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

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is examining the effects of noninvasive brain stimulation on anxiety. Low-intensity focused ultrasound (LIFU) will be utilized to neuromodulate the brain prior to a task (NPU). Physiological recordings will be taken throughout (EEG, EMG, HR, BP, RR, GSR).

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 data supports the effectiveness of the treatment LIFU for anxiety?

LIFU (Low-Intensity Focused Ultrasound) is a promising non-invasive treatment that can precisely target and modulate specific brain areas, which may help in managing anxiety. It has been shown to safely affect brain activity without serious side effects, making it a potential option for treating psychiatric conditions. ^{1 2 3 4 5}

Is Low-Intensity Focused Ultrasound (LIFU) safe for use in humans?

In a study with 120 participants using Low-Intensity Focused Ultrasound (LIFU) for brain stimulation, no serious side effects were reported. Some mild to moderate symptoms like neck pain, attention problems, and muscle twitches were noted, but they were similar to other non-invasive brain treatments and resolved quickly. ^{5 6 7 8 9}

How is LIFU treatment different from other treatments for anxiety?

LIFU (Low-Intensity Focused Ultrasound) is unique because it noninvasively stimulates specific areas of the brain with high precision, unlike traditional anxiety treatments that often involve medication or talk therapy. This technique allows for targeted neuromodulation without the need for surgery or drugs, potentially offering a new way to manage anxiety with minimal side effects. ^{2 3 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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) 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]

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]

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

Clinical applications of high-intensity focused ultrasound. [2017]

2. Ireland pubmed.ncbi.nlm.nih.gov

Development of a subject-specific guide system for Low-Intensity Focused Ultrasound (LIFU) brain stimulation. [2020]

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation-A Paradigm Shift in Psychiatric Research. [2022]

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

A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety evaluation of high-intensity focused ultrasound in patients with pancreatic cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Ultrasound-guided high-intensity focused ultrasound treatment of breast fibroadenoma-a multicenter experience. [2020]

8. England 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Review of the safety profile for microfocused ultrasound with visualization. [2022]

10. Turkey pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

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

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

Ultrasound Stimulation of Periaqueductal Gray Induces Defensive Behaviors. [2021]