Neuronavigation-guided FUS-induced BBB Opening in Alzheimer's Disease Patients and Its Effects on Brain Amyloid and Tau

Launched by COLUMBIA UNIVERSITY · Sep 13, 2024

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment approach for patients with Alzheimer’s Disease (AD) using a method called focused ultrasound (FUS). The main goal is to safely open the blood-brain barrier (BBB), which is a protective shield around the brain that can make it difficult for medications to reach brain tissue. By using a special device that guides the ultrasound, researchers hope to see if this method can help reduce harmful proteins in the brain, known as amyloid beta and tau, which are linked to Alzheimer's. The trial will also collect important safety information to help design future studies.

To participate in this trial, individuals must be over 50 years old and have a diagnosis of mild cognitive impairment (MCI) or Alzheimer's Disease. They will need to pass some assessments that measure their memory and overall health. Participants can expect to undergo initial screenings, including MRI scans, to ensure they are suitable for the study. This trial is not yet recruiting, but it represents an exciting step toward potentially safer and non-invasive treatment options for Alzheimer’s patients.

Gender

ALL

Eligibility criteria

• Inclusion Criteria. AD patients will be recruited in person and have to be over 50 years of age and able to give consent. Patients diagnosed with MCI or AD will be included in our study. Other more severe symptomatic patients will be eligible to enroll, as long as they have the ability to consent for their participation. Screening is essential and will be performed by our collaborator and neurologist of the study, Dr. Lawrence Honig, MD at the Taub Institute of Alzheimer's Disease and Aging at Columbia. After the initial screening we will acquire MRI scans as part of the study and finalize enrollment or exclusion of the patient. Inclusion criteria thus include:
• • Age greater than 50 years old.
• * Diagnosis of MCI or AD. All following criteria must be met:
• • MMSE score between 12 and 26.
• • Modified Hachinski Ischemia Scale (MHIS) score of \<= 4
• • Short form Geriatric Depression Scale (GDS) score of \<= 6.
• • PET scan confirming amyloid plaque load using Amyvid (18F-Florbetapir).
• • PET scan confirming tau positivity in the frontal lobe using MK-6240 (F18-Florquinitau).
• • Ability to provide informed consent.
• Exclusion Criteria. Exclusion criteria include surgeries and other pathologies not associated with AD, as outlined in the following list:
• • Prior administration of any amyloid-reducing agent such as aducanumab or lecanemab.
• • Contraindication for MRI.
• • Contra-indication history or hypersensitivity to MRI contrast agents (e.g., Dotarem) or microbubbles (e.g., Definity, Lumason), including polyethylene glycol (PEG) allergy.
• • Prior brain surgery, including deep brain stimulation.
• • Metallic implants.
• • Abnormal coagulation profile (significant abnormality in PT, PTT, or platelets).
• • Anticoagulant therapy.
• • History of seizure disorder.
• • Brain atrophy to a degree that would interfere with ultrasound delivery.
• • Inability to comply with the procedures of the protocol, including follow-up scans.
• • Women with capacity to bear children or lactating.
• • Impaired renal function with estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2 provided by a standard blood test 2-4 weeks prior to the ultrasound treatment.
• • Active infection/inflammation.
• • Acute or chronic hemorrhages, i.e. \> 4 lobar microbleeds, or an area of siderosis or macrohemorrhages.
• • Tumors or space-occupying lesions of significance.
• • Any uncontrolled medical disorder that might interfere with the ability to safely perform the study.