Clinical trial NCT05469009: 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
Official title: Assessment of Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for the Treatment of Patients With With Mild Cognitive Impairment (MCI) or Mild Alzheimer's Disease (AD) Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Mild Cognitive Impairment
Alzheimer Disease 1
Lead sponsor: West Virginia University
Sponsor class: OTHER
Collaborators: name: InSightec
First posted: 2022-07-21
Enrollment: 15
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: DEVICE_FEASIBILITY

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 lecanemab infusion therapy, and to also evaluate the safety of the BBO procedure through patient examination (neurological and cognitive/behavioral) and MRI assessments during the treatment and follow-up.

The secondary objectives of this study is to determine the effect of BBBO in patients with MCI or mild AD treated with aducanumab or lecanemab on brain β-amyloid plaque measured by amyloid positron emission tomography (PET), as well as to assess the clinical impact of BBBO with standard aducanumab or lecanemab therapy, if any, as assessed with ADAS Cog 11 and MMSE over time following BBBO.

Eligibility criteria: 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)

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.

Primary outcomes:
measure: Treatment intervention related adverse events
timeFrame: From baseline, up to 5 year post last treatment
measure: Treatment intervention related serious adverse events
timeFrame: From baseline, up to 5 year post last treatment
Secondary outcomes:
measure: Beta-Amyloid plaques within the brain
timeFrame: From baseline, up to 5 year post last treatment
measure: Cognitive performance (ADAS COG 11)
timeFrame: From baseline, up to 5 year post last treatment
measure: Cognitive performance (MMSE)
timeFrame: From baseline, up to 5 year post last treatment
Other outcomes:
Locations:
city: Morgantown
country: United States
facility: West Virginia University Rockefeller Neuroscience Institute
state: West Virginia
Study officials:
affiliation: WVU Rockerfeller Neuroscience Institute
name: Ali Rezai, MD, FAANS
role: PRINCIPAL_INVESTIGATOR
References: