Non-invasive Blood-brain Barrier Opening in Alzheimer's Disease Patients Using Focused Ultrasound
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04118764|
Recruitment Status : Recruiting
First Posted : October 8, 2019
Last Update Posted : October 29, 2021
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease||Device: Neuronavigation-guided single-element focused ultrasound transducer Drug: Definity Other: Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents Other: Positron Emission Tomography (PET) Other: Amyvid||Not Applicable|
Central nervous system disorders are currently being symptomatically treated since the molecular events provoking their onset have not been yet identified. Drug delivery techniques have to overcome the almost impermeable blood-brain barrier (BBB) and can be grouped into two main categories: (i) invasive and targeted, and (ii) non-invasive and non-targeted methods. However, the technological advances of the past decades revealed the immense potential of focused ultrasound (FUS) in transcranial applications. In contrast to other techniques, FUS-mediated BBB opening is both non-invasive and targeted. The localized energy delivery coupled with the circulation of intravenously administered microbubbles initiates biological effects confined only to the vessel walls and contained only in the targeted region within the brain.
The purpose of the study is to assess the safety and feasibility of focused ultrasound-induced blood-brain barrier opening in Alzheimer's disease patients, using a single-element transducer with neuronavigation guidance. The investigators will also test whether treatment with focused ultrasound alone alters the amyloid protein levels in the treated brain areas and its potential effects on the cognitive function of Alzheimer's patients.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Device Feasibility|
|Official Title:||Neuronavigation-guided Focused Ultrasound-induced Blood-brain Barrier Opening in Alzheimer's Disease Patients|
|Actual Study Start Date :||October 1, 2020|
|Estimated Primary Completion Date :||July 2022|
|Estimated Study Completion Date :||July 2022|
Experimental: Focused ultrasound treatment
Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg).
Device: Neuronavigation-guided single-element focused ultrasound transducer
Non-invasive focused ultrasound-induced blood-brain barrier opening will be attempted using a single-element transducer, guided with a neuronavigation system.
Definity microbubbles (10 μl/kg) will be used in conjunction with the ultrasound transducer to temporarily open the blood brain barrier.
Other Name: Perflutren Lipid Microsphere
Other: Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents
MRI scans will be completed at baseline and immediately after the focused ultrasound treatment to confirm BBB opening and safety. A follow-up MRI will be performed three days after treatment to confirm BBB closure, only in the case of successful BBB opening.
Other: Positron Emission Tomography (PET)
A follow-up PET scan will be performed three days after treatment to determine amyloid plaque load.
To be used during the PET scan to determine uptake of Amyvid within the treated area.
Other Name: 18F-Florbetapir
- Total Number of Individuals with Successful Opening of the BBB [ Time Frame: Baseline through 3 days post-treatment ]The total number of individuals with successful opening of the BBB will be assessed. Blood-brain barrier opening volume will be measured in mm^3 through contrast-enhanced T1-weighted MRI on the day of the focused ultrasound treatment and 3 days after treatment, to confirm blood-brain barrier restoration.
- Total number of Safety Events Related to Opening of BBB [ Time Frame: Baseline through 3 days post-treatment ]The total number of safety events related to opening of the BBB as assessed by T2 and susceptibility-weighted (SWI) MRI. Safety will be established by the presence and the total area of hyper-intense or hypo-intense areas in the T2 and SWI scans.
- Percent Change in Amyloid PET Signal Intensity [ Time Frame: Screening through 3 days post-treatment ]Amyloid plaques will be assessed through PET imaging before and after the focused ultrasound treatment. The standardized uptake value ratio images (SUVr) will be compared before and after the FUS treatment, to investigate if there is a change in the uptake of 18F-Florbetapir within the treated area.
- Change in Mini-Mental State Examination (MMSE) Score [ Time Frame: Screening through 3 months post-treatment ]The MMSE is a 30-point questionnaire that is used to measure cognitive impairment. MMSE scores range from 0 (worst outcome)-30 (better outcome). Cognitive function will be assessed before and after the focused ultrasound treatment to determine a the change in MMSE.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04118764
|Contact: Elisa Konofagou, PhD||(212) firstname.lastname@example.org|
|Contact: Katherine Liu, MS||(212) email@example.com|
|United States, New York|
|Columbia University Irving Medical Center/NYPH||Recruiting|
|New York, New York, United States, 11021|
|Contact: Elisa Konofagou, PhD 212-342-1612 firstname.lastname@example.org|
|Contact: Katherine Liu, MS (212) 342-1612 email@example.com|
|Principal Investigator: Elisa Konofagou, PhD|
|Sub-Investigator: Lawrence S. Honig, MD, PhD|
|Principal Investigator:||Elisa Konofagou, PhD||Columbia University|