NCT04118764

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

Completed NA Results posted Last updated 26 August 2024

What this trial tests

NA trial testing Neuronavigation-guided single-element focused ultrasound transducer in Alzheimer Disease in 6 participants. Completed in 28 September 2022.

Timeline

6 August 2020

Primary endpoint
11 July 2022

28 September 2022

Quick facts

Lead sponsor	Columbia University
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	device feasibility
Enrollment	6
Start date	6 August 2020
Primary completion	11 July 2022
Estimated completion	28 September 2022
Sites	1 location across United States

Drugs / interventions tested

• Neuronavigation-guided single-element focused ultrasound transducer
• Definity — full drug profile →
• Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents
• Positron Emission Tomography (PET) — full drug profile →
• Amyvid (FLORBETAPIR) — full drug profile →

Conditions studied

• Alzheimer Disease — all drugs for Alzheimer Disease →

Sponsor

Columbia University

Who can join

50 and older, any sex, with Alzheimer Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Total Number of Individuals With Successful Opening of the BBB Primary · 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.

Group	Value	95% CI
Focused Ultrasound Treatment	5

Total Number of Safety Events Related to Opening of BBB Primary · 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.

Group	Value	95% CI
Focused Ultrasound Treatment	1

Percent Change in Amyloid PET Signal Intensity Secondary · 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.

Group	Value	95% CI
Focused Ultrasound Treatment	-1.47	± 0.77

Change in Mini-Mental State Examination (MMSE) Score Secondary · 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.

Group	Value	95% CI
Focused Ultrasound Treatment	-2.5	± 2.93

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 5 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Focused Ultrasound Treatment

Serious: 0/6 (0%)

Deaths: 0/6

Other adverse events (1 terms — click to expand)

Reaction	System	Focused Ultrasound Treatment
Mild focal edema	Injury, poisoning and procedural complications	—

Data from ClinicalTrials.gov NCT04118764 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current Strategies to Enhance Delivery of Drugs across the Blood-Brain Barrier.
   Teleanu RI, Preda MD, Niculescu AG, Vladâcenco O, et al · · 2022 · cited 122× · PMID 35631573 · DOI 10.3390/pharmaceutics14050987
2. Development of Novel Therapeutics Targeting the Blood-Brain Barrier: From Barrier to Carrier.
   Li J, Zheng M, Shimoni O, Banks WA, et al · · 2021 · cited 121× · PMID 34085418 · DOI 10.1002/advs.202101090
3. Applications of focused ultrasound-mediated blood-brain barrier opening.
   Gorick CM, Breza VR, Nowak KM, Cheng VWT, et al · · 2022 · cited 95× · PMID 36272635 · DOI 10.1016/j.addr.2022.114583
4. Cavitation-modulated inflammatory response following focused ultrasound blood-brain barrier opening.
   Ji R, Karakatsani ME, Burgess M, Smith M, et al · · 2021 · cited 88× · PMID 34324895 · DOI 10.1016/j.jconrel.2021.07.042
5. Safety evaluation of a clinical focused ultrasound system for neuronavigation guided blood-brain barrier opening in non-human primates.
   Pouliopoulos AN, Kwon N, Jensen G, Meaney A, et al · · 2021 · cited 76× · PMID 34294761 · DOI 10.1038/s41598-021-94188-3
6. Extensive frontal focused ultrasound mediated blood-brain barrier opening for the treatment of Alzheimer's disease: a proof-of-concept study.
   Park SH, Baik K, Jeon S, Chang WS, et al · · 2021 · cited 74× · PMID 34740367 · DOI 10.1186/s40035-021-00269-8
7. Therapeutic Agent Delivery Across the Blood-Brain Barrier Using Focused Ultrasound.
   McMahon D, O'Reilly MA, Hynynen K. · · 2021 · cited 67× · PMID 33752471 · DOI 10.1146/annurev-bioeng-062117-121238
8. Ultrasound-Mediated Blood-Brain Barrier Disruption for Drug Delivery: A Systematic Review of Protocols, Efficacy, and Safety Outcomes from Preclinical and Clinical Studies.
   Gandhi K, Barzegar-Fallah A, Banstola A, Rizwan SB, et al · · 2022 · cited 62× · PMID 35456667 · DOI 10.3390/pharmaceutics14040833