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

80 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Low Intensity Focused Ultrasound (LIFU) for chronic pain?

Research shows that low intensity focused ultrasound (LIFU) can reduce pain levels in patients with chronic neuropathic pain, as seen in a study where patients experienced a decrease in pain scores after treatment. Additionally, LIFU has been shown to modulate pain responses in animal models, suggesting its potential as a non-invasive treatment for chronic pain. ^{1 2 3 4 5}

Is Low-Intensity Focused Ultrasound (LIFU) 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, muscle twitches, and anxiety, but these were not severe and often went away quickly. ^{5 6 7 8 9}

How is the treatment Low Intensity Focused Ultrasound (LIFU) different from other treatments for chronic pain?

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 nerves, potentially altering brain activity and reducing pain without surgery or medication. Unlike traditional pain treatments, LIFU can disrupt the blood-brain barrier to allow targeted drug delivery and modulate neuronal activity directly, offering a novel approach for managing chronic pain. ^{1 3 8 9 10}

What is the purpose of this trial?

This project examines the effects of noninvasive brain stimulation on pain. The investigators believe this study will help to better understand possible treatments for chronic pain patients. Participants undergo structural imaging, a functional Magnetic Resonance Image (fMRI) and computed tomography (CT). These images are used to align the low-intensity focused ultrasound (LIFU) device which uses sound waves to temporarily change brain activity. Pain testing is done using a small device that will increase/decrease the temperature of the skin. Brain signals are collected using electroencephalography (EEG). Heart rate, blood pressure, and skin moisture will be monitored as well.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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) 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 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]

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]

References

1. 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]

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

Focused Ultrasound (FUS) for Chronic Pain Management: Approved and Potential Applications. [2021]

3. Ireland 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. [2022]

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

Low-Energy Transcranial Navigation-Guided Focused Ultrasound for Neuropathic Pain: An Exploratory Study. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

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. 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]

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

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

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

Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model. [2023]

10. England pubmed.ncbi.nlm.nih.gov

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