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

Not Applicable

• Conditions: Alzheimer Disease
• Interventions: Device: transcranial magnetic resonance guided focused ultrasound BBB disruption

• Registration Number: NCT04526262
• Lead Sponsor: Yonsei University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-04-10
• Status Verified: 2020-08
• Study First Submitted: 2020-08-19
• Study First Submitted QC: 2020-08-23
• Last Update Submitted: 2020-08-23
• Study First Posted: 2020-08-25
• Last Update Posted: 2020-08-25
• Primary Completion: 2020-12
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 6

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BBB disruption	transcranial magnetic resonance guided focused ultrasound 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.

Primary Outcome Measures

Name	Time	Method
Adverse events safety profile	6 months	The type and severity of post-procedure adverse events will be assessed for overall safety. Safety of the BBBD procedure will be evaluated through patient examination and MRI assessements during the treatment and by their standard care of follow-up MRI scans and clinical visits.

Secondary Outcome Measures

Name	Time	Method
Efficacy of BBB disruption : evaluated by nuclear medicine imaging	6 months	The efficacy of BBB disruption in Alzheimer's disease will be evaluated by radiologic, nuclear medicine imaging and neurophysiological examination.
Efficacy of BBB disruption : evaluated by neurophysiological examination	6 months	The efficacy of BBB disruption in Alzheimer's disease will be evaluated by radiologic, nuclear medicine imaging and neurophysiological examination.
Efficacy of BBB disruption : evaluated by radiologic imaging	6 months	The efficacy of BBB disruption in Alzheimer's disease will be evaluated by radiologic, nuclear medicine imaging and neurophysiological examination.

Trial Locations

Locations (1)

Department of Neurosurgery, Yonsei University College of Medici; 🇰🇷 Seoul, Korea, Republic of