Alzheimer DiseaseNCT06474013
A Clinical Trial to Evaluate the Initial Safety and Efficacy of Repetitive BBB (Blood Brain Barrier) Disruption Using High Intensity Focused Ultrasound 'ExAblate 4000 Type 2.1' in Patients With Alzheimer's Disease
A study testing ExAblate 4000 Type 2.1 in people with Alzheimer Disease, run by Korea University Anam Hospital.
Trial summary
This clinical trial is designed to evaluate the initial safety and efficacy of opening the blood brain barrier (BBB) in patients with Alzheimer's disease using the ExAblate 4000 Type 2.1, a MR guided high-intensity focused ultrasound surgical device that disrupts brain tissue. 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?
- ExAblate 4000 Type 2.1
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2024to 31 Jul 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
- Age between 50 and 85 years
- Total score of 23 or less on the K-MMSE (Korean version of the mini mental state exam)
- Positive 18F-Florbetaben (FBB) PET scan
- Have mild cognitive impairment or dementia due to Alzheimer's disease, each of which must meet the criteria below.
- if mild cognitive impairment: amnestic mild cognitive impairment according to Peterson
- If dementia: probable Alzheimer's disease dementia, according to the national institute of aging and Alzheimer's association (NIA-AA).
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- If a subject is taking medication for Alzheimer's disease such as an acetyl-cholinesterase-inhibitor (AChEI) and/or memantine, etc., the subject should maintained the stable dosage for at least 3 months.
- A subject who is able to express regarding sensation during the application of an investigational medical device in a clinical trial
- A subject who has voluntarily decided to participate in this clinical trial and has given written informed consent
- A subject who is willing to adhere to the protocol
Who cannot join
- A severity score of 2 or more for any of the following items on the caregiver-administered neuropsychiatry inventory (CGA-NPI): "delusions," "hallucinations," or "agitation/aggression."
- Known sensitivity/allergy to or contraindication* to the MRI contrast agent gadolinium (Gadovist® ) or ultrasound contrast agent Definity®
- Have a standard contraindication to MR imaging, such as implanted metal devices that are incompatible with MRI.
- Sensitivity/allergy to or contraindication to local anesthetics and any anesthetic used when conscious sedation is required during application of an investigational medical device in a clinical trial
- Anyone who has MRI result as any of the following
- Severe ischemic changes* have been identified.
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- Significant ischemic changes: defined as a fazekas score of 3 or greater than 5 lacunes or greater than 3 cerebral microbleeds
- active or chronic infection/inflammation
- Acute or chronic bleeding
- Tumor/space-occupying lesion
- meningeal enhancement
- intracranial hypotension
- ≥30% of the skull area traversed by sonication is covered by scars, scalp disorder, or atrophic scalp.
- Have a history of seizure disorder or epilepsy that may be worsened by opening the blood-brain barrier
- Have a history of bleeding disorders or clotting disorders
- Have a serious heart condition or unstable blood flow (e.g., uncontrolled high blood pressure, arrhythmia, angina, etc.)
- Decreased renal function (glomerular filtration rate<30 mL/min/1.73 m )2
- Unable to target due to severe brain atrophy
- Patient who positive for human immunodeficiency virus (HIV) and is at increased risk for HIV encephalitis by HIV entry into the brain parenchyma
- Have a potential blood vessel-derived infection that can enter the brain parenchyma, resulting in meningitis or a brain abscess
- Carriers of the homozygosity apolipoprotein E allele (ApoE4), which is known to be associated with a thin blood-brain barrier.
- Pregnant or nursing women
- For women of childbearing potential* who agree to use a clinically appropriate method of birth control** for the duration of the clinical trial
- Definition of women of childbearing age: means women who have experienced menarche, have not been surgically sterilized (hysterectomy or bilateral oophorectomy), or are not post-menopausal, defined as amenorrhea for 12 months or more for no other reason.
- Clinically appropriate contraception: defined as "[intrauterine device (e.g., Loop, Mirena), chemical barrier method (spermicide), or subdermal implantable contraceptive device (e.g., Implanon)] + physical barrier method (male or female)" for women, tubal surgery, or laparoscopic contraception (a type of tubal ligation).
- Currently participating in another clinical trial or have participated in another clinical trial within 90 days of the screening date
- Other, if the investigator determines that participation in the clinical trial is inappropriate ethically or because it could affect the outcome of the clinical trial ☞ Specific reasons must be documented in the case report form.
About this study
Official title: Initial Safety and Efficacy of Repetitive BBB (Blood Brain Barrier) Disruption Using High Intensity Focused Ultrasound 'ExAblate 4000 Type 2.1' in Patients With Alzheimer's Disease: Single-center, Open, Prospective, Single-arm, Feasibility, Investigator-initiated Trial)
This clinical trial is designed to evaluate the initial safety and efficacy of opening the blood brain barrier (BBB) in patients with Alzheimer's disease using the ExAblate 4000 Type 2.1, a MR guided high-intensity focused ultrasound surgical device that disrupts brain tissue.
Read the detailed description
This clinical trial aims to evaluate the initial safety and efficacy of opening the blood brain barrier (BBB) in patients with Alzheimer's disease using the ExAblate 4000 Type 2.1, a MR guided high-intensity focused ultrasound surgical device that disrupts brain tissue. It is designed as a single-center, open, prospective, single-arm, feasibility, investigator-initiated trial. Patients with Alzheimer's disease who require opening of the blood-brain barrier will be referred to this clinical trial. Those who voluntarily sign a signed consent form after receiving a full explanation of the clinical trial undergo a screening test. Those who fulfill all inclusion/exclusion criteria will be enrolled in this clinical trial and assigned an enrollment number. Only subjects enrolled in this clinical trial will undergo BBB opening (blood brain barrier disruption) using ExAblate 4000 Type 2.1, a high-intensity focused ultrasound surgical device, to open the BBB by 40-60 cc. After completion of the procedure, the participants will receive follow-up observation for the procedure for at least 2 hours after the procedure. At this time, the investigator checks whether an adverse event that causes dropout, and if the subject is dropped out, follow-up observation of the adverse event continues.
- Conditions
- Alzheimer Disease
- Being tested
- ExAblate 4000 Type 2.1
- Keywords
- Blood Brain Barrier (BBB) Disruption, ExAblate 4000 Type 2.1
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExAblate 4000 Type 2.1Device
The ExAblate BBB disruption procedure will be performed with ExAblate 4000 type 2.1 system, and this will be performed 3 times every 2 months.
| Study group | Role | What they receive |
|---|---|---|
| Blood Brain Barrier (BBB) Disruption | Experimental | All participant in this arm will undergo 3 sessions of transcranial magnetic resonance guided focused ultrasound blood brain barrier disruption every 2 months. Receives: Device: ExAblate 4000 Type 2.1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in standardized uptake value ratio (SUVR) on FBB-PET
FBB (18 F-Florbetaben)-PET examination to identify amyloid beta protein (Aβ) plaques in the brain will be performed to compare and analyze the global and regional standard uptake value ratio (SUVR) of cerebellar gray matter as a reference before the first BBBD (Visit 1) and at 2 months after the third BBBD (Visit 13), as well as the global/regional standard uptake value ratio (SUVR) at the site of BBBD
Measured: Baseline and Day 14 following the third treatment
Secondary outcomes (5)
Percentage change in electroencephalography metrics (%)
To identify EEG changes in the subjects, EEG frequency bands (delta, theta, alpha, beta, gamma) in the EEG frequency bands (delta, theta, alpha, beta, gamma)* will be analyzed using functional connectivity analysis (coherence, COH, phase lag index, PLI) and graph theory analysis (clustering coefficient, global efficiency, characteristic path length, modularity) for the change from prior to the first BBBD (visit 1) to 14 days after first, second, and third BBBD (visit4, visit 8, and visit 12) and 2 months after third BBBD (visit 13).
Measured: Baseline and Day 14 following the first, second, third treatment, and 2 months following third treatment
CGA-NPI score change (points) and percent change (%)
To determine the cognitive function status of subjects, the caregiver-administered neuropsychiatric inventory (CGA-NPI) will be completed to examine the score and percentage of change in CGA-NPI scores from baseline (Visit 1) to 14 days after the first, second, and third BBBD (Visits 4, 8, and 12) and 2 months after the third BBBD (Visit 13), respectively.
Measured: Baseline and Day 14 following the first, second, third treatment, and 2 months following third treatment
K-MMSE test score change (points) and percent change (%)
To determine the cognitive function status of the subjects, the Korean version of mini mental state exam (K-MMSE) will be completed to examine the score and percentage change in K-MMSE scores from before the first BBBD (Visit 1) to 14 days after first, second, and third BBBD (Visits 4, 8, and 12) and 2 months after third BBBD (Visit 13), respectively.
Measured: Baseline and Day 14 following the first, second, third treatment, and 2 months following third treatment
SNSB Test Score Change (points) and Percent Change (%)
To determine the cognitive function status of the subjects, the Seoul neuropsychological screening battery (SNSB) test will be used to examine the score and percent change in SNSB scores from before the first BBBD (Visit 1) to 2 months after the third BBBD (Visit 13).
Measured: Baseline and 2 months following the third treatment
Degree of blood-brain barrier opening (cm3)
The degree of blood-brain barrier opening will be assessed by comparing contrast-enhanced MR images before the first BBBD (visit 1) and after the first, second and third BBBD (visit 3, visit 6, visit 10). To demonstrate BBB opening by BBBD, the volume of the area where the blood-brain barrier is opened (cm3) will be determined.
Measured: first treatment and 2 months, 4 months following the first treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2024
- Study start1 Sep 2024 (estimated)
- Primary completion30 Sep 2024 (estimated)
- Study completion31 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Korea University Anam Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chang, Jin Woo, Korea University Anam Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06474013
- Sponsor's protocol ID
- KUAHAD-01
- Status last verified
- Aug 2024
- First submitted
- 19 Jun 2024
- Last updated
- 21 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Initial Safety and Efficacy of Repetitive BBB (Blood Brain Barrier) Disruption Using High Intensity Focused Ultrasound 'ExAblate 4000 Type 2.1' in Patients With Alzheimer's Disease: Single-center, Open, Prospective, Single-arm, Feasibility, Investigator-initiated Trial)
- ClinicalTrials.gov ID
- NCT06474013
- Acronym / sponsor ID
- KUAHAD-01
- Conditions
- Alzheimer Disease
- Keywords
- Blood Brain Barrier (BBB) Disruption, ExAblate 4000 Type 2.1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Korea University Anam HospitalUniversity, hospital or other
- Study start
- 1 Sep 2024 (estimated)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 31 Jul 2025 (estimated)
- First posted
- 25 Jun 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.
This clinical trial is designed to evaluate the initial safety and efficacy of opening the blood brain barrier (BBB) in patients with Alzheimer's disease using the ExAblate 4000 Type 2.1, a MR guided high-intensity focused ultrasound surgical device that disrupts brain tissue.
Detailed description
This clinical trial aims to evaluate the initial safety and efficacy of opening the blood brain barrier (BBB) in patients with Alzheimer's disease using the ExAblate 4000 Type 2.1, a MR guided high-intensity focused ultrasound surgical device that disrupts brain tissue. It is designed as a single-center, open, prospective, single-arm, feasibility, investigator-initiated trial. Patients with Alzheimer's disease who require opening of the blood-brain barrier will be referred to this clinical trial. Those who voluntarily sign a signed consent form after receiving a full explanation of the clinical trial undergo a screening test. Those who fulfill all inclusion/exclusion criteria will be enrolled in this clinical trial and assigned an enrollment number. Only subjects enrolled in this clinical trial will undergo BBB opening (blood brain barrier disruption) using ExAblate 4000 Type 2.1, a high-intensity focused ultrasound surgical device, to open the BBB by 40-60 cc. After completion of the procedure, the participants will receive follow-up observation for the procedure for at least 2 hours after the procedure. At this time, the investigator checks whether an adverse event that causes dropout, and if the subject is dropped out, follow-up observation of the adverse event continues.
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: ExAblate 4000 Type 2.1All participant in this arm will undergo 3 sessions of transcranial magnetic resonance guided focused ultrasound blood brain barrier disruption every 2 months. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age between 50 and 85 years
- Total score of 23 or less on the K-MMSE (Korean version of the mini mental state exam)
- Positive 18F-Florbetaben (FBB) PET scan
- Have mild cognitive impairment or dementia due to Alzheimer's disease, each of which must meet the criteria below.
- If a subject is taking medication for Alzheimer's disease such as an acetyl-cholinesterase-inhibitor (AChEI) and/or memantine, etc., the subject should maintained the stable dosage for at least 3 months.
Key exclusion criteria (27 listed)
- A severity score of 2 or more for any of the following items on the caregiver-administered neuropsychiatry inventory (CGA-NPI): "delusions," "hallucinations," or "agitation/aggression."
- Known sensitivity/allergy to or contraindication* to the MRI contrast agent gadolinium (Gadovist® ) or ultrasound contrast agent Definity®
- Have a standard contraindication to MR imaging, such as implanted metal devices that are incompatible with MRI.
- Sensitivity/allergy to or contraindication to local anesthetics and any anesthetic used when conscious sedation is required during application of an investigational medical device in a clinical trial
- Anyone who has MRI result as any of the following
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 |
|---|---|---|
| ExAblate 4000 Type 2.1The ExAblate BBB disruption procedure will be performed with ExAblate 4000 type 2.1 system, and this will be performed 3 times every 2 months. | Device | Blood Brain Barrier (BBB) Disruption |
Primary outcome
Change in standardized uptake value ratio (SUVR) on FBB-PET
Time frame: Baseline and Day 14 following the third treatment
FBB (18 F-Florbetaben)-PET examination to identify amyloid beta protein (Aβ) plaques in the brain will be performed to compare and analyze the global and regional standard uptake value ratio (SUVR) of cerebellar gray matter as a reference before the first BBBD (Visit 1) and at 2 months after the third BBBD (Visit 13), as well as the global/regional standard uptake value ratio (SUVR) at the site of BBBD
5 secondary outcomes
Percentage change in electroencephalography metrics (%)
Time frame: Baseline and Day 14 following the first, second, third treatment, and 2 months following third treatment
CGA-NPI score change (points) and percent change (%)
Time frame: Baseline and Day 14 following the first, second, third treatment, and 2 months following third treatment
K-MMSE test score change (points) and percent change (%)
Time frame: Baseline and Day 14 following the first, second, third treatment, and 2 months following third treatment
SNSB Test Score Change (points) and Percent Change (%)
Time frame: Baseline and 2 months following the third treatment
Degree of blood-brain barrier opening (cm3)
Time frame: first treatment and 2 months, 4 months following the first treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Individual participant dataSharing planned: Undecided
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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.
Questions about this trial
What is this clinical trial studying?
A study testing ExAblate 4000 Type 2.1 in people with Alzheimer Disease, run by Korea University Anam Hospital.
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 10 inclusion and 27 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: status not confirmed, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
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?
Change in standardized uptake value ratio (SUVR) on FBB-PET (time frame: Baseline and Day 14 following the third 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 21 Aug 2024.