Clinical trial NCT04526262: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Alzheimer Disease
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2020-08-25
Enrollment: 6
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Adverse events safety profile
timeFrame: 6 months
Secondary outcomes:
measure: Efficacy of BBB disruption : evaluated by radiologic imaging
timeFrame: 6 months
measure: Efficacy of BBB disruption : evaluated by nuclear medicine imaging
timeFrame: 6 months
measure: Efficacy of BBB disruption : evaluated by neurophysiological examination
timeFrame: 6 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Department of Neurosurgery, Yonsei University College of Medici
Study officials:
affiliation: Severance Hospital
name: Jin Woo Chang
role: PRINCIPAL_INVESTIGATOR
References: