Neuromodulation for Pain Management

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Virginia Polytechnic Institute and State University

Disqualifiers: Claustrophobia, Pregnancy, Neurologic disorders, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses low-intensity focused ultrasound (LIFU) to gently stimulate specific areas of the brain. Focused ultrasound can stimulate a specific point of tissue and can be a noninvasive method for acupoint stimulation. It targets people dealing with addiction, pain, and mental health issues who may not respond well to typical treatments. The sound waves temporarily change brain activity, which could help improve their symptoms.

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 data supports the effectiveness of this treatment for pain management?

Research shows that low-intensity focused ultrasound (LIFU) can modulate pain responses in animal models and is a promising non-invasive tool for brain stimulation to manage pain. It has been shown to safely affect brain activity, which could help in pain management. ^{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 to moderate symptoms like neck pain, attention problems, muscle twitches, and anxiety, but these were not severe and often resolved quickly. ^{1 2 3 6 7}

How is Low-intensity Focused Ultrasound (LIFU) treatment different from other pain management treatments?

Low-intensity Focused Ultrasound (LIFU) is unique because it is a non-invasive treatment that uses sound waves to precisely target and modulate brain activity, unlike traditional methods that may involve surgery or medication. It offers reversible effects and can reach deep brain areas without the need for incisions, setting it apart from other neuromodulation techniques like transcranial magnetic or electrical stimulation. ^{1 2 3 5 8}

Research Team

Eligibility Criteria

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.

Inclusion Criteria

Healthy volunteers, all ethnicities, who understand and speak English.

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

Trial Timeline

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

Treatment Details

Interventions

• Low-intensity Focused Ultrasound (Neuromodulation)

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.

Participant Groups

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).

Who Is Running the Clinical Trial?

Virginia Polytechnic Institute and State University

Lead Sponsor

Trials

162

Recruited

26,900+

Dr. Cyril Clarke

Virginia Polytechnic Institute and State University

Chief Medical Officer since 2018

DVM from University of Pretoria

Dr. Timothy Sands

Virginia Polytechnic Institute and State University

Chief Executive Officer since 2014

PhD in Materials Science from University of California, Berkeley

Findings from Research

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 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]

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]

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]

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]

References

1. 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]

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

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Transcranial Focused Ultrasound Stimulation of Periaqueductal Gray for Analgesia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. [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. Korea (South) pubmed.ncbi.nlm.nih.gov

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

8. Netherlands pubmed.ncbi.nlm.nih.gov

A prototype stimulator system for noninvasive Low Intensity Focused Ultrasound delivery. [2016]