Non-invasive Blood-brain Barrier Opening in Alzheimer's Disease Patients Using Focused Ultrasound
Neuronavigation-guided Focused Ultrasound-induced Blood-brain Barrier Opening in Alzheimer's Disease Patients
2 other identifiers
interventional
6
1 country
1
Brief Summary
The purpose of this study is to test a new technique that may, in the future, help deliver medications to the brain of people with Alzheimer's disease. Participants in this study will undergo a focused ultrasound treatment to the brain, along with Magnetic Resonance Imagine (MRI) and Positron Emission Tomography (PET) scans.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable alzheimer-disease
Started Aug 2020
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 1, 2019
CompletedFirst Posted
Study publicly available on registry
October 8, 2019
CompletedStudy Start
First participant enrolled
August 6, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 11, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
September 28, 2022
CompletedResults Posted
Study results publicly available
August 26, 2024
CompletedAugust 26, 2024
July 1, 2024
1.9 years
October 1, 2019
May 22, 2024
July 31, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Total Number of Individuals With Successful Opening of the BBB
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.
Baseline through 3 days post-treatment
Total Number of Safety Events Related to Opening of BBB
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.
Baseline through 3 days post-treatment
Secondary Outcomes (2)
Percent Change in Amyloid PET Signal Intensity
Screening through 3 weeks post-treatment
Change in Mini-Mental State Examination (MMSE) Score
Screening through 3 months post-treatment
Study Arms (1)
Focused ultrasound treatment
EXPERIMENTALNeuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg).
Interventions
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.
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.
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.
Eligibility Criteria
You may qualify if:
- years of age or older.
- Diagnosis of early Alzheimer's disease (AD) or mild cognitive impairment (MCI) at minimum. All following criteria must be met:
- Probable MCI or AD consistent with criteria outlined in (McKhann et al 2011, Petersen et al 2018).
- Mini Mental State Examination (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).
- Ability to provide informed consent.
You may not qualify if:
- Contraindication for Magnetic Resonance Imaging (MRI).
- Contra-indication history or hypersensitivity to MRI contrast agents (e.g., Dotarem) or microbubbles (e.g., Definity).
- Prior brain surgery, including deep brain stimulation.
- Metallic implants.
- Moderate or severe uncontrolled hypertension (systolic blood pressure \> 140 mmHg).
- Abnormal coagulation profile, e.g. hemophilia A or B.
- Coagulopathy or under anticoagulant therapy.
- History of stroke or cardiovascular disease.
- Active/detectable gingivitis, herpes simplex, hepatitis, tuberculosis, and minor skin or respiratory infections.
- History of seizure disorder.
- History of asthma or allergies to food or medication with significant symptoms in past 3 years.
- Severe brain atrophy.
- Inability to comply with the procedures of the protocol, including follow-up MRI scans.
- Pregnancy or lactation.
- Impaired renal function with estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2 provided by a standard blood test at maximum 2 weeks prior to the ultrasound treatment.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Columbia Universitylead
- National Institute on Aging (NIA)collaborator
Study Sites (1)
Columbia University Irving Medical Center/NYPH
New York, New York, 11021, United States
Related Publications (4)
Wu SY, Aurup C, Sanchez CS, Grondin J, Zheng W, Kamimura H, Ferrera VP, Konofagou EE. Efficient Blood-Brain Barrier Opening in Primates with Neuronavigation-Guided Ultrasound and Real-Time Acoustic Mapping. Sci Rep. 2018 May 22;8(1):7978. doi: 10.1038/s41598-018-25904-9.
PMID: 29789530BACKGROUNDPouliopoulos AN, Wu SY, Burgess MT, Karakatsani ME, Kamimura HAS, Konofagou EE. A Clinical System for Non-invasive Blood-Brain Barrier Opening Using a Neuronavigation-Guided Single-Element Focused Ultrasound Transducer. Ultrasound Med Biol. 2020 Jan;46(1):73-89. doi: 10.1016/j.ultrasmedbio.2019.09.010. Epub 2019 Oct 25.
PMID: 31668690BACKGROUNDKarakatsani ME, Ji R, Murillo MF, Kugelman T, Kwon N, Lao YH, Liu K, Pouliopoulos AN, Honig LS, Duff KE, Konofagou EE. Focused ultrasound mitigates pathology and improves spatial memory in Alzheimer's mice and patients. Theranostics. 2023 Jul 14;13(12):4102-4120. doi: 10.7150/thno.79898. eCollection 2023.
PMID: 37554284DERIVEDMathew AS, Gorick CM, Price RJ. Multiple regression analysis of a comprehensive transcriptomic data assembly elucidates mechanically- and biochemically-driven responses to focused ultrasound blood-brain barrier disruption. Theranostics. 2021 Oct 11;11(20):9847-9858. doi: 10.7150/thno.65064. eCollection 2021.
PMID: 34815790DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Elisa Konofagou, PhD, Robert and Margaret Hariri Professor in Biomedical Engineering and Radiology
- Organization
- Columbia University
Study Officials
- PRINCIPAL INVESTIGATOR
Elisa Konofagou, PhD
Columbia University
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- DEVICE FEASIBILITY
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 1, 2019
First Posted
October 8, 2019
Study Start
August 6, 2020
Primary Completion
July 11, 2022
Study Completion
September 28, 2022
Last Updated
August 26, 2024
Results First Posted
August 26, 2024
Record last verified: 2024-07
Data Sharing
- IPD Sharing
- Will not share
No individual participant data (IPD) will be shared with other researchers.