Low-Intensity Focused Ultrasound for Various Conditions

Overseen By Jessica Florig, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Must be taking: Buprenorphine, Methadone

Must not be taking: Daily opiates

Disqualifiers: Neuropathic pain, Schizophrenia, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Low-Intensity Focused Ultrasound (LIFU) to assess its effects on pain, cravings, and anxiety. It targets individuals with chronic back pain persisting for at least three months, who also experience ongoing issues with opioid use and anxiety. Participants will attend several visits to measure their pain, cravings, and anxiety before and after receiving either the LIFU treatment or a placebo. As an unphased trial, this study provides a unique opportunity to explore a novel approach to managing chronic pain and related issues.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it requires participants to be in treatment for opioid use disorder with buprenorphine or methadone, so you may need to continue those medications.

What prior data suggests that Low-Intensity Focused Ultrasound is safe for pain, craving, and anxiety?

Research has shown that Low-Intensity Focused Ultrasound (LIFU) is generally safe and well-tolerated. For instance, one study used ultrasound at or below the FDA's safe intensity level and found it posed a Non-Significant Risk (NSR) to participants. Another study supported its safety by reviewing feedback from trial participants. These findings suggest that LIFU is safe for use in clinical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Low-Intensity Focused Ultrasound (LIFU) because it offers a non-invasive way to address pain, cravings, and anxiety. Unlike traditional treatments that might involve medication or more invasive procedures, LIFU uses sound waves to target specific brain areas without the need for surgery or drugs. This technique is particularly appealing because it minimizes side effects and recovery time, providing a safer alternative to manage these conditions. Additionally, the ability to precisely focus on brain regions potentially allows for more targeted and effective treatment, which could lead to quicker and more noticeable improvements for patients.

What evidence suggests that Low-Intensity Focused Ultrasound is effective for pain, craving, and anxiety?

Research has shown that Low-Intensity Focused Ultrasound (LIFU) can improve mood and reduce feelings of worry. Recipients of LIFU treatment reported feeling happier and less anxious. Studies also indicate that LIFU can decrease pain levels by about 1 point on a 10-point scale. This treatment alters brain activity in areas linked to pain and mood. Overall, LIFU appears promising in reducing pain, anxiety, and cravings. Participants in this trial will undergo assessments on pain, craving, and anxiety measures before and after receiving either LIFU or a sham intervention. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with chronic pain, opioid use disorder, and anxiety disorders. The eligibility criteria are not fully listed here, so additional requirements may apply.

Inclusion Criteria

Meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for current opiate use disorder as diagnosed by the Structured Clinical Interview for DSM-5

I have widespread pain with a high severity score.

I am currently being treated for opioid addiction with buprenorphine or methadone.

Exclusion Criteria

I have been diagnosed with a brain condition or abnormality by a neuroradiologist.

I have been diagnosed with schizophrenia or schizo-affective disorder.

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Low Intensity Focused Ultrasound (LIFU) or Sham treatment and complete measures of pain, craving, and anxiety pre and post intervention

4 weeks

Multiple visits

Follow-up

Participants are monitored for changes in heart rate, mood, respiration rate, and blood pressure, and for treatment-emergent adverse events

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low-Intensity Focused Ultrasound

Trial Overview The study investigates the effects of Low-Intensity Focused Ultrasound (LIFU) on reducing pain, cravings related to opioid use, and symptoms of anxiety in patients with these conditions.

How Is the Trial Designed?

Group I: Pain, Craving, and Anxiety measures Experimental Treatment 2 Interventions

Multi visit - LIFU/Sham. Participants will complete pain, craving, and anxiety measures pre and post intervention.

Who Is Running the Clinical Trial?

Virginia Polytechnic Institute and State University

Lead Sponsor

Trials

162

Recruited

26,900+

Washington DC VA Medical Center

Collaborator

Trials

2

Recruited

100+

Salem VA Medical Center

Collaborator

Trials

2

Recruited

30+

Published Research Related to This Trial

High-intensity focused ultrasound (HIFU) is an effective non-invasive treatment for various solid tumors, including liver and pancreatic cancers, particularly beneficial for patients who cannot undergo surgery due to medical complications.

HIFU serves as a valid treatment option for liver tumors in patients with poor liver function and is also used as a bridging therapy for those awaiting liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of high-intensity focused ultrasound. She, WH., Cheung, TT., Jenkins, CR., et al.[2017]

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 (LiFUS) significantly enhances the accumulation of chemotherapy drugs in brain metastases, which is crucial for treating metastatic breast cancer, as traditional therapies have low efficacy.

In a preclinical model, combining LiFUS with chemotherapy (Doxil and paclitaxel) resulted in a median survival of 60 days and slower tumor progression compared to other treatment combinations, suggesting that LiFUS could be a promising strategy for improving drug delivery to brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy. Arsiwala, TA., Blethen, KE., Wolford, CP., et al.[2023]

In a study of 20 patients with inoperable pancreatic cancer, high-intensity focused ultrasound (HIFU) significantly reduced pain levels, with an average decrease of 2.87 points on the numeric rating scale (NRS) and a 57.3% reduction from baseline in 19 out of 20 patients.

HIFU not only alleviated physical pain but also significantly improved emotional pain aspects, demonstrating its effectiveness as a palliative treatment option for managing pain in advanced pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[High-intensity focused ultrasound (HIFU) for tumor pain relief in inoperable pancreatic cancer : Evaluation with the pain sensation scale (SES)]. Marinova, M., Strunk, HM., Rauch, M., et al.[2022]

In a study using bovine liver, the accuracy of ultrasound monitoring for tissue necrosis caused by pulsed high intensity focused ultrasound (PHIFU) was significantly improved by using a correlation function-based evaluation, which achieved an 85% accuracy rate compared to only 51% for gray-scale evaluations.

This suggests that relying solely on gray-scale changes in ultrasound images is insufficient for accurately monitoring tissue damage during PHIFU treatment, highlighting the need for more sensitive evaluation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Accuracy of correlation function method for evaluating pulsed high intensity focused ultrasound]. Zhao, X., Zou, J., Wu, F., et al.[2016]

In a study involving 10 patients with various skin lesions, 20 MHz high-intensity focused ultrasound (HIFU) demonstrated a 97% cure rate for actinic keratosis (AK), with most lesions healing within 1-2 weeks and no scarring observed.

HIFU was found to be effective and safe for treating AK and showed potential for use in basal cell carcinoma and Kaposi sarcoma, suggesting it could be a promising alternative or supplement to traditional photodynamic therapy (PDT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-frequency (20 MHz) high-intensity focused ultrasound: New Treatment of actinic keratosis, basal cell carcinoma, and Kaposi sarcoma. An open-label exploratory study. Serup, J., Bove, T., Zawada, T., et al.[2021]

Pulsed high-intensity focused ultrasound (PHIFU) was found to create greater liquefaction necrosis in liver tissue compared to continuous high-intensity focused ultrasound (CHIFU) at the same energy dose, indicating its potential for more effective tissue ablation.

PHIFU at a duty cycle of 60% showed lower energy efficiency compared to CHIFU, but it may enhance tissue destruction through cavitation effects, suggesting that optimizing duty cycles could improve ablation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Study of Pulsed Versus Continuous High-Intensity Focused Ultrasound Ablation Using In Vitro and In Vivo Models. Wang, Y., Wang, Q., Luo, Y., et al.[2020]

Low-intensity focused ultrasound (LIFU) treatment significantly improved spasticity in male Sprague-Dawley rats with spinal cord injury after 4 weeks of daily sessions, indicating its potential as an effective therapy.

The mechanism of LIFU's efficacy may involve a reduction in the expression of growth associated protein 43 (Gap43), suggesting it helps to modulate neuroplasticity and axon regeneration below the injury site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proteomics Reveals the Effect of Low-Intensity Focused Ultrasound on Spasticity After Spinal Cord Injury. Wang, B., Zhao, H., Chen, M., et al.[2023]

The combination of adriamycin-microbubble-PLGA nanoparticle complexes (ADM-NMCs) with low-intensity focused ultrasound (LIFU) significantly enhanced tumor inhibition in rabbits with VX2 liver tumors, resulting in the highest volume inhibition rate and apoptotic index compared to other treatment groups.

Rabbits treated with ADM-NMCs and LIFU had the longest median survival time of 71 days, indicating that this method not only targets the tumor effectively but also improves overall survival, showcasing a promising approach for localized chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity focused ultrasound mediated localized drug delivery for liver tumors in rabbits. Gong, Y., Wang, Z., Dong, G., et al.[2018]

In a clinical trial involving 152 healthy patients, high-intensity focused ultrasound (HIFU) was found to be a safe method for reducing localized abdominal fat, with no serious device-related adverse events reported.

The treatment effectively targeted subcutaneous adipose tissue, leading to normal healing and minimal discomfort, with optimal results achieved at lower energy levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a novel high-intensity focused ultrasound device for ablating subcutaneous adipose tissue for noninvasive body contouring: safety studies in human volunteers. Gadsden, E., Aguilar, MT., Smoller, BR., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12562471/

Using Low-Intensity Focused Ultrasound to Treat Depression ... Findings revealed that individuals who received active LIFU experienced improvements in mood states of worry and increased feelings of happiness ...

2. fusfoundation.org fusfoundation.org/posts/treating-pain-with-focused-ultrasound-two-neuromodulation-clinical-trials/

Two Neuromodulation Clinical Trials LIFU noninvasively reduced pain by roughly 1 point on a 10 point scale and altered autonomic responses to the painful stimuli. See the Journal ...

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

The efficacy and mechanisms of low-intensity transcranial ... A total of thirteen studies were included in the review. These studies demonstrated LITUS's potential in managing various types of pain among ...

4. 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, ...

5. 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 ...

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

A Comprehensive Review of Low-Intensity Focused ... Regardless, given LIFU has revealed a strong safety profile, research is rapidly moving beyond basic mechanistic studies to clinical trials to ...

7. fusfoundation.org fusfoundation.org/posts/clinical-trial-investigates-low-intensity-focused-ultrasound-for-depression/

Clinical Trial Investigates Low-Intensity ... A clinical trial is investigating the safety and feasibility of using low-intensity focused ultrasound to address anxiety and depression.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05467085

Imaging-Guided Low Intensity Focused Ultrasound (LIFU) LIFU intensity will be at or below FDA safety limit of 720 mW/cm^2 Ispta, which resulted in an IRB/FDA determination of Non-Significant Risk (NSR) in our study ...

9. 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 ...