Neuronavigation-guided Focused Ultrasound-induced Blood-brain Barrier Opening in Alzheimer's Disease Patients and Its Effects on Brain Amyloid and Tau
Overview
- Phase
- Phase 1
- Intervention
- Neuronavigation-guided single-element focused ultrasound transducer
- Conditions
- Alzheimer Disease, Early Onset
- Sponsor
- Columbia University
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Total Number of Individuals With Successful Opening of the BBB
- Status
- Not Yet Recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
The primary purpose of this phase 1b study is to further assess the safety and reversibility of focused ultrasound induced blood-brain barrier opening (FUS-BBBO) in participants with Alzheimer´s Disease (AD) using a single-element transducer with neuronavigation guidance. Preliminary results from our phase 1a study demonstrate that our neuronavigation-guided FUS system was capable of safely and transiently open the BBB in participants with AD. The information collected in this new study may be used to design future clinical trials to ultimately provide a viable alternative for treatment of AD in a safe and noninvasive manner.
Our secondary objective includes the assessment of the therapeutic efficacy of FUS-BBBO in reducing amyloid beta and neurofibrillary tangles, the main hallmark pathologies of AD, using PET tracers. Based on our preclinical studies in AD transgenic mouse models, FUS-BBBO alone was able to reduce both the amyloid beta and tau protein load, resulting in improvements in behavioral tasks assessing memory. Therefore, in this new study, the effect of FUS-BBBO on the amyloid beta and tau protein load in patients with AD will be assessed through the use of PET tracers.
Detailed Description
Regarding the primary purpose of this study, the human module for the neuronavigator was implemented in our phase 1a trial, and initial feasibility and safety in a small cohort of AD patients had been tested, with a fast procedural time that required no anesthesia. Regarding the secondary objective, both amyloid beta and tau protein load in the brain will be assessed at baseline (before FUS-BBBO treatment), and 3-weeks and 3-months after FUS-BBBO treatment, to assess any short-term or long-term changes, respectively.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
Intervention: Neuronavigation-guided single-element focused ultrasound transducer
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
Intervention: Lumason
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
Intervention: Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
Intervention: Positron Emission Tomography (PET)
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
Intervention: Amyvid
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
Intervention: MK-6240
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
Intervention: Dotarem
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
Intervention: Blood draw
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
Intervention: UR5e
Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
Intervention: Urine test
Outcomes
Primary Outcomes
Total Number of Individuals With Successful Opening of the BBB
Time Frame: 4 days, including the day of treatment
Opening the BBB successfully in all the patients, while obtaining a volume of BBB opened being similar and consistent for all patients
Secondary Outcomes
- Total Number of Safety Events Related to Opening of BBB(4 days, including the day of treatment)
- Percent Change in Amyloid PET Signal Intensity(3 months (±2 weeks))
- Percent Change in MK-6240 PET Signal Intensity(3 months (±2 weeks))