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
NCT Number: NCT06474013
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Alzheimer Disease
Interventions: DEVICE: ExAblate 4000 Type 2.1
Sponsor: Korea University Anam Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 15
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2025-07-31

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.

Primary Outcome Measures: 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, Baseline and Day 14 following the third treatment
Secondary Outcome Measures: 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)., 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., 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., 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)., 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., first treatment and 2 months, 4 months following the first treatment