Low-intensity Focused Ultrasound for Chronic Pain

Overseen By Wynn Legon, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Disqualifiers: Claustrophobia, Neurologic disorder, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for managing chronic pain using low-intensity focused ultrasound, a form of non-invasive brain stimulation. Researchers aim to determine if sound waves can safely alter brain activity to reduce pain. Participants will undergo brain scans and tests to assess their body's response to pain. Ideal candidates are English speakers without certain medical devices, such as pacemakers or metal implants, among other criteria. As an unphased trial, this study provides participants the chance to contribute to groundbreaking research in pain management.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if your treatment has potential effects on the central nervous system, it might be a concern.

What prior data suggests that this low-intensity focused ultrasound device is safe for chronic pain treatment?

Research shows that low-intensity focused ultrasound (LIFU) is generally easy for people to handle. Studies have found that LIFU can temporarily change brain activity without causing major harm. Specifically, one study discovered that a single LIFU session on a brain area related to feeling reduced pain signals effectively. This suggests LIFU can be safe and might help manage pain. While some people might feel mild discomfort during the procedure, serious side effects are rare. Overall, current research supports the safety of LIFU for changing brain activity, making it a promising option for treating chronic pain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Low-intensity Focused Ultrasound (LIFU) is unique because it offers a non-invasive approach to managing chronic pain. While standard options like medication or physical therapy primarily focus on symptom relief, LIFU uses targeted sound waves to potentially modulate nerve activity and reduce pain. This technique could provide pain relief without the side effects associated with drugs, which excites researchers about its potential as a safer, more precise pain management tool.

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

Research has shown that low-intensity focused ultrasound (LIFU) can alter brain activity to help reduce pain. In this trial, participants will receive either LIFU or a sham application. One study demonstrated that using LIFU on the posterior insula, a brain region linked to pain perception, lowered pain levels during certain tests. Another study found that targeting the primary somatosensory cortex, an area that processes sensory information, with LIFU significantly reduced pain after just one session. These promising results suggest that LIFU might effectively manage chronic pain by temporarily altering brain activity. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals with chronic pain. It's not suitable for those who have contraindications to MRI/CT/EEG, claustrophobia, certain implants like pacemakers or cochlear implants, pregnant women, people with active medical disorders affecting the brain, a history of significant head injury or substance dependence.

Exclusion Criteria

You have a medical condition that makes it unsafe for you to have an MRI, CT scan, or EEG.

You have a history of a brain or nerve disorder.

You have had a head injury where you were unconscious for more than 10 minutes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo structural imaging, fMRI, CT, and LIFU/Sham application with quantitative sensory testing

3 weeks

Multi visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low Intensity Focused Ultrasound

Trial Overview The study tests Low Intensity Focused Ultrasound (LIFU) as a noninvasive treatment for chronic pain. Participants will undergo imaging tests and have their brain activity altered by sound waves while their physiological responses are monitored.

How Is the Trial Designed?

Group I: Pain Trials Experimental Treatment 1 Intervention

Multi visit - LIFU/Sham application, with quantitative sensory testing (using peltier device).

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 (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 (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]

Focused ultrasound (FUS) is a promising noninvasive technique for managing chronic pain, with approved uses for thalamotomy in neuropathic pain and treatment of pain from bone metastases.

Different intensities of FUS can produce varying effects: low-intensity ultrasound (LILFUS) can facilitate or suppress neural activity, while high-intensity focused ultrasound (HIFU) can ablate tissue, showing potential for treating conditions like knee osteoarthritis and refractory chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound (FUS) for Chronic Pain Management: Approved and Potential Applications. di Biase, L., Falato, E., Caminiti, ML., et al.[2021]

In a study involving 11 patients with chronic neuropathic pain, low-energy focused ultrasound (FUS) significantly reduced pain levels, with median current pain decreasing from 10.0 to 7.0 after 4 weeks, indicating its efficacy as a treatment.

The procedure was found to be safe, with no reported side effects such as burns or seizures, and no significant changes observed in follow-up brain imaging, suggesting that low-energy tcNgFUS is a noninvasive option for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Energy Transcranial Navigation-Guided Focused Ultrasound for Neuropathic Pain: An Exploratory Study. Shin, DH., Son, S., Kim, EY.[2023]

In a study involving 30 male Sprague Dawley rats with common peroneal nerve injury, low intensity focused ultrasound (liFUS) applied to the L5 dorsal root ganglion significantly altered neuronal activity, increasing pyramidal neuron spike frequency in the primary somatosensory cortex (SI) and reducing interneuron firing in the anterior cingulate cortex (ACC).

These changes in neuronal activity occurred 80 to 120 minutes after liFUS treatment and may correlate with improved sensory thresholds, suggesting a potential mechanism for how liFUS can help alleviate neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of low intensity focused ultrasound on neuronal activity in pain processing regions in a rodent model of common peroneal nerve injury. Bao, J., Byraju, K., Patel, VJ., 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06906211

Low Intensity Focused Ultrasound for Chronic Pain: High ... In this study, the research team will use low-intensity focused ultrasound (LIFU) to temporarily change brain activity in a brain region that is known to be ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001359

Low-intensity focused ultrasound to the posterior insula ... LIFU to the posterior insula reduced pain ratings during temporal summation of pain but not conditioned pain modulation.

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

A Comprehensive Review of Low-Intensity Focused ... Low-intensity focused ultrasound (LIFU) is gaining increased interest as a potential therapeutic modality for a range of neuropsychiatric diseases.

4. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2025.1606672/full

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

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

Low-intensity transcranial focused ultrasound suppresses ... Our findings indicate that a single-session focused ultrasound stimulation to the primary somatosensory cortex (S1) significantly attenuates ...

6. 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 ...