Focused Ultrasound for Alzheimer's Disease

(FUS-AD Trial)

Overseen By Sergio Jimenez Gambin, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Columbia University

Must not be taking: Amyloid-reducing agents, Anticoagulants

Disqualifiers: Seizure disorder, Brain atrophy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating Alzheimer's Disease (AD) by using focused ultrasound to temporarily open the blood-brain barrier, a protective layer around the brain, to assess its safety and effectiveness. Researchers aim to reduce harmful proteins linked to Alzheimer’s, potentially improving memory and behavior. The trial is suitable for individuals over 50 with mild cognitive impairment (early memory problems) or Alzheimer's who can provide informed consent. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on anticoagulant therapy or have taken amyloid-reducing agents like aducanumab or lecanemab, you may not be eligible to participate.

What prior data suggests that this focused ultrasound technique is safe for Alzheimer's patients?

Research has shown that focused ultrasound treatments are well-tolerated by people with Alzheimer's disease. Earlier studies found that this method can safely open the blood-brain barrier, a protective layer around the brain, without damaging brain tissue. In some cases, it even helped reduce levels of harmful proteins associated with Alzheimer's. A meta-analysis, which combines results from several studies, confirmed that this approach is safe and effective in making the blood-brain barrier more permeable. This means treatments can reach the brain more easily. Overall, focused ultrasound appears to be a promising and safe option for Alzheimer's patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's Disease?

Researchers are excited about focused ultrasound treatment for Alzheimer's because it offers a novel approach by temporarily opening the blood-brain barrier (BBB). Unlike traditional treatments that primarily focus on managing symptoms with medications like cholinesterase inhibitors and memantine, this technique uses neuronavigation-guided ultrasound waves paired with microbubbles to enhance drug delivery directly to the brain. This method could potentially improve the effectiveness of existing treatments by allowing therapeutic agents to reach brain areas that are otherwise difficult to access, potentially slowing disease progression more effectively.

What evidence suggests that focused ultrasound is effective for Alzheimer's Disease?

Research has shown that focused ultrasound (FUS), which participants in this trial will receive, can safely and effectively open the blood-brain barrier (BBB) in people with Alzheimer's disease. This technique, used with tiny bubbles, helps treatments reach the brain more easily. Studies in mice demonstrated that FUS alone can lower levels of amyloid beta and tau proteins, which are linked to Alzheimer's, and improve memory. Early human trials also indicated that FUS can reduce these harmful proteins. Overall, FUS offers a promising method to make the brain more accessible to treatments for Alzheimer's. ^{2 4 5 6 7}

Who Is on the Research Team?

Grace McIlvain, PhD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for individuals over 50 with Alzheimer's Disease, confirmed by PET scans showing amyloid plaques and tau in the frontal lobe. Participants should have mild to moderate cognitive impairment (MMSE score of 12-26), low risk of stroke (MHIS ≤4), and minimal depression (GDS ≤6). They must be able to consent.

Inclusion Criteria

My PET scan shows tau protein in my brain's frontal lobe.

My score on a stroke-related scale is 4 or less.

I can understand and agree to the study's procedures and risks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles

1 day

1 visit (in-person)

Short-term Follow-up

Assessment of amyloid beta and tau protein load using PET tracers at 3 weeks after treatment

3 weeks (±1 week)

1 visit (in-person)

Long-term Follow-up

Assessment of amyloid beta and tau protein load using PET tracers at 3 months after treatment

3 months (±2 weeks)

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• FUS-induced BBB Opening

Trial Overview The study tests if focused ultrasound can safely open the blood-brain barrier in Alzheimer's patients, potentially reducing brain amyloid and tau proteins. It uses MRI, neuronavigation-guided ultrasound, contrast agents like Lumason, Dotarem, Amyvid for PET scans, and involves blood and urine tests.

How Is the Trial Designed?

Group I: Focused ultrasound treatment Experimental Treatment 10 Interventions

Neuronavigation-guided focused ultrasound treatment in Alzheimer's disease patients using a single-element transducer in conjunction with microbubbles.

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Published Research Related to This Trial

Focused ultrasound (FUS) combined with microbubbles has been shown to safely open the blood-brain barrier in animal studies, allowing therapeutic agents to enter the brain and potentially improve cognitive function in Alzheimer's disease.

Human studies indicate that repeated FUS treatments are well tolerated with minimal side effects, and they may enhance brain blood flow and neural function, which is associated with cognitive improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Applications of Focused Ultrasound (FUS) in Alzheimer's Disease Treatment: A Systematic Review on Both Animal and Human Studies. Liu, X., Naomi, SSM., Sharon, WL., et al.[2021]

In a phase I safety trial involving five patients with early to moderate Alzheimer's disease, focused ultrasound successfully and safely opened the blood-brain barrier without causing serious adverse events or worsening cognitive function over three months.

Although the procedure was safe, exploratory analysis showed no significant changes in beta-amyloid levels post-treatment, indicating that while the method is feasible, further research is needed to assess its efficacy in reducing Alzheimer's pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood-brain barrier opening in Alzheimer's disease using MR-guided focused ultrasound. Lipsman, N., Meng, Y., Bethune, AJ., et al.[2022]

Focused ultrasound (FUS) safely opened the blood-brain barrier (BBB) in eight participants with Alzheimer's disease, with no serious adverse effects reported, indicating its potential as a therapeutic approach.

Post-treatment imaging showed that BBB opening led to significant changes in brain fluid dynamics, suggesting a new pathway for fluid movement in the brain, which could have implications for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer's disease. Mehta, RI., Carpenter, JS., Mehta, RI., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40406679/

Efficacy and safety of focused ultrasound-mediated blood ... This meta-analysis underscores the potential of FUS as a non-invasive, safe, and effective method for enhancing BBB permeability in AD patients.

2. fusfoundation.org fusfoundation.org/posts/alzheimers-clinical-trial-final-results-published/

Alzheimer's Clinical Trial Final Results Published The trial used focused ultrasound plus microbubbles to open the blood-brain barrier (BBB) in patients with Alzheimer's disease.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024135645

A comprehensive review of advanced focused ultrasound ... The results of this study displayed that FUS can induce the BBB opening and internalization of Gd-loaded MBs in brain cells [92]. MRI technique ...

4. thejns.org thejns.org/view/journals/j-neurosurg/142/5/article-p1263.xml

Repetitive and extensive focused ultrasound–mediated ... Focused ultrasound (FUS)–mediated blood-brain barrier (BBB) opening is safe and potentially beneficial in patients with Alzheimer's disease (AD) ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308719

Ultrasound Blood–Brain Barrier Opening and Aducanumab ... Several studies have shown that focused ultrasound can safely and transiently open the blood–brain barrier in patients with Alzheimer's disease ...

6. fusfoundation.org fusfoundation.org/posts/alzheimers-disease-new-focused-ultrasound-clinical-trial-shows-safety-and-potential-clinical-benefits/

Alzheimer's Disease: New Focused Ultrasound Clinical ... The focused ultrasound–mediated BBB opening was shown to decrease amyloid plaques in some participants. Compared with baseline, amyloid levels ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724000220

Safety, Efficacy and Clinical Applications of Focused ... Pre-and early clinical data suggests that Focused Ultrasound (FUS) technology safely enhances BBB permeability without damaging brain tissue, enabling drug ...