Mild Cognitive ImpairmentEarly Phase 1NCT05469009
Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer's Disease Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy
A Early Phase 1 study testing Aducanumab, Exablate Model 4000 Type 2 and Lecanemab in people with Mild Cognitive Impairment and Alzheimer Disease 1, run by Ali Rezai at 1 site in United States.
Trial summary
The purpose of this study is to assess the safety and feasibility of administering standard of care monoclonal antibody (mAb) infusion therapy in combination with opening the blood-brain barrier with the Exablate Model 4000 Type 2 device in patients with mild Alzheimer's disease (AD) or mild cognitive impairment (MCI). Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer Disease 1
- What is being tested?
- Aducanumab, Exablate Model 4000 Type 2 and Lecanemab
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jul 2022to Jul 2029
- Phase
- Early 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able and willing to give informed consent
- Probable mild cognitive impairment due to AD
- Modified Hachinski Ischemia Scale (MHIS) score of <= 4
- Mini Mental State Exam (MMSE) scores > 21+.
- Short form Geriatric Depression Scale (GDS) score of <= 7
- Amyloid PET scan consistent with the presence of β-amyloid (A+)
- Able to communicate sensations during the Exablate MRgFUS procedure
- Able to attend all study visits (i.e., life expectancy of 1 year or more)
Who cannot join
- MRI findings:
- Significant cardiac disease or unstable hemodynamic status
- History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage
- Known cerebral or systemic vasculopathy
- Significant depression (GDS > 7) and/or at potential risk of suicide (C-SSRS > 2)
- A severity score of 2 or more on any of the 'Delusions', 'Hallucinations' or 'Agitation/Aggression' subscales of the Neuropsychiatry Inventory (NPI-Q)
Show all 18Show fewer
- Known sensitivity/allergy to gadolinium(gadobutrol), DEFINITY or its components, or 18F-florbetaben.
- Known hypersensitivity to DEFINITY or its components.
- Any contraindications to MRI scanning
- Untreated, uncontrolled sleep apnea
- History of untreated or uncontrolled seizure disorder or epilepsy.
- Impaired renal function
- Does not have a reliable caregiver
- 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.
- Respiratory: chronic pulmonary disorders
- History of clinically significant recent drug or alcohol use disorder who may be at higher risk for seizure or infection.
- Positive human immunodeficiency virus (HIV) which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis.
- Potential blood-borne infections, which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess.
Trial locations and contacts
1 site in 1 country.
United States1 site
West Virginia University Rockefeller Neuroscience Institute
Morgantown, West Virginia, 26506
About this study
Official title: Assessment of Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for the Treatment of Patients With With Mild Cognitive Impairment (MCI) or Mild Alzheimer's Disease (AD) Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy
The purpose of this study is to assess the safety and feasibility of administering standard of care monoclonal antibody (mAb) infusion therapy in combination with opening the blood-brain barrier with the Exablate Model 4000 Type 2 device in patients with mild Alzheimer's disease (AD) or mild cognitive impairment (MCI).
Read the detailed description
The primary objectives of this study is to evaluate the safety and feasibility of BBBO (blood-brain barrier opening) using the Exablate Model 4000 Type 2 in the setting of standard aducanumab or lecanemab therapy among patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD) with confirmed β-amyloid, who are eligible for aducanumab or lecanemab infusion therapy, and to also evaluate the safety of the BBO procedure through patient examination (neurological and cognitive/behavioral) and MRI assessments during the treatment and follow-up.
The secondary objectives of this study is to determine the effect of BBBO in patients with MCI or mild AD treated with aducanumab or lecanemab on brain β-amyloid plaque measured by amyloid positron emission tomography (PET), as well as to assess the clinical impact of BBBO with standard aducanumab or lecanemab therapy, if any, as assessed with ADAS Cog 11 and MMSE over time following BBBO.
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease 1
- Being tested
- Aducanumab, Exablate Model 4000 Type 2, Lecanemab
- Medical subject headings
- Cognitive Dysfunction, Alzheimer disease type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AducanumabDrug
Also called Aduhelm
Standard aducanumab therapy will be given by intravenous infusion every 4 weeks for 6 cycles with blood brain barrier opening
Exablate Model 4000 Type 2Device
Also called Focused Ultrasound
The Exablate Model 4000 will be utilized for the BBBO (blood-brain barrier opening) after each cycle of Aducanumab or Lecanemab administered per label.
LecanemabDrug
Also called Leqembi
Standard lecanemab therapy will be given by intravenous infusion every 2 weeks for up to 6 cycles with blood brain barrier opening
| Study group | Role | What they receive |
|---|---|---|
| Infusion plus Exablate BBBO Treatment | Experimental | Intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS. Receives: Drug: Aducanumab; Device: Exablate Model 4000 Type 2; Drug: Lecanemab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment intervention related adverse events
The total number of adverse events following each treatment through end of the study
Measured: From baseline, up to 5 year post last treatment
Treatment intervention related serious adverse events
The total number of serious adverse events following each treatment through end of the study
Measured: From baseline, up to 5 year post last treatment
Secondary outcomes (3)
Beta-Amyloid plaques within the brain
Beta-Amyloid uptake value measured by Amyloid PET scan
Measured: From baseline, up to 5 year post last treatment
Cognitive performance (ADAS COG 11)
Change in cognitive performance using the Alzheimer's Disease Assessment Cognitive Subscale, rating scores from 0-70. The greater the dysfunction, the greater the score. A score of 70 represents the most severe impairment and 0 represents the least impairment.
Measured: From baseline, up to 5 year post last treatment
Cognitive performance (MMSE)
Change in cognitive performance using the Mini Mental Status Exam, rating scores from 0-30. 25 or higher being classed as normal. A score below 24 is considered abnormal, indicating possible cognitive impairment.
Measured: From baseline, up to 5 year post last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2022
- Study start14 Jul 2022
- Primary completionJul 2029 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ali Rezai
- Sponsor type
- University, hospital or other
- Collaborators
- InSightec
- Responsible party
- Sponsor-investigator, Ali Rezai, West Virginia University
- Investigators
- Ali Rezai, MD, FAANS, Principal investigator, WVU Rockerfeller Neuroscience Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05469009
- Sponsor's protocol ID
- 2110449196
- Status last verified
- Nov 2025
- First submitted
- 19 Jul 2022
- Last updated
- 22 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for the Treatment of Patients With With Mild Cognitive Impairment (MCI) or Mild Alzheimer's Disease (AD) Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy
- ClinicalTrials.gov ID
- NCT05469009
- Acronym / sponsor ID
- 2110449196
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease 1
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Ali RezaiUniversity, hospital or other
- Collaborators
- InSightec
- Study start
- 14 Jul 2022 (actual)
- Primary completion
- Jul 2029 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 21 Jul 2022 (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 assess the safety and feasibility of administering standard of care monoclonal antibody (mAb) infusion therapy in combination with opening the blood-brain barrier with the Exablate Model 4000 Type 2 device in patients with mild Alzheimer's disease (AD) or mild cognitive impairment (MCI).
Detailed description
The primary objectives of this study is to evaluate the safety and feasibility of BBBO (blood-brain barrier opening) using the Exablate Model 4000 Type 2 in the setting of standard aducanumab or lecanemab therapy among patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD) with confirmed β-amyloid, who are eligible for aducanumab or lecanemab infusion therapy, and to also evaluate the safety of the BBO procedure through patient examination (neurological and cognitive/behavioral) and MRI assessments during the treatment and follow-up.
The secondary objectives of this study is to determine the effect of BBBO in patients with MCI or mild AD treated with aducanumab or lecanemab on brain β-amyloid plaque measured by amyloid positron emission tomography (PET), as well as to assess the clinical impact of BBBO with standard aducanumab or lecanemab therapy, if any, as assessed with ADAS Cog 11 and MMSE over time following BBBO.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Infusion plus Exablate BBBO Treatment | Experimental | Drug: Aducanumab, Device: Exablate Model 4000 Type 2, Drug: LecanemabIntravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Able and willing to give informed consent
- Probable mild cognitive impairment due to AD
- Modified Hachinski Ischemia Scale (MHIS) score of <= 4
- Mini Mental State Exam (MMSE) scores > 21+.
- Short form Geriatric Depression Scale (GDS) score of <= 7
Key exclusion criteria (18 listed)
- MRI findings:
- Significant cardiac disease or unstable hemodynamic status
- History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage
- Known cerebral or systemic vasculopathy
- Significant depression (GDS > 7) and/or at potential risk of suicide (C-SSRS > 2)
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 |
|---|---|---|
| AducanumabAlso: AduhelmStandard aducanumab therapy will be given by intravenous infusion every 4 weeks for 6 cycles with blood brain barrier opening | Drug | Infusion plus Exablate BBBO Treatment |
| Exablate Model 4000 Type 2Also: Focused UltrasoundThe Exablate Model 4000 will be utilized for the BBBO (blood-brain barrier opening) after each cycle of Aducanumab or Lecanemab administered per label. | Device | Infusion plus Exablate BBBO Treatment |
| LecanemabAlso: LeqembiStandard lecanemab therapy will be given by intravenous infusion every 2 weeks for up to 6 cycles with blood brain barrier opening | Drug | Infusion plus Exablate BBBO Treatment |
Primary outcome
Treatment intervention related adverse events
Time frame: From baseline, up to 5 year post last treatment
The total number of adverse events following each treatment through end of the study
Treatment intervention related serious adverse events
Time frame: From baseline, up to 5 year post last treatment
The total number of serious adverse events following each treatment through end of the study
3 secondary outcomes
Beta-Amyloid plaques within the brain
Time frame: From baseline, up to 5 year post last treatment
Cognitive performance (ADAS COG 11)
Time frame: From baseline, up to 5 year post last treatment
Cognitive performance (MMSE)
Time frame: From baseline, up to 5 year post last treatment
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 22 Jan 2026.
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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.
Ali Rezai, MD, FAANS principal investigator
WVU Rockerfeller Neuroscience Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Aducanumab, Exablate Model 4000 Type 2 and Lecanemab in people with Mild Cognitive Impairment and Alzheimer Disease 1, run by Ali Rezai 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?
The sponsor lists 8 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 22 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 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
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?
Treatment intervention related adverse events (time frame: From baseline, up to 5 year post last treatment). The study lists 2 primary outcomes in all. 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 22 Jan 2026.