Trial Outcomes & Findings for Non-invasive Blood-brain Barrier Opening in Alzheimer's Disease Patients Using Focused Ultrasound (NCT NCT04118764)

Last Updated: 2024-08-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

6 participants

Primary outcome timeframe

Baseline through 3 days post-treatment

Results posted on

2024-08-26

Participant Flow

Participant milestones

Participant milestones
Measure	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). 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: Definity microbubbles (10 μl/kg) will be used in conjunction with the ultrasound transducer to temporarily open the blood brain barrier. 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. Positron Emission Tomography (PET): A follow-up PET scan will be performed three days after treatment to determine amyloid plaque load. Amyvid: To be used during the PET scan to determine uptake of Amyvid within the treated area.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Non-invasive Blood-brain Barrier Opening in Alzheimer's Disease Patients Using Focused Ultrasound

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Focused Ultrasound Treatment n=6 Participants Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg). 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: Definity microbubbles (10 μl/kg) will be used in conjunction with the ultrasound transducer to temporarily open the blood brain barrier. 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. Positron Emission Tomography (PET): A follow-up PET scan will be performed three days after treatment to determine amyloid plaque load. Amyvid: To be used during the PET scan to determine uptake of Amyvid within the treated area.
Age, Continuous	69.7 years STANDARD_DEVIATION 7.2 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
MMSE	18.8 score on a scale STANDARD_DEVIATION 3.2 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline through 3 days post-treatment

Outcome measures

Outcome measures
Measure	Focused Ultrasound Treatment n=6 Participants Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg). 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: Definity microbubbles (10 μl/kg) will be used in conjunction with the ultrasound transducer to temporarily open the blood brain barrier. 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. Positron Emission Tomography (PET): A follow-up PET scan will be performed three days after treatment to determine amyloid plaque load. Amyvid: To be used during the PET scan to determine uptake of Amyvid within the treated area.
Total Number of Individuals With Successful Opening of the BBB	5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Focused Ultrasound Treatment n=6 Participants Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg). 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: Definity microbubbles (10 μl/kg) will be used in conjunction with the ultrasound transducer to temporarily open the blood brain barrier. 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. Positron Emission Tomography (PET): A follow-up PET scan will be performed three days after treatment to determine amyloid plaque load. Amyvid: To be used during the PET scan to determine uptake of Amyvid within the treated area.
Total Number of Safety Events Related to Opening of BBB	1 adverse events

SECONDARY outcome

Timeframe: Screening through 3 weeks 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.

Outcome measures

Outcome measures
Measure	Focused Ultrasound Treatment n=6 Participants Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg). 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: Definity microbubbles (10 μl/kg) will be used in conjunction with the ultrasound transducer to temporarily open the blood brain barrier. 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. Positron Emission Tomography (PET): A follow-up PET scan will be performed three days after treatment to determine amyloid plaque load. Amyvid: To be used during the PET scan to determine uptake of Amyvid within the treated area.
Percent Change in Amyloid PET Signal Intensity	-1.47 percent change Standard Deviation 0.77

SECONDARY outcome

Timeframe: Screening through 3 months post-treatment

The MMSE is a questionnaire that is used to measure cognitive impairment. The total score range is 0 to 30, with a higher score indicating a better outcome. Cognitive function will be assessed before and after the focused ultrasound treatment to determine the change in MMSE.

Outcome measures

Outcome measures
Measure	Focused Ultrasound Treatment n=6 Participants Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg). 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: Definity microbubbles (10 μl/kg) will be used in conjunction with the ultrasound transducer to temporarily open the blood brain barrier. 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. Positron Emission Tomography (PET): A follow-up PET scan will be performed three days after treatment to determine amyloid plaque load. Amyvid: To be used during the PET scan to determine uptake of Amyvid within the treated area.
Change in Mini-Mental State Examination (MMSE) Score	-2.5 score on a scale Standard Deviation 2.93

Adverse Events

Focused Ultrasound Treatment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Focused Ultrasound Treatment n=6 participants at risk Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with Definity Microbubbles (10 μl/kg). 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: Definity microbubbles (10 μl/kg) will be used in conjunction with the ultrasound transducer to temporarily open the blood brain barrier. 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. Positron Emission Tomography (PET): A follow-up PET scan will be performed three days after treatment to determine amyloid plaque load. Amyvid: To be used during the PET scan to determine uptake of Amyvid within the treated area.
Injury, poisoning and procedural complications Mild focal edema	16.7% 1/6 • Number of events 1 • Up to 5 months

Additional Information

Elisa Konofagou, PhD, Robert and Margaret Hariri Professor in Biomedical Engineering and Radiology

Columbia University

Phone: 212-342-0863

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place