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

6 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment FUS-induced BBB Opening for Alzheimer's Disease?

Research shows that focused ultrasound (FUS) can safely and temporarily open the blood-brain barrier (BBB) in Alzheimer's patients, allowing better delivery of treatments to the brain. Studies in animals and early human trials suggest this method can help reduce Alzheimer's-related brain changes and improve cognitive function. ^{1 2 3 4 5}

Is focused ultrasound safe for humans?

Focused ultrasound (FUS) has been shown to be generally safe in humans, with studies reporting that it is well tolerated and does not cause serious side effects. In trials with Alzheimer's patients, FUS was used to open the blood-brain barrier safely and reversibly, with no significant adverse events or cognitive decline observed. ^{1 2 3 4 5}

How is the FUS-induced BBB Opening treatment different from other Alzheimer's treatments?

The FUS-induced BBB Opening treatment is unique because it uses focused ultrasound to temporarily open the blood-brain barrier, allowing therapeutic agents to enter the brain more effectively. This noninvasive approach is different from traditional treatments that struggle to deliver drugs past the blood-brain barrier. ^{1 2 4 5 6}

What is the purpose of this trial?

The primary purpose of this phase 1b study is to further assess the safety and reversibility of focused ultrasound induced blood-brain barrier opening (FUS-BBBO) in participants with Alzheimer´s Disease (AD) using a single-element transducer with neuronavigation guidance. Preliminary results from our phase 1a study demonstrate that our neuronavigation-guided FUS system was capable of safely and transiently open the BBB in participants with AD. The information collected in this new study may be used to design future clinical trials to ultimately provide a viable alternative for treatment of AD in a safe and noninvasive manner. Our secondary objective includes the assessment of the therapeutic efficacy of FUS-BBBO in reducing amyloid beta and neurofibrillary tangles, the main hallmark pathologies of AD, using PET tracers. Based on our preclinical studies in AD transgenic mouse models, FUS-BBBO alone was able to reduce both the amyloid beta and tau protein load, resulting in improvements in behavioral tasks assessing memory. Therefore, in this new study, the effect of FUS-BBBO on the amyloid beta and tau protein load in patients with AD will be assessed through the use of PET tracers.

Research Team

Grace McIlvain, PhD

Principal Investigator

Columbia University

Eligibility Criteria

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.

My memory test score is between 12 and 26.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer's disease. [2023]

2. United States 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Blood-brain barrier opening in Alzheimer's disease using MR-guided focused ultrasound. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Acute Effects of Focused Ultrasound-Induced Blood-Brain Barrier Opening on Anti-Pyroglu3 Abeta Antibody Delivery and Immune Responses. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Ultrasound as a versatile tool for short- and long-term improvement and monitoring of brain function. [2023]