search
Back to results

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

Primary Purpose

Alzheimer Disease

Status
Unknown status
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
transcranial magnetic resonance guided focused ultrasound BBB disruption
Sponsored by
Yonsei University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Department of Neurosurgery, Yonsei University College of Medici

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BBB disruption

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
August 19, 2020
Last Updated
August 23, 2020
Sponsor
Yonsei University
search

1. Study Identification

Unique Protocol Identification Number
NCT04526262
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 10, 2020 (Actual)
Primary Completion Date
December 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
BBB disruption
Arm Type
Experimental
Arm Description
All participant in this arm will undergo 2 sessions of transcranial magnetic resonance guided focused ultrasound blood brain barrier disruption every 3 months.
Intervention Type
Device
Intervention Name(s)
transcranial magnetic resonance guided focused ultrasound BBB disruption
Intervention Description
The ExAblate BBB disruption procedure will be performed with ExAblate 4000 type 2.0 system, and this will be performed twice every 3 months.
Primary Outcome Measure Information:
Title
Adverse events safety profile
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Efficacy of BBB disruption : evaluated by radiologic imaging
Description
The efficacy of BBB disruption in Alzheimer's disease will be evaluated by radiologic, nuclear medicine imaging and neurophysiological examination.
Time Frame
6 months
Title
Efficacy of BBB disruption : evaluated by nuclear medicine imaging
Description
The efficacy of BBB disruption in Alzheimer's disease will be evaluated by radiologic, nuclear medicine imaging and neurophysiological examination.
Time Frame
6 months
Title
Efficacy of BBB disruption : evaluated by neurophysiological examination
Description
The efficacy of BBB disruption in Alzheimer's disease will be evaluated by radiologic, nuclear medicine imaging and neurophysiological examination.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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 severe ischemic changes active or chronic infection/inflammation acute or chronic hemorrhage tumor/space occupying lesion meningeal enhancement 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin Woo Chang
Organizational Affiliation
Severance Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurosurgery, Yonsei University College of Medici
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

We'll reach out to this number within 24 hrs