Assessment of Initial Efficacy and Safety of High Intensity Focused Ultrasound 'ExAblate 4000 Type 2' for Blood Brain Barrier Disruption in Patients With Alzheimer's Disease

NCT ID: NCT04526262

Last Updated: 2020-08-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-10
• Study Completion Date: 2020-12-31

Brief Summary

The proposed study is to evaluate initial efficacy and safety of the BBB disruption with transcranial MRI-guided focused ultrasound (ExAblate 4000 type 2.0) in patients with Alzheimer's disease.

This study iw designed as a prospective, single-site, single-aarm, nonrandomized study. Assessments will be made before and three months after 2 sessions of BBB disruption with radiologic, nuclear medicine imaging and neurophysiological examinations. Relative safety will be evaluated using a common description of Significant Clinical Complications for patients treated in this study.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BBB disruption

All participant in this arm will undergo 2 sessions of transcranial magnetic resonance guided focused ultrasound blood brain barrier disruption every 3 months.

Group Type: EXPERIMENTAL

transcranial magnetic resonance guided focused ultrasound BBB disruption

Intervention Type: DEVICE

The ExAblate BBB disruption procedure will be performed with ExAblate 4000 type 2.0 system, and this will be performed twice every 3 months.

Interventions

transcranial magnetic resonance guided focused ultrasound BBB disruption

The ExAblate BBB disruption procedure will be performed with ExAblate 4000 type 2.0 system, and this will be performed twice every 3 months.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age between 50 and 85 years, inclusive.
• Total score of 23 or less on the Korean version of Mini Mental state Exam (K-MMSE)
• FBB (18F-Florbetaben)-PET test result positive
• FDB (18F-Fluorodeoxyglucose)-PET test results suspected of Alzheimer disease-induced neurodegeneration
• Mild cognitive impairment or dementia caused by Alzheimer's disease
• A participant who has been given a drug at a stable dose for at least three months to improve symptoms of Alzheimer's disease
• Able to communicate during the ExAblate BBB disruption procedure
• Able and willing to give informed consent
• Able to attend all study visits

Exclusion Criteria

• CGA-NPI (Caregiver-Administrated Neuropsychiatry Inventory) severity score of more than 2 points for any of "Delusion", "Hallucination" or "Agitation/Aggression"
• Known sensitivity/allergy or contraindications to MRI contrast agent(Gadovist®) or the ultrasound contrast agent (Definity®)
• Contraindications to MRI such as non-MRI compatible implanted devices.
• Any of the following items in MRI

1. severe ischemic changes

2. active or chronic infection/inflammation

3. acute or chronic hemorrhage

4. tumor/space occupying lesion

5. meningeal enhancement

6. intracranial hypotension

• More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp
• Active seizure disorder or epilepsy (seizures despite medical treatment)
• History of a bleeding disorder, coagulopathy
• Cardiac disease or unstable hemodynamics
• Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2
• Severe brain atrophy
• HIV (Human immunodeficiency virus) positive, who have a high probability of developing HIV encephalitis due to the influx of HIV in to the brain parenchyma
• Subjects with evidence of cranial or systemic infection
• A homozygosity of Apolipoprotein E allele (ApoE4) known to have a thin blood-brain barrier
• Positive pregnancy test (women of childbearing potential)
• A participant in other clinical trials or have experience in other clinical trials within 90 days from the screening date

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jin Woo Chang

Role: PRINCIPAL_INVESTIGATOR

Severance Hospital

Locations

Department of Neurosurgery, Yonsei University College of Medici

Seoul, , South Korea

Countries

South Korea

Other Identifiers

1-2019-0095

Identifier Type: -

Identifier Source: org_study_id