Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer's Disease Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy

Early Phase 1

Recruiting

• Conditions: Mild Cognitive Impairment; Alzheimer Disease 1
• Interventions: Drug: Aducanumab; Device: Exablate Model 4000 Type 2; Drug: Lecanemab

• Registration Number: NCT05469009
• Lead Sponsor: Ali Rezai

Brief Summary

The purpose of this study is to assess the safety and feasibility of administering standard of care monoclonal antibody (mAb) infusion therapy in combination with opening the blood-brain barrier with the Exablate Model 4000 Type 2 device in patients with mild Alzheimer's disease (AD) or mild cognitive impairment (MCI).

Detailed Description

The primary objectives of this study is to evaluate the safety and feasibility of BBBO (blood-brain barrier opening) using the Exablate Model 4000 Type 2 in the setting of standard aducanumab or lecanemab therapy among patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD) with confirmed β-amyloid, who are eligible for aducanumab or l...

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2022-07-14
• Study First Submitted: 2022-07-19
• Study First Submitted QC: 2022-07-19
• Study First Posted: 2022-07-21
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-16
• Last Update Posted: 2024-02-20
• Primary Completion: 2029-07
• Study Completion: 2029-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Able and willing to give informed consent
• Probable mild cognitive impairment due to AD
• Modified Hachinski Ischemia Scale (MHIS) score of <= 4
• Mini Mental State Exam (MMSE) scores > 21+.
• Short form Geriatric Depression Scale (GDS) score of <= 7
• Amyloid PET scan consistent with the presence of β-amyloid (A+)
• Able to communicate sensations during the Exablate MRgFUS procedure
• Able to attend all study visits (i.e., life expectancy of 1 year or more)

Read More

Exclusion Criteria

• MRI findings:
• Significant cardiac disease or unstable hemodynamic status
• History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage
• Known cerebral or systemic vasculopathy
• Significant depression (GDS > 7) and/or at potential risk of suicide (C-SSRS > 2)
• A severity score of 2 or more on any of the 'Delusions', 'Hallucinations' or 'Agitation/Aggression' subscales of the Neuropsychiatry Inventory (NPI-Q)
• Known sensitivity/allergy to gadolinium(gadobutrol), DEFINITY or its components, or 18F-florbetaben.
• Known hypersensitivity to DEFINITY or its components.
• Any contraindications to MRI scanning
• Untreated, uncontrolled sleep apnea
• History of untreated or uncontrolled seizure disorder or epilepsy.
• Impaired renal function
• Does not have a reliable caregiver
• Currently in a clinical trial involving an investigational product or non-approved use of a drug or device or in any other type of medical research.
• Respiratory: chronic pulmonary disorders
• History of clinically significant recent drug or alcohol use disorder who may be at higher risk for seizure or infection.
• Positive human immunodeficiency virus (HIV) which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis.
• Potential blood-borne infections, which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Infusion plus Exablate BBBO Treatment	Exablate Model 4000 Type 2	Intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS.
Infusion plus Exablate BBBO Treatment	Aducanumab	Intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS.
Infusion plus Exablate BBBO Treatment	Lecanemab	Intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS.

Primary Outcome Measures

Name	Time	Method
Treatment intervention related adverse events	From baseline, up to 5 year post last treatment	The total number of adverse events following each treatment through end of the study
Treatment intervention related serious adverse events	From baseline, up to 5 year post last treatment	The total number of serious adverse events following each treatment through end of the study

Secondary Outcome Measures

Name	Time	Method
Cognitive performance (MMSE)	From baseline, up to 5 year post last treatment	Change in cognitive performance using the Mini Mental Status Exam, rating scores from 0-30. 25 or higher being classed as normal. A score below 24 is considered abnormal, indicating possible cognitive impairment.
Cognitive performance (ADAS COG 11)	From baseline, up to 5 year post last treatment	Change in cognitive performance using the Alzheimer's Disease Assessment Cognitive Subscale, rating scores from 0-70. The greater the dysfunction, the greater the score. A score of 70 represents the most severe impairment and 0 represents the least impairment.
Beta-Amyloid plaques within the brain	From baseline, up to 5 year post last treatment	Beta-Amyloid uptake value measured by Amyloid PET scan

Trial Locations

Locations (1)

West Virginia University Rockefeller Neuroscience Institute; 🇺🇸 Morgantown, West Virginia, United States