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

25 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Low-Intensity Focused Ultrasound for pain?

Research shows that Low-Intensity Focused Ultrasound (LIFU) can help reduce pain from soft tissue injuries and increase pain relief duration in nerve injury models, especially in females. It is also used to safely modulate brain activity, which may help in managing pain and other conditions. ^{1 2 3 4 5}

Is low-intensity focused ultrasound safe for humans?

Research shows that low-intensity focused ultrasound (LIFU) is generally safe for humans, with no serious adverse effects reported. Some participants experienced mild symptoms like neck pain, attention problems, and muscle twitches, but these were not severe and often went away quickly. ^{2 4 6 7 8}

How is the treatment Low-Intensity Focused Ultrasound (LIFU) unique for pain management?

Low-Intensity Focused Ultrasound (LIFU) is unique because it is a non-invasive treatment that uses sound waves to target specific areas of the brain or nervous tissue with high precision, without the need for surgery or drugs. This allows for reversible modulation of pain responses, making it different from traditional pain treatments like medication or invasive procedures. ^{2 3 4 5 9}

What is the purpose of this trial?

Investigating the relationship between input pressure of low-intensity focused ultrasound and an evoked potential in both eeg and fMRI.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Alleviation Effects and Mechanisms of Low-intensity Focused Ultrasound on Pain Triggered by Soft Tissue Injury. [2021]

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

Low Intensity Focused Ultrasound Increases Duration of Anti-Nociceptive Responses in Female Common Peroneal Nerve Injury Rats. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

MR thermometry imaging for low intensity focused ultrasound modulation of spinal nervous tissue. [2023]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

7. United States 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. [2020]

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

Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation. [2023]

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

Transcranial focused ultrasound stimulation with high spatial resolution. [2021]