NCT05469009 · Early Phase 1 · ACTIVE NOT RECRUITING
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
This early-stage study tests whether it is safe and doable to use a focused ultrasound device, guided by MRI, to temporarily open the blood-brain barrier while people receive an approved Alzheimer's antibody infusion (lecanemab or aducanumab). The goal is to see if the combination can be done safely. It is an Early Phase 1 trial, meaning very first human testing, not proven or approved.
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.
The sponsor's own eligibility wording, lightly reformatted. The study team makes the final eligibility decision — worth discussing with your doctor.
Eligibility criteria as of 2026-01-22