarding the primary purpose of this study, the human module for the neuronavigator was implemented in our phase 1a trial, and initial feasibility and safety in a small cohort of AD patients had been tested, with a fast procedural time that required no anesthesia.
Regarding the secondary objective, both amyloid beta and tau protein load in the brain will be assessed at baseline (before FUS-BBBO treatment), and 3-weeks and 3-months after FUS-BBBO treatment, to assess any short-term or long-term changes, respectively.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Focused ultrasound treatment | Experimental | Device: Neuronavigation-guided single-element focused ultrasound transducer, Drug: Lumason, Other: Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents, Radiation: Positron Emission Tomography (PET), Drug: Amyvid, Drug: MK-6240, Drug: Dotarem, Diagnostic Test: Blood draw, Device: UR5e, Diagnostic Test: Urine testNeuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Neuronavigation-guided single-element focused ultrasound transducerNon-invasive focused ultrasound-induced blood-brain barrier opening will be attempted using a single-element transducer, guided with a neuronavigation system. | Device | Focused ultrasound treatment |
| LumasonNew packages of Lumason microbubbles will be shipped from Bracco Diagnostics Inc. and will be used in conjunction with the ultrasound transducer to temporarily open the BBB. Lumason microbubbles will be freshly activated before treatment sonication and will be drawn using a 10-ml syringe to reach the desired dosage of 0.1mL/kg right before the intravenous injection. | Drug | Focused ultrasound treatment |
| Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agentsA high-resolution MRI (with and without gadolinium (Dotarem) contrast agent) will be acquired prior to BBB opening on the GE SIGNATM Premier (3T) (same scanner as in the NHP study) for pre-treatment planning and screening purposes. Then, a second MRI (with and without gadolinium) will be acquired and read by a Board-Certified Radiologist immediately after the treatment sonication in order to assess the BBB opening and safety. Finally, a final follow-up MRI (with and without gadolinium) will be conducted 3 days (±1 day) after the treatment to confirm BBB closing and/or safety. This will be read by a Board-Certified Radiologist as well. All MRI procedures will be performed at the CUIMC/Neurological Institute of New York. | Other | Focused ultrasound treatment |
| Positron Emission Tomography (PET)A first PET/CT scan with Amyvid (18F-Florbetapir) and MK-6240 (F18-Florquinitau) tracers will be performed on the SIEMENS Biograph 64 to assess the baseline amyloid plaque load and tau load before the treatment, respectively. Finally, two follow-up PET/CT scans will be conducted 3 weeks (±1 week) and 3 months (±2 weeks) post-treatment to assess amyloid plaque load (using Amyvid) and tau load (using MK-6240). | Radiation | Focused ultrasound treatment |
| AmyvidAlso: 18F-FlorbetapirAmyloid PET tracer Amyvid (18F- Florbetapir) will be stored in their original container with proper radiation shielding at 25 °C and only handled by properly trained personnel in the handling and administration of radioactive materials, which requires employing proper radiation protection procedures. | Drug | Focused ultrasound treatment |
| MK-6240[18F]MK-6240 will be synthesized, purified, and formulated at the local radiochemistry synthesis laboratory and will be administered as a sterile, pyrogen-free solution by IV injection. The radiotracer [18F]MK-6240 is supplied in a sterile, ready-to-use solution, direct from the Columbia University PET Center. It is supplied for a targeted calibration time, the precise volume to be administered at a given time can be calculated based on the decay of F-18. Only personnel properly trained in the handling and administration of radioactive materials should handle [18F]MK-6240. Usual radiation protection procedures should be used for handling radiotracers, including shielding (lead or tungsten containers/shields), and personal protective equipment including gloves. There are no specific procedures required for the handling of [18F]MK-6240. The expiry of [18F]MK-6240 is eight hours from the time at End of Synthesis (EOS). | Drug | Focused ultrasound treatment |
| DotaremFDA-approved medication. Dotarem will be handled in accordance with the CUMC Research Pharmacy procedures and NYP policy P168, Version 4. Dotarem will be used according to its labeling. 0.2 ml/kg. | Drug | Focused ultrasound treatment |
| Blood drawBlood samples will be collected through an intravenous catheter or a finger prick during screening, on the day of the FUS treatment and the follow up examinations (week 3 and month 3). These samples will be processed to assess any blood content changes induced by the focused ultrasound treatment. | Diagnostic test | Focused ultrasound treatment |
| UR5eUniversal Robots robotic arm used for the accurate positioning of the neuronavigation-guided single-element focused ultrasound transducer with respect to the patient's head. | Device | Focused ultrasound treatment |
| Urine testUrine test required following the MRI and PET Centers policy used clinically for pregnancy screening | Diagnostic test | Focused ultrasound treatment |
Primary outcome
Total Number of Individuals With Successful Opening of the BBB
Time frame: 4 days, including the day of treatment
Opening the BBB successfully in all the patients, while obtaining a volume of BBB opened being similar and consistent for all patients
3 secondary outcomes
Total Number of Safety Events Related to Opening of BBB
Time frame: 4 days, including the day of treatment
Percent Change in Amyloid PET Signal Intensity
Time frame: 3 months (±2 weeks)
Percent Change in MK-6240 PET Signal Intensity
Time frame: 3 months (±2 weeks)
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 13 May 2026.
- Individual participant dataSharing planned: No. No individual participant data (IPD) will be shared with other researchers.
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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.
Grace McIlvain, PhD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Neuronavigation-guided single-element focused ultrasound transducer, Lumason and Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents in people with Alzheimer Disease, Early Onset, run by Columbia University at 1 site 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?
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: opening soon, as of the sponsor's last update on 13 May 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 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Sergio Jimenez Gambin, PhD (9295455655 ext. 1, sj3044@columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Number of Individuals With Successful Opening of the BBB (time frame: 4 days, including the day of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 May 2026.