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

Yonsei University

Status: Unknown

Conditions: Alzheimer Disease

Treatments: Device: transcranial magnetic resonance guided focused ultrasound BBB disruption

Study type: Interventional

Funder types: Other

Identifiers

NCT04526262

1-2019-0095

Details and patient eligibility

About

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.

Enrollment: 6 estimated patients

Sex: All

Ages: 50 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

BBB disruption

Experimental group

Description:

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

Treatment:

Device: transcranial magnetic resonance guided focused ultrasound BBB disruption