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

Single-center, Open, Prospective, Single-arm, Feasibility, Investigator-initiated Trail for 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

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.

Study Overview

• Status: Unknown
• Conditions: Alzheimer Disease
• Intervention / Treatment: Device: transcranial magnetic resonance guided focused ultrasound BBB disruption

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Department of Neurosurgery, Yonsei University College of Medici

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Device: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events safety profile	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.	6 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Jin Woo Chang, Severance Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2020
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: August 19, 2020
• First Submitted That Met QC Criteria: August 23, 2020
• First Posted (Actual): August 25, 2020

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 23, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 1-2019-0095

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No