Low-Intensity Focused Ultrasound for Pain

Overseen By Jessica Florig, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Disqualifiers: Claustrophobia, Pacemaker, Pregnancy, Neurologic disorders, others

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

Approved in 2 Jurisdictions 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 a new method for managing pain using low-intensity focused ultrasound, a treatment that employs sound waves. Researchers aim to determine how varying sound wave pressures affect brain activity, measured with EEG (a test that records brain waves) and fMRI (a type of brain scan). Participants are divided into groups, each experiencing different pressures or undergoing safety checks. Suitable candidates have no history of neurological disorders or head injuries that caused unconsciousness for more than 10 minutes. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research in pain management.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have an active medical disorder or are undergoing treatment that affects the central nervous system, you may not be eligible to participate.

What prior data suggests that low-intensity focused ultrasound is safe for pain management?

Research shows that low-intensity focused ultrasound (LIFU) could be a promising way to treat pain. Studies have found that LIFU can alter how the brain processes pain, potentially reducing pain sensations. In animal tests, LIFU changed behaviors related to pain, suggesting it might work similarly in humans.

The treatment is noninvasive, meaning it doesn't involve surgery or entering the body, which usually lowers the risk of serious side effects. However, there is limited information about side effects in humans. Since the trial is in an early stage, detailed human data is not yet available. Because LIFU is being tested for safety, any major issues would likely have halted the research by now.

Overall, LIFU appears well-tolerated in early studies, but more research is needed to fully understand its safety in humans. Participants in clinical trials will help researchers gather this important information. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using low-intensity focused ultrasound (LIFU) for pain management because it offers a non-invasive way to potentially alleviate pain without the need for drugs or surgery. Unlike standard pain treatments like medications or physical therapy, LIFU targets the brain's somatosensory cortex with precise ultrasound waves to modulate pain perception. This method could provide quicker relief and fewer side effects compared to conventional approaches. Additionally, the ability to apply different pressures and monitor effects using techniques like fMRI and EEG gives researchers valuable insights into how effectively LIFU can alter brain activity related to pain.

What evidence suggests that low-intensity focused ultrasound is effective for pain?

Research shows that low-intensity focused ultrasound (LIFU), which participants in this trial will receive, can alter how the brain processes pain. Studies have found that LIFU can influence pain-related behaviors in animals by targeting specific brain regions. Researchers are exploring this method for treating chronic pain and movement issues, particularly in the spine. As a non-invasive technique, it does not involve surgery, making it an appealing option for pain management. Overall, early results suggest that LIFU could offer a promising drug-free approach to managing pain. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals experiencing nociceptive or somatic pain. Specific eligibility criteria are not provided, so it's important to contact the study organizers for detailed requirements on who can participate.

Exclusion Criteria

Contraindications to MRI: including pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants

Contraindications to CT: pregnancy

History of alcohol or drug dependence (through self-report)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Check

A small cohort undergoes high pressure LIFU application with follow-up MRI conducted 24-72 hours post to ensure safety

1 week

1 visit (in-person)

Treatment

Participants receive LIFU application at one of three pressures, with EEG and fMRI collected pre and post application

2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a symptom questionnaire administered 1 week post intervention

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Low-intensity Focused Ultrasound

Trial Overview The study is examining how different pressures of low-intensity focused ultrasound (high, medium, and low) affect brain activity as seen in EEG and fMRI scans.

How Is the Trial Designed?

Group I: fMRI Experimental Treatment 3 Interventions

Electrical stimulation utilized to generate SEPs, performed pre and post LIFU application. One of three LIFU pressures will be applied. One per study visit (3), randomized order. fMRI collected throughout visit (outcome measure).

Group II: Safety Check - high pressure application Experimental Treatment 1 Intervention

Small cohort to be collected prior to other study cohorts. Highest of 3 pressures of interest will be applied to the S1 (somatosensory cortex) with a follow-up MRI conducted 24-72 hours post.

Group III: EEG Experimental Treatment 3 Interventions

Electrical stimulation utilized to generate SEPs, performed pre and post LIFU application. One of three LIFU pressures will be applied. One per study visit (3), randomized order. EEG collected throughout visit (outcome measure).

Low-intensity Focused Ultrasound is already approved in United States, European Union for the following indications:

Approved in United States as LIFU for:

• Research purposes for neurological conditions such as depression, addiction, and pain management

Approved in European Union as LIFU for:

• Research purposes for neurological conditions such as depression, addiction, and pain management

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]

The dual-crossed transducer system achieved high spatial resolution in targeting small brain regions in mice, with a focal volume of under 0.52 μm³ and a focal diameter of 1 mm, making it effective for precise neuromodulation.

In vivo experiments demonstrated successful brain stimulation in wild-type mice, evidenced by observable movements, confirming the system's capability for noninvasive and specific targeting of brain circuits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound stimulation with high spatial resolution. Kim, S., Jo, Y., Kook, G., et al.[2021]

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]

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]

Transcranial focused ultrasound (tFUS) can precisely target specific brain areas with low acoustic intensity, effectively modulating brain excitability and potentially promoting neural plasticity for neurorehabilitation.

The review highlights the excellent safety profile of tFUS, but emphasizes the need for new safety guidelines and recommendations for its use in healthy volunteers and clinical settings, based on a comprehensive analysis of acoustic parameters and their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation. Lee, W., Weisholtz, DS., Strangman, GE., et al.[2023]

Low intensity focused ultrasound (liFUS) can modulate pain responses without causing significant heating, as demonstrated in swine models, with magnetic resonance thermometry imaging (MRTI) effectively measuring temperature changes of less than 2.0 °C at the L5 dorsal root ganglion (DRG).

The study identified that referenceless MRTI is capable of accurately detecting small thermal changes, which is crucial for establishing safe parameters for future liFUS therapy in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR thermometry imaging for low intensity focused ultrasound modulation of spinal nervous tissue. Olinger, C., Vest, J., Tarasek, M., et al.[2023]

A systematic review of 33 studies on low-intensity transcranial focused ultrasound stimulation (TFUS) indicates that adverse effects are very rare, with most studies showing no significant negative outcomes even when safety limits were exceeded.

However, at high stimulation intensities, TFUS can potentially cause serious issues like hemorrhage, cell death, and unintended blood-brain barrier opening, highlighting the need for further research to establish clear safety guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. Pasquinelli, C., Hanson, LG., Siebner, HR., et al.[2020]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S000649712401838X

Low-intensity transcranial focused ultrasound suppresses ... We demonstrate that tFUS stimulation at pain-processing brain circuits can significantly alter pain-associated behaviors in mouse models in vivo.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12209223/

Low-intensity focused ultrasound of the spine in the treatment ... In this work, we review current advances in LIFU of the spine region for the treatment of chronic neuropathic pain and movement disorders.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05145426

Investigation of Low-intensity Focused Ultrasound for ... This project examines the effects of noninvasive brain stimulation on pain. The investigators believe this study will help to better understand possible ...

4. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-025-02096-y

The efficacy and mechanisms of low-intensity transcranial ... Low-intensity transcranial ultrasound stimulation (LITUS) is an emerging non-invasive neuromodulation technique for pain treatment, with the ...

5. fusfoundation.org fusfoundation.org/diseases-and-conditions/neuropathic-pain/

Neuropathic Pain A clinical trial is using low intensity focused ultrasound to do deep brain stimulation to help patients with chronic pain. Virginia Polytechnic ...

6. ashpublications.org ashpublications.org/blood/article/144/10/1101/516866/Low-intensity-transcranial-focused-ultrasound

Low-intensity transcranial focused ultrasound suppresses ... Low-intensity transcranial focused ultrasound suppresses pain by modulating pain-processing brain circuits.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9338851/

Low-Intensity Focused Ultrasound Alleviates Chronic ... Low-intensity focused ultrasound (LIFU) is a potential noninvasive method to alleviate allodynia by modulating the central nervous system.