An interventional study of Neuronavigation-guided single-element focused ultrasound transducer and Definity in Alzheimer Disease, sponsored by Columbia University. Completed at 1 site in United States. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2024-08-26.
Sponsored by Columbia University · Not applicable, Interventional, and Device feasibility
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.
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.
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 6 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →Columbia University is the lead sponsor of 1,103 studies on the registry; 193 are open to participants now.
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Diagnosis of early Alzheimer's disease (AD) or mild cognitive impairment (MCI) at minimum. All following criteria must be met:
Exclusion Criteria:
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 · Drug: Definity · Other: Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents · Other: Positron Emission Tomography (PET) · Other: Amyvid
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.
Also known as: Perflutren Lipid Microsphere
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.
Also known as: 18F-Florbetapir
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.
Time frame: 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.
Time frame: Baseline through 3 days post-treatment
Percent Change in Amyloid PET Signal Intensity
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.
Time frame: Screening through 3 weeks post-treatment
Change in Mini-Mental State Examination (MMSE) Score
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.
Time frame: Screening through 3 months post-treatment
| Milestone | Focused Ultrasound Treatment |
|---|---|
| Started | 6 |
| Completed | 6 |
| Not completed | 0 |
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.
| Participants | Focused Ultrasound Treatment |
|---|---|
| Total Number of Individuals With Successful Opening of the BBB | 5 |
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.
| adverse events | Focused Ultrasound Treatment |
|---|---|
| Total Number of Safety Events Related to Opening of BBB | 1 |
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.
| percent change | Focused Ultrasound Treatment |
|---|---|
| Percent Change in Amyloid PET Signal Intensity | -1.47 ± 0.77 |
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.
| score on a scale | Focused Ultrasound Treatment |
|---|---|
| Change in Mini-Mental State Examination (MMSE) Score | -2.5 ± 2.93 |
Collected over Up to 5 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Focused Ultrasound Treatment | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) |
| Event | Focused Ultrasound Treatment |
|---|---|
| Mild focal edemaInjury, poisoning and procedural complications | 1/6 |
| Age, Continuous(years) | Focused Ultrasound Treatment |
|---|---|
| Mean | 69.7 ± 7.2 |
| Sex: Female, Male(Participants) | Focused Ultrasound Treatment |
|---|---|
| Female | 4 |
| Male | 2 |
| Ethnicity (NIH/OMB)(Participants) | Focused Ultrasound Treatment |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 5 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Focused Ultrasound Treatment |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 5 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| MMSE(score on a scale) | Focused Ultrasound Treatment |
|---|---|
| Mean | 18.8 ± 3.2 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No — No individual participant data (IPD) will be shared with other researchers.
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