Repetitive Blood Brain Barrier Opening for Alzheimer's Disease.

NCT06158789 | Unknown

• 1 other identifier: YUSHAD-02
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (4)

• Changes in Standard Uptake Value Ratios (SUVR) on FBB-PET

  Conducting FBB (18F-Florbetaben)-PET scans to confirm the presence of Amyloid beta protein (Aβ) plaques in the brain, the study compares and analyzes the global and regional standard uptake value ratios (SUVR) before the first procedure (Visit 1) and after the third procedure (Visit 12). The cerebellar gray matter is used as a reference region, and the analysis includes whole-brain as well as regional (Frontal/Temporal) SUVR.

  Screening, 2weeks after final procedure

• Changes in CGA-NPI (Caregiver-administered neuropsychiatric inventory) Scores and Percentage Change

  To assess the cognitive function of participants, the CGA-NPI (Caregiver-Administered Neuropsychiatric Inventory) test is administered before the first procedure (Visit 1) and compared to scores after the first, second, and third procedures (Visits 4, 8, 12, 13). Changes in CGA-NPI scores and percentage changes (%) are investigated at each assessment point, with responses provided by the same participant's caregiver. Higher scores indicate severity of neuropsychiatric symptoms and 0 indicates no symptom.

  Screening, 2weeks after every session, 2months after final session

• Changes in K-MMSE(Korean version of Mini Mental State Exam) Test Scores and Percentage Change

  For evaluating cognitive function, the K-MMSE (Korean version of Mini Mental State Exam) test is conducted before the first procedure (Visit 1) and compared to scores after the third procedure (Visits 12, 13). Changes in K-MMSE scores and percentage changes (%) are examined. Higher scores indicate better cognition.

  Screening, 2months after final session

• Changes in SNSB(Seoul Neuropsychological Screening Battery)Test Scores and Percentage Change

  Assessing cognitive function, the SNSB (Seoul Neuropsychological Screening Battery) test is performed before the first procedure (Visit 1) and compared to scores after the third procedure (Visit 13). Changes in SNSB scores and percentage changes (%) are investigated. Higher scores indicate better cognition.

  Screening, 2months after final session

Study Arms (1)

Focused ultrasound treatment group

EXPERIMENTAL

Procedure: MR guided low intensity focused ultrasound

Interventions

MR guided low intensity focused ultrasound PROCEDURE

Low intensity focused ultrasound opens the blood brain barrier

Focused ultrasound treatment group

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Kyung Won Chang: lead
• Yonsei University: collaborator

Study Sites (1)

Yonsei University Severance Hospital

Seoul, 03722, South Korea

Location

Related Publications (1)

• 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.

  PMID: 34740367 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Jin Woo Chang, MD,PhD

  Yonsei University

  PRINCIPAL INVESTIGATOR

• Byoung Seok Ye, MD,PhD

  Yonsei University

  STUDY CHAIR

• Kyung Won Chang, MD

  Yonsei University

  STUDY DIRECTOR

• Kyung Won Chang, MD,PhD

  Yonsei University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical professor

Study Record Dates

• First Submitted: November 20, 2023
• First Posted: December 6, 2023
• Study Start: June 2, 2022
• Primary Completion: July 19, 2023
• Study Completion: January 19, 2024
• Last Updated: December 6, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)