LIFU for Alzheimer's Disease

Overseen By Kiley Everson, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ali Rezai

Must be taking: AChEI, Memantine

Disqualifiers: Seizure disorder, Chronic pulmonary disorders, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 week

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether Low-Intensity Focused Ultrasound (LIFU) is safe and tolerable for individuals with mild memory and thinking problems due to Alzheimer's disease. The study explores how LIFU affects brain activity, which might assist with these cognitive issues. Participants should have mild cognitive impairment related to Alzheimer's and be able to communicate their sensations during the procedure. The trial seeks individuals who have been stable on certain Alzheimer's medications for at least 45 days and can undergo an MRI. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatments for Alzheimer's-related cognitive issues.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on AChEI or memantine, you must have been on a stable dose for at least 45 days.

What prior data suggests that Low-Intensity Focused Ultrasound (LIFU) is safe for neuromodulation in patients with mild cognitive impairment due to Alzheimer's disease?

Research has shown that Low-Intensity Focused Ultrasound (LIFU) is generally safe for people with Alzheimer's disease. In past studies, patients tolerated the treatment well, with no reports of serious side effects. Another study confirmed LIFU's safety, indicating it doesn't cause significant harm.

Although researchers are still testing LIFU, these early results are encouraging. The main goal is to ensure its safety before assessing its effectiveness in alleviating symptoms. While more research is needed, current information suggests that LIFU is a safe option for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for Alzheimer's Disease, which often rely on medications to manage symptoms, Low-Intensity Focused Ultrasound (LIFU) offers a non-invasive technique that targets the brain directly. Researchers are excited about LIFU because it uses sound waves to stimulate brain activity, potentially enhancing cognitive function without the need for drugs. This method could open up new possibilities for treating Alzheimer's by modulating brain networks in a way that current medication-based therapies cannot achieve.

What evidence suggests that Low-Intensity Focused Ultrasound (LIFU) is effective for Alzheimer's disease?

Research has shown that Low-Intensity Focused Ultrasound (LIFU), which participants in this trial will receive, could help treat Alzheimer's disease by temporarily opening the blood-brain barrier. This opening might allow medications to reach the brain more effectively. Early results suggest LIFU could help adjust brain activity in people with mild memory problems due to Alzheimer's. Although still under study, LIFU is emerging as an intriguing non-invasive treatment option for various brain conditions. ^{3 5 6 7 8}

Who Is on the Research Team?

Ali Rezai, MD

Principal Investigator

WVU Rockefeller Neuroscience Institute

Are You a Good Fit for This Trial?

This trial is for men and women aged 45-85 who can communicate during the procedure, have mild cognitive impairment due to Alzheimer's, and are not pregnant. Participants must be able to consent and if taking certain Alzheimer's medications, they should be on a stable dose for at least 45 days.

Inclusion Criteria

You can express feelings during the LIFU procedure.

You possess the capacity to provide informed consent.

I am between 45 and 85 years old and not pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Exablate low intensity focused ultrasound neuromodulation

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Low-Intensity Focused Ultrasound (LIFU)

Trial Overview The study is testing Low-Intensity Focused Ultrasound (LIFU) as a neuromodulation treatment in patients with mild cognitive impairment from Alzheimer's. It’s an early-stage study focused on understanding how safe and tolerable this technique is.

How Is the Trial Designed?

Group I: Neuromodulation Experimental Treatment 1 Intervention

Subjects meeting eligibility criteria will undergo Exablate low intensity focused ultrasound neuromodulation

Low-Intensity Focused Ultrasound (LIFU) is already approved in United States, Canada, Japan for the following indications:

Approved in United States as Low-Intensity Focused Ultrasound (LIFU) for:

• Mild Cognitive Impairment (MCI) due to Alzheimer's disease
• Research use for neuromodulation

Approved in Canada as Low-Intensity Focused Ultrasound (LIFU) for:

• Research use for neuromodulation in Alzheimer's disease

Approved in Japan as Low-Intensity Focused Ultrasound (LIFU) for:

• Research use for neuromodulation in Alzheimer's disease

Who Is Running the Clinical Trial?

Ali Rezai

Lead Sponsor

Trials

6

Recruited

90+

Published Research Related to This Trial

In a pilot study involving four patients with Alzheimer's disease, low-intensity transcranial focused ultrasound (tFUS) was found to increase cerebral glucose metabolism in specific brain regions, indicating potential therapeutic effects.

Patients showed mild improvements in cognitive functions, such as memory and executive function, after the tFUS treatment, and no adverse events were reported, suggesting that this method may be safe for use in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer's disease. Jeong, H., Im, JJ., Park, JS., et al.[2021]

Low-intensity focused ultrasound (LIFU) treatment significantly improved spasticity in male Sprague-Dawley rats with spinal cord injury after 4 weeks of daily sessions, indicating its potential as an effective therapy.

The mechanism of LIFU's efficacy may involve a reduction in the expression of growth associated protein 43 (Gap43), suggesting it helps to modulate neuroplasticity and axon regeneration below the injury site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proteomics Reveals the Effect of Low-Intensity Focused Ultrasound on Spasticity After Spinal Cord Injury. Wang, B., Zhao, H., Chen, M., et al.[2023]

High-density gel polymer matrices are effective couplants for low-intensity focused ultrasound (LIFU) neuromodulation, showing low acoustic attenuation (3.3%) and minimal beam distortion, making them suitable for clinical use.

The study highlights the importance of using standardized methods for preparing these gels to ensure consistent performance, as factors like thickness and de-gassing can significantly affect acoustic transmission and pressure attenuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. Strohman, A., In, A., Stebbins, K., et al.[2023]

Low intensity focused ultrasound (LiFUS) can effectively disrupt the blood-brain barrier (BBB) in a dose-dependent manner, with increased tracer uptake in the brain observed when using higher microbubble and cavitation doses.

The timing of tracer administration is crucial; the highest accumulation of small solutes occurs when administered just before LiFUS, but significant uptake is also seen up to 6 hours post-treatment, indicating a biphasic response in BBB permeability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model. Arsiwala, TA., Sprowls, SA., Blethen, KE., et al.[2023]

Low-intensity focused ultrasound (LIFU) therapy significantly reduced cancer-related neuropathic pain in a retrospective study of 22 patients, with a p-value of less than 0.001 indicating strong statistical significance.

Approximately 76.5% of patients responded positively to LIFU therapy, suggesting it may be an effective treatment option for neuropathic pain, particularly that caused by chemotherapy, and it has a minimal side effect profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary effects of low-intensity focused ultrasound treatment program for cancer-related neuropathic pain. Patel, AA., Zhukosvky, M., Sidharthan, S., et al.[2022]

Low-intensity focused ultrasound (LIFUS) is a promising noninvasive technique that can modulate human brain activity, showing effects like suppressing cortical evoked potentials and altering sensory/motor task outcomes in studies involving human subjects.

The proposed mechanisms of LIFUS include cavitation and direct effects on neural ion channels, suggesting it could be developed for non-surgical treatments of neurological disorders, although optimal protocols are still being refined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity ultrasound neuromodulation: An overview of mechanisms and emerging human applications. Fomenko, A., Neudorfer, C., Dallapiazza, RF., et al.[2019]

Citations

1. fusfoundation.org fusfoundation.org/diseases-and-conditions/alzheimers-disease/

Alzheimer's Disease A clinical trial with low intensity focused ultrasound treatment is being used for treatment of early cognitive disability or Alzheimer's ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11333319/

Focused ultrasound therapy for Alzheimer's disease Focused ultrasound shows promise as a non-invasive technique for disrupting the blood–brain barrier, potentially enhancing drug delivery directly to the brain.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05997030

Low-Intensity Focused Ultrasound (LIFU) Neuromodulation ... LIFU for neuromodulation in patients with mild cognitive impairment ( MCI) due to Alzheimer's disease. Detailed Description. The primary objective is to ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1094715924006627

A Comprehensive Review of Low-Intensity Focused ... Low-intensity focused ultrasound (LIFU) is gaining increased interest as a potential therapeutic modality for a range of neuropsychiatric diseases.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11700779/

A Comprehensive Review of Low-Intensity Focused ... Low-intensity focused ultrasound (LIFU) is gaining increased interest as a potential therapeutic modality for a range of neuropsychiatric diseases.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40267289/

Repeated neuromodulation with low-intensity focused ... Repeated neuromodulation with low-intensity focused ultrasound in patients with Alzheimer's disease. J Alzheimers Dis. 2025 Jun;105(3):955 ...

7. 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 ... Results from a novel clinical trial (NCT06158789) using focused ultrasound to treat Alzheimer's disease have now been published in the Journal of Neurosurgery.

8. fusfoundation.org fusfoundation.org/posts/alzheimers-disease-focused-ultrasound-neuromodulation-clinical-trial-completed-in-korea/

Alzheimer's Disease Results from an Alzheimer's clinical trial testing low-intensity focused ultrasound (LIFU) neuromodulation have now been published.