Neuronavigation-guided FUS-induced BBB Opening in Alzheimer's Disease Patients and Its Effects on Brain Amyloid and Tau
- Conditions
- Alzheimer Disease, Early Onset
- Interventions
- Device: Neuronavigation-guided single-element focused ultrasound transducerOther: Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agentsRadiation: Positron Emission Tomography (PET)Diagnostic Test: Blood drawDevice: UR5eDiagnostic Test: Urine test
- Registration Number
- NCT06600880
- Lead Sponsor
- Columbia University
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 6
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Focused ultrasound treatment Neuronavigation-guided single-element focused ultrasound transducer Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. Focused ultrasound treatment Lumason Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. Focused ultrasound treatment Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. Focused ultrasound treatment Positron Emission Tomography (PET) Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. Focused ultrasound treatment Amyvid Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. Focused ultrasound treatment MK-6240 Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. Focused ultrasound treatment Dotarem Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. Focused ultrasound treatment Blood draw Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. Focused ultrasound treatment UR5e Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles. Focused ultrasound treatment Urine test Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.
- Primary Outcome Measures
Name Time Method Total Number of Individuals With Successful Opening of the BBB 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 Outcome Measures
Name Time Method Total Number of Safety Events Related to Opening of BBB 4 days, including the day of treatment Showing safe BBB opening for all patients without any Adverse Event nor Serious Adverse Event, and showing its safety as well in 3 days after treatment
Percent Change in Amyloid PET Signal Intensity 3 months (±2 weeks) A moderately shown in our previous clinical trial study, we expect to observe a slowed down increase of Amyloid protein load after the treatment on the two follow-ups performed at 3 weeks (±1 week) and 3 months (±2 week) after treatment.
Percent Change in MK-6240 PET Signal Intensity 3 months (±2 weeks) As shown in our previous studies in mice, we expect to observe a slowed down increase or reduction on Tau protein load after the treatment on the two follow-ups performed at 3 weeks (±1 week) and 3 months (±2 week) after treatment.
Trial Locations
- Locations (1)
Columbia University Irving Medical Center
🇺🇸New York, New York, United States