Clinical trial NCT06158789: Repetitive Blood Brain Barrier Opening for Alzheimer's Disease.
Official title: Single-center, Open, Prospective, Single-arm, Feasibility, Investigator-initiated Trial for Assessment of Efficacy and Safety of Repetitive Blood Brain Barrier Disruption Using High Intensity Focused Ultrasound 'ExAblate 4000 Type 2' in Patients With Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Lead sponsor: Severance Hospital
Sponsor class: OTHER
Collaborators: name: Yonsei University
First posted: 2023-12-06
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: This study was focused on comparing the efficacy of repetitive Focused ultrasound mediated BBB opening in alzhemer's disease in increased number of treatment session and shorter intervals.


Eligibility criteria: Inclusion Criteria:

* Age over 50 to 85
* MMSE below 23
* FBB-PET positive
* FDG-PET shows alzheimer -induced neurodegeneration
* Dementia or cognitive impairment due to alzhemer's disease
* participants who have taken over 3 months of medication related with cognitive improvement
* Someone who can express their sensations during the procedure.
* Individuals who have voluntarily decided to participate in this clinical trial and have provided written consent on the informed consent form.
* Individuals with a commitment to adhere to the clinical trial protocol.

Exclusion Criteria:

* If any of the following exclusion criteria apply, participation in this clinical trial is not allowed.

If the severity score for the items "Delusions," "Hallucinations," or "Agitation/Aggression" in the CGA-NPI (Caregiver-Administrated Neuropsychiatry Inventory) test is greater than 2.

Note: Since the CGA-NPI requires the patient's caregiver to complete the survey, the caregiver must be present during the questionnaire.

Individuals with sensitivity/allergy or contraindications to the MRI contrast agents Gadolinium (Gadovist®) or ultrasound contrast agent Definity.

Contraindications:

Gadolinium (Gadovist®): Patients with untreated hypokalemia. Definity: Patients who have undergone right-left shunt, bidirectional shunt, or temporary right-left shunt, patients scheduled to undergo extracorporeal shock wave lithotripsy within 24 hours, clinically unstable or worsening congestive heart failure patients, acute myocardial infarction or acute coronary syndrome patients, patients at high risk of arrhythmias due to severe ventricular arrhythmias or prolongation of the QT interval, patients showing signs and symptoms of carbon dioxide retention or hypoxemia, patients with conditions that may induce pulmonary artery hypertension due to severe pulmonary insufficiency, severe pulmonary fibrosis, or damage to the pulmonary artery structure.

Individuals with standard contraindications to MR imaging, including the presence of metal devices incompatible with MRI.

Individuals with sensitivity/allergy or contraindications to anesthetic agents used for conscious sedation during procedures where conscious sedation is required.

Individuals with any of the following findings in the MRI examination:

Severe ischemic changes (Fazeka criteria score \> 2, Lacunes count \> 5, or Cerebral microbleeds count \> 3).

Active or chronic infection/inflammation. Acute or chronic bleeding. Tumor/space-occupying lesion. Meningeal enhancement. Intracranial hypotension.

Individuals with more than 30% of the skull area through which the sonication (Sonication) path passes covered with scars, scalp disorders (e.g., eczema), or atrophied scalp.

Individuals with a history of seizure disorder or epilepsy that could be exacerbated due to blood-brain barrier opening.

Individuals with a history of bleeding disorders.

Individuals with severe cardiac conditions or unstable hemodynamic status (e.g., uncontrollable hypertension, arrhythmias, angina, etc.).

Individuals with impaired kidney function (Glomerular filtration rate \< 30 mL/min/1.73 m²).

Individuals with severe brain atrophy to an extent that cannot be targeted.

Individuals who are HIV (Human Immunodeficiency Virus) positive and have a high likelihood of developing HIV encephalitis as HIV enters the brain parenchyma.

Individuals with potential vascular-origin infections that can enter the brain parenchyma, leading to meningitis or brain abscess.

Individuals with a thin blood-brain barrier, known to have homozygosity of the Apolipoprotein E allele (ApoE4).

Pregnant or lactating women.

For fertile women\*, those who have agreed to use clinically appropriate contraceptive methods\*\* during the trial period.

Definition of fertile women: Women who have experienced menarche and are not defined as postmenopausal after 12 months of amenorrhea without any surgical infertility procedures (e.g., hysterectomy or bilateral oophorectomy).

\*\* Clinically appropriate contraceptive methods: For women, it is defined as "\[Intrauterine device (e.g., loop, Mirena), chemical contraception (birth control pills), or subcutaneous contraceptive devices (e.g., Implanon)\] + Physical contraceptive methods (male or female)," and for tubal ligation or laparoscopic contraception (a type of tubal ligation).

Individuals currently participating in another clinical trial or who have participated in another clinical trial within 90 days of the screening date.

Other cases where the investigator deems participation in the clinical trial inappropriate due to ethical or potential impact on clinical trial results.

Specific reasons should be documented in the case record.

Primary outcomes:
measure: Changes in Standard Uptake Value Ratios (SUVR) on FBB-PET
timeFrame: Screening, 2weeks after final procedure
measure: Changes in CGA-NPI (Caregiver-administered neuropsychiatric inventory) Scores and Percentage Change
timeFrame: Screening, 2weeks after every session, 2months after final session
measure: Changes in K-MMSE(Korean version of Mini Mental State Exam) Test Scores and Percentage Change
timeFrame: Screening, 2months after final session
measure: Changes in SNSB(Seoul Neuropsychological Screening Battery)Test Scores and Percentage Change
timeFrame: Screening, 2months after final session
Secondary outcomes:
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Yonsei University Severance Hospital
Study officials:
affiliation: Yonsei University
name: Jin Woo Chang, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yonsei University
name: Byoung Seok Ye, MD,PhD
role: STUDY_CHAIR
affiliation: Yonsei University
name: Kyung Won Chang, MD
role: STUDY_DIRECTOR
affiliation: Yonsei University
name: Kyung Won Chang, MD,PhD
role: STUDY_DIRECTOR
References:
citation: Park SH, Baik K, Jeon S, Chang WS, Ye BS, Chang JW. Extensive frontal focused ultrasound mediated blood-brain barrier opening for the treatment of Alzheimer's disease: a proof-of-concept study. Transl Neurodegener. 2021 Nov 5;10(1):44. doi: 10.1186/s40035-021-00269-8.