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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
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.
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
Time frame: Baseline and Day 14 following the third treatment
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).
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 (%)
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.
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 (%)
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.
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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 (%)
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).
Time frame: 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.
Time frame: first treatment and 2 months, 4 months following the first treatment