Neuromodulation for Pain Management

Overseen By Jessica W Florig, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Disqualifiers: Claustrophobia, 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: 3 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how noninvasive brain stimulation affects brain signals, potentially aiding issues related to addiction, pain, and mental health. Participants will receive low-intensity focused ultrasound (LIFU), a type of neuromodulation therapy, to observe changes in brain activity, followed by MRI scans to track these changes. Ideal candidates are healthy volunteers who speak English and have no history of neurological disorders or certain medical implants. Participants will visit the study site four times for tests and questionnaires. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes people with active medical disorders or treatments that affect the central nervous system. It's best to discuss your specific medications with the trial team.

What prior data suggests that this neuromodulation technique is safe for pain management?

Research has shown that low-intensity focused ultrasound (LIFU) is safe for humans. Studies have found that LIFU does not harm movement abilities or brain health. One report examined LIFU's safety through participant feedback and brain tests, finding it well-tolerated. No major safety issues emerged. Overall, these findings suggest that LIFU is a promising and safe method for stimulating the brain in pain management. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about low-intensity focused ultrasound (LIFU) for pain management because it offers a non-invasive way to modulate brain activity, potentially reducing pain without the need for medications like opioids or NSAIDs, which can have significant side effects. Unlike traditional treatments that often involve systemic drug administration, LIFU targets specific brain regions, minimizing the impact on the rest of the body. This precision could lead to fewer side effects and a more tailored approach to pain management, making it a promising alternative to current pain relief methods.

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

Research shows that low-intensity focused ultrasound (LIFU), which participants in this trial may receive, can alter animal behavior in response to pain. Studies have found that LIFU affects brain areas involved in pain processing. In healthy individuals, LIFU has lowered pain sensitivity and reduced pain during lab tests. Regular LIFU sessions have led to lasting positive changes in brain pain processing. These findings suggest that LIFU could offer a new method for managing pain by targeting the brain's pain pathways. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy volunteers from any ethnic background who can understand and speak English. It's not suitable for pregnant individuals, those with certain metal implants, a history of significant head injury, claustrophobia, neurological disorders like Parkinson's or epilepsy, active central nervous system conditions such as Alzheimer's, or a history of substance dependence.

Exclusion Criteria

I have a neurological condition like Parkinson's, Epilepsy, or Essential Tremor.

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

Contraindications to CT: pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive low-intensity focused ultrasound (LIFU) and undergo fMRI scans to measure changes in brain signaling

3 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low-intensity Focused Ultrasound

Trial Overview The study tests how low-intensity focused ultrasound (LIFU) affects brain activity related to pain. Participants undergo MRI and CT scans along with LIFU treatment. Changes in brain signals are monitored through fMRI after LIFU while experiencing controlled heat sensations. The study spans over four visits including questionnaires and vital signs monitoring.

How Is the Trial Designed?

Group I: LIFU, heat evoked fMRI signals Experimental Treatment 1 Intervention

fMRI resting and heat evoked signals performed after LIFU application to known brain region of interest or active sham region (within participant all conditions tested).

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

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) 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 prototype Low Intensity Focused Ultrasound (LIFU) stimulator was successfully developed and tested on a Göttingen minipig, showing its potential for non-invasive neuromodulation.

The study demonstrated that targeted stimulation of the hypothalamus using LIFU resulted in reversible increases in heart rate and blood pressure, indicating a direct physiological effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prototype stimulator system for noninvasive Low Intensity Focused Ultrasound delivery. Mulgaonkar, AP., Singh, RS., Babakhanian, M., et al.[2016]

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]

Transcranial focused ultrasound (tFUS) effectively suppresses pain by stimulating the periaqueductal gray (PAG) in a rat model, demonstrating its potential as a non-invasive analgesic method.

The study found that tFUS stimulation activates the PAG without causing significant temperature changes or tissue damage, indicating a safe approach for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Focused Ultrasound Stimulation of Periaqueductal Gray for Analgesia. Zhang, T., Wang, Z., Liang, H., 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]

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]

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/NCT06906211

Low Intensity Focused Ultrasound for Chronic Pain: High ... The preliminary data indicate that LIFU to PI reduces laboratory measures of central sensitization and evoked pain in healthy controls but there was no such ...

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

The efficacy and mechanisms of low-intensity transcranial ... More notably, switching from a single intervention to daily sessions for 14 days resulted in lasting positive changes that could last for ...

5. fusfoundation.org fusfoundation.org/posts/low-back-pain-clinical-data-show-focused-ultrasound-is-safe-and-effective/

Low Back Pain: Clinical Data Show Focused Ultrasound is ... FUSMobile recently published positive clinical trial results using high-intensity focused ultrasound (HIFU) to treat low back pain.

6. 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.

7. 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 ...

8. nature.com nature.com/articles/s41598-020-62265-8

A retrospective qualitative report of symptoms and safety ... We provide an evaluation of the safety of LIFU for human neuromodulation through participant report and neurological assessment with a comparison of ...

9. 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 ...