LIFU for Chronic Pain

Overseen By Jessica Florig, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Carilion Clinic

Disqualifiers: Seizures, Pseudo-seizures, MRI contraindications, others

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

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores low-intensity focused ultrasound (LIFU) to manage chronic pain in individuals with complex regional pain syndrome (CRPS) or fibromyalgia (FM). The researchers aim to determine if LIFU can alter brain pain processing and potentially provide relief. Participants may receive either the actual LIFU treatment or a sham (fake) treatment for comparison. Individuals diagnosed with CRPS or FM who frequently experience daily pain might be suitable candidates for this study. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could lead to new pain management solutions.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that low-intensity focused ultrasound (LIFU) is safe for neuromodulation in chronic pain patients?

Research has shown that low-intensity focused ultrasound (LIFU) is generally safe for humans. Studies have found that LIFU can reduce pain without causing significant harm. For instance, when applied to a specific brain area, LIFU lowered pain levels in patients. Another study found it safe and effective for treating low back pain.

For fibromyalgia (FM), LIFU safely reduces pain by affecting the central nervous system, which sends pain signals. Research also indicates it can safely change brain activity, providing temporary relief without lasting side effects.

In both complex regional pain syndrome (CRPS) and FM, LIFU has been used without major problems when applied correctly. While more research is needed, current studies support its safety for treating chronic pain conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Low-intensity Focused Ultrasound (LIFU) for chronic pain because it offers a unique, non-invasive approach to managing pain conditions like Complex Regional Pain Syndrome (CRPS) and Fibromyalgia (FM). Unlike standard treatments, which often include medications such as opioids or antidepressants, LIFU uses sound waves to target and potentially alter nerve activity, aiming to relieve pain without the side effects associated with drugs. This technique not only minimizes physical discomfort but also has the potential to provide quicker relief by directly modulating pain pathways in the body. The use of LIFU as a targeted therapy represents a promising step forward in pain management, offering hope for more effective and safer pain relief.

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

Research has shown that low-intensity focused ultrasound (LIFU) can reduce pain in individuals with long-term conditions like Complex Regional Pain Syndrome (CRPS) and Fibromyalgia (FM). In this trial, participants will receive either real LIFU or sham LIFU in different arms. Previous studies demonstrated that using LIFU on the posterior insula, a brain region involved in pain processing, lowered pain levels during certain tests. Additionally, LIFU is considered a promising method for managing chronic nerve pain, which results from nerve damage. Some trial results suggested it works as well as other established treatments, with no reported side effects. These findings indicate that LIFU may offer relief for those dealing with chronic pain conditions. ^{1 6 7 8 9}

Who Is on the Research Team?

Elizabeth Stringer, MD

Principal Investigator

Carilion Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with chronic pain conditions, specifically diagnosed with fibromyalgia or complex regional pain syndrome by a Carilion physician. Participants must meet certain diagnostic criteria and cannot have contraindications to MRI or CT scans, nor a history of seizures.

Inclusion Criteria

I have been diagnosed with fibromyalgia by a Carilion physician.

I have been diagnosed with CRPS type I or II by a Carilion doctor.

Exclusion Criteria

I have a history of seizures.

You are not able to have an MRI for medical reasons.

I cannot undergo CT scans due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

MRI and CT anatomical scans are obtained, and baseline clinical measurements of the target limb are recorded

1 session

1 visit (in-person)

Treatment

Participants undergo LIFU or sham treatment with QST and clinical measurements

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in perceived pain, skin temperature, and swelling circumference

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low-intensity Focused Ultrasound (LIFU)
• Sham Low-intensity focused ultrasound (LIFU)

Trial Overview The study is testing the effectiveness of Low-intensity Focused Ultrasound (LIFU) as a neuromodulation treatment for chronic pain. Some participants will receive real LIFU while others will get a sham procedure to compare outcomes.

How Is the Trial Designed?

Group I: LIFU - CRPS Active Control 1 Intervention

Real LIFU application for CRPS cohort.

Group II: LIFU - FM Active Control 1 Intervention

Real LIFU application for FM cohort.

Group III: SHAM - CRPS Placebo Group 1 Intervention

Sham LIFU application for CRPS cohort.

Group IV: SHAM - FM Placebo Group 1 Intervention

Sham LIFU application for FM cohort.

Who Is Running the Clinical Trial?

Carilion Clinic

Lead Sponsor

Trials

85

Recruited

15,400+

Virginia Polytechnic Institute and State University

Collaborator

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]

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]

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]

Low-intensity focused ultrasound (LIFU) therapy significantly reduced cancer-related neuropathic pain in a retrospective study of 22 patients, with a p-value of less than 0.001 indicating strong statistical significance.

Approximately 76.5% of patients responded positively to LIFU therapy, suggesting it may be an effective treatment option for neuropathic pain, particularly that caused by chemotherapy, and it has a minimal side effect profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary effects of low-intensity focused ultrasound treatment program for cancer-related neuropathic pain. Patel, AA., Zhukosvky, M., Sidharthan, S., et al.[2022]

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]

Citations

1. 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.

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. fusfoundation.org fusfoundation.org/diseases-and-conditions/pain-chronic/

Pain, Chronic A clinical trial at Virginia Tech is using low intensity focused ultrasound to treat patients who have complex regional pain syndromes or ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05751096/low-intensity-focused-ultrasound-for-insular-neuromodulation-in-chronic-pain?mp=s&id=369&slug=reflex-sympathetic-dystrophy-syndrome-rsds

Low-Intensity Focused Ultrasound For Insular ... Study investigating the potential benefit for chronic pain patients (CRPS and FM) using low-intensity focused ultrasound for neuromodulation.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8261174/

Focused Ultrasound (FUS) for Chronic Pain Management Results at 6 months were considered comparable to RF denervation. No adverse side effect was reported [119]. This trial provides preliminary ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9599299/

Safety of Clinical Ultrasound Neuromodulation - PMC For clinical applications, TPS has been shown to be safe, when sticking to our published patient protocols and exclusion/inclusion criteria, such as no signs of ...

7. 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.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04339972

Low Intensity Focused Ultrasound Pulses (LIFUP) to ... The purpose of this study is to examine whether stimulation of the anterior nuclei of the thalamus via LIFUP induces analgesia. We hypothesize that suppression ...

9. 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 ... Low Back Pain: Clinical Data Show Focused Ultrasound is Safe and Effective. Published: May 22, 2024. Key Points. FUSMobile recently published ...