LIFU for Anxiety

Overseen By Jessica Florig, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Disqualifiers: Claustrophobia, Neurologic disorder, Cardiovascular, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how a new, noninvasive brain treatment might help people with anxiety. The treatment uses low-intensity focused ultrasound (LIFU) to alter brain activity before participants complete certain tasks. Participants will encounter different scenarios, some involving mild shocks or rewards, while researchers record their physiological responses. The trial seeks individuals with high or low anxiety levels who do not have conditions like claustrophobia or certain neurological disorders.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in anxiety treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that LIFU is safe for anxiety treatment?

Research has shown that Low-Intensity Focused Ultrasound (LIFU) is generally safe. Studies have found that people tolerate LIFU well. For instance, one study with 25 participants confirmed its safety, reporting very few side effects. This suggests that LIFU is usually safe to use.

LIFU targets deep areas of the brain linked to anxiety and depression. This is a new and exciting field of research, and early results are promising. While researchers continue to study LIFU, several trials support its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Low-Intensity Focused Ultrasound (LIFU) for treating anxiety because it offers a non-invasive, targeted approach that could directly modulate brain activity. Unlike typical anxiety treatments, which often involve medications like SSRIs that can take weeks to affect mood and have side effects, LIFU has the potential to provide quicker, more precise relief with fewer side effects. This technique utilizes sound waves to influence specific brain regions, which could lead to personalized and efficient anxiety management, making it a promising alternative to conventional therapies.

What evidence suggests that LIFU is effective for anxiety?

Research has shown that Low-Intensity Focused Ultrasound (LIFU), the treatment under study in this trial, can potentially alter brain activity, which might help reduce anxiety symptoms. Studies have found that LIFU can target specific brain areas related to anxiety and depression. This noninvasive method, which does not involve surgery or entering the body, offers a significant advantage over some traditional treatments. Early findings suggest LIFU may provide relief with fewer side effects compared to other anxiety treatments. Although more research is needed, current evidence is promising for those seeking new ways to manage anxiety. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with either high or low levels of anxiety. It's not specified who can't join, but typically those with certain medical conditions or taking conflicting medications might be excluded.

Inclusion Criteria

High or low trait anxiety

Exclusion Criteria

Claustrophobia

Contraindications to MRI (implants)

History of alcohol or drug dependence

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo fMRI and CT scans to image bone and brain tissue

1 week

1 visit (in-person)

Treatment

Participants receive noninvasive brain stimulation using LIFU and undergo threat tasks with physiological monitoring

2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LIFU

Trial Overview The study is testing the effects of a noninvasive brain stimulation technique called Low-intensity focused ultrasound (LIFU) on managing anxiety, compared to a sham (placebo-like) procedure before participants do a task designed to measure their response to stress.

How Is the Trial Designed?

Group I: NPU-c Experimental Treatment 2 Interventions

Participants will be presented with a moving line. When the line reaches a certain point - an event will occur. This event will either be a painful shock or a monetary reward. Startle sounds will occur throughout. 3 study visits will occur - identical conditions for the participant, testing 2 brain regions and 1 sham visit.

Group II: NPU Experimental Treatment 2 Interventions

Participant will be presented with a series of images (cues) and sounds. Three conditions will occur - a no shock (N), predictable shock (P), and unpredictable shock (U). In P, shocks will only occur with the cue. In U, shocks will happen at any time. Participants will be told which condition they are in throughout the task. Startle sounds will occur throughout. 3 Study visits will occur - identical conditions for the participant, testing 2 brain regions and 1 sham visit.

LIFU is already approved in United States for the following indications:

Approved in United States as Focused Ultrasound for:

• Essential Tremor
• Parkinson’s Disease

Who Is Running the Clinical Trial?

Virginia Polytechnic Institute and State University

Lead Sponsor

Trials

162

Recruited

26,900+

Published Research Related to This Trial

Low intensity focused ultrasound (LIFU) is a promising non-invasive technology that can precisely modulate brain activity, offering a new approach to studying and potentially treating psychiatric illnesses.

LIFU has been shown to safely affect both cortical and subcortical brain regions, distinguishing it from other neuromodulatory techniques due to its spatial precision and reversible effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation-A Paradigm Shift in Psychiatric Research. Arulpragasam, AR., van 't Wout-Frank, M., Barredo, J., et al.[2022]

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]

High-intensity focused ultrasound (HIFU) is a safe and non-invasive treatment option for advanced pancreatic cancer, as shown in a study of 224 cases with no severe complications reported.

While some patients experienced mild side effects like increased serum amylase levels and gastrointestinal dysfunction, the overall safety profile was positive, indicating that careful preparation and execution are essential for successful outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of high-intensity focused ultrasound in patients with pancreatic cancer. Wang, K., Zhu, H., Meng, Z., et al.[2022]

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]

The study developed a 3D printed, wearable helmet designed for Low-Intensity Focused Ultrasound (LIFU) that allows for precise and noninvasive brain stimulation, enhancing the accuracy of neuromodulation techniques.

Testing showed that the helmet effectively positions the target within the focal volume of the ultrasound, indicating its potential for improved spatial resolution in brain stimulation applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a subject-specific guide system for Low-Intensity Focused Ultrasound (LIFU) brain stimulation. Joe, H., Pahk, KJ., Park, S., et al.[2020]

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]

A study involving 120 participants evaluated the safety of low intensity transcranial focused ultrasound (LIFU) for neuromodulation, finding no serious adverse effects and only mild to moderate symptoms reported by 7 participants, which were generally transient.

The symptom profile from LIFU was similar to other non-invasive brain stimulation methods, suggesting that LIFU is a safe option for neuromodulation with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans. Legon, W., Adams, S., Bansal, P., et al.[2021]

In a study of 372 women with symptomatic uterine fibroids who underwent MR-HIFU, the overall rate of adverse events (AEs) was low at 8.9%, with no major AEs reported, indicating that MR-HIFU is a safe treatment option.

The only significant risk factor for AEs was the treatment of type II uterine fibroids, suggesting that while MR-HIFU is generally safe, certain types of fibroids may carry a higher risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occurrence of adverse events after magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) therapy in symptomatic uterine fibroids-a retrospective case-control study. Kociuba, J., Łoziński, T., Zgliczyńska, M., et al.[2023]

Microfocused Ultrasound with Visualization (MFU-V) has a well-established safety profile, showing only mild and transient side effects like tenderness and redness, with rare adverse events typically linked to improper technique.

When used correctly, MFU-V treatments are safe, with most side effects resolving quickly and without lasting effects, indicating its efficacy in cosmetic dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the safety profile for microfocused ultrasound with visualization. Hitchcock, TM., Dobke, MK.[2022]

High-intensity focused ultrasound (HIFU) is an effective non-invasive treatment for various solid tumors, including liver and pancreatic cancers, particularly beneficial for patients who cannot undergo surgery due to medical complications.

HIFU serves as a valid treatment option for liver tumors in patients with poor liver function and is also used as a bridging therapy for those awaiting liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of high-intensity focused ultrasound. She, WH., Cheung, TT., Jenkins, CR., et al.[2017]

Citations

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

A Comprehensive Review of Low-Intensity Focused ... In this study, we provide a review of the most recent LIFU literature covering three key domains: 1) the history of focused ultrasound ...

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

A Comprehensive Review of Low-Intensity Focused ... In this study, we provide a review of the most recent LIFU literature covering three key domains: 1) the history of focused ultrasound technology, comparing it ...

3. reporter.nih.gov reporter.nih.gov/project-details/10209047

Low intensity focused ultrasound - NIH RePORTER PROJECT SUMMARY/ABSTRACT Current treatments for depression and anxiety are often limited by partial efficacy and significant side effects.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05147142

NCT05147142 | Low Intensity Focused Ultrasound: a New ... In this study, the investigators will test if this technique can be used to change brain activity in areas that are connected to depression and anxiety symptoms ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05467085

Imaging-Guided Low Intensity Focused Ultrasound (LIFU) This research study is to investigate the safety, feasibility, and possible therapeutic benefits of a technology called Low Intensity Focused Ultrasound ...

6. fusfoundation.org fusfoundation.org/posts/clinical-trial-investigates-low-intensity-focused-ultrasound-for-depression/

Clinical Trial Investigates Low-Intensity ... Preliminary data show that LIFU may be able to reach deep structures of the brain involved with depression and anxiety that traditional ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05147142

NCT05147142 | Low Intensity Focused Ultrasound: a New ... The primary objectives of this study are to test the safety and tolerability of LIFU, evaluate the feasibility of using LIFU to reduce brain activity, and ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0022395623004776

A pilot study of low-intensity focused ultrasound for ... Low-intensity focused ultrasound shows promise as a clinical intervention for anxiety. · Safety and tolerability of LIFUP protocol confirmed among 25 ...