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

NCT06474013 | Not Yet Recruiting

• 1 other identifier: KUAHAD-01
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Alzheimer Disease

Keywords

Blood Brain Barrier (BBB) Disruption; ExAblate 4000 Type 2.1

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Percentage change in electroencephalography metrics (%)

  Baseline and Day 14 following the first, second, third treatment, and 2 months following third treatment

• CGA-NPI score change (points) and percent change (%)

  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 (%)

  Baseline and Day 14 following the first, second, third treatment, and 2 months following third treatment

• SNSB Test Score Change (points) and Percent Change (%)

  Baseline and 2 months following the third treatment

• Degree of blood-brain barrier opening (cm3)

  first treatment and 2 months, 4 months following the first treatment

Study Arms (1)

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.

Device: ExAblate 4000 Type 2.1

Interventions

ExAblate 4000 Type 2.1 DEVICE

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.

Blood Brain Barrier (BBB) Disruption

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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.
• \*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

Sponsors & Collaborators

• Korea University Anam Hospital: lead

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 19, 2024
• First Posted: June 25, 2024
• Study Start: September 1, 2024
• Primary Completion: September 30, 2024
• Study Completion: July 31, 2025
• Last Updated: August 21, 2024

Record last verified: 2024-08