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 study is a prospective, single-center, single-arm early feasibility study, to establish safety and tolerability of LIFU for neuromodulation in patients with mild cognitive impairment ( MCI) due to Alzheimer's disease.

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.

How is the LIFU treatment for Alzheimer's disease different from other treatments?

LIFU (Low-Intensity Focused Ultrasound) is unique because it uses sound waves to temporarily open the blood-brain barrier, allowing for potential delivery of treatments directly to the brain, which is not possible with most other Alzheimer's treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Low-Intensity Focused Ultrasound (LIFU) for Alzheimer's Disease?

Research shows that Low-Intensity Focused Ultrasound (LIFU) can open the blood-brain barrier (a protective layer around the brain) and potentially improve brain activity. In a pilot study, LIFU was explored for its effects on Alzheimer's patients, focusing on brain metabolism and cognitive function, although its full effectiveness and safety in humans are still being studied. ^{1 2 3 5 6}

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

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]

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]

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 (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) 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) 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]

Citations

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

Low-intensity ultrasound neuromodulation: An overview of mechanisms and emerging human applications. [2019]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer's disease. [2021]

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

Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Preliminary effects of low-intensity focused ultrasound treatment program for cancer-related neuropathic pain. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model. [2023]

6. Turkey pubmed.ncbi.nlm.nih.gov

Proteomics Reveals the Effect of Low-Intensity Focused Ultrasound on Spasticity After Spinal Cord Injury. [2023]