Low-Intensity Focused Ultrasound for Clinical Follow-up

Overseen By Jessica Florig, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Disqualifiers: Claustrophobia, Pacemaker, Pregnancy, Neurologic disorder, others

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

Compensation: Varies

Number of Visits: 6

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different durations of low-intensity focused ultrasound (LIFU) treatment affect muscle movements and brain activity. Researchers aim to understand how this technique might assist with addiction, pain, and mental health challenges. Participants will undergo brain imaging and tests to assess their brain and muscle responses to the treatment. This trial may suit individuals who speak English, do not have metal implants, and have no history of neurological disorders or significant head injuries. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could lead to new treatments for various conditions.

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 technique is safe for noninvasive neuromodulation?

Research shows that low-intensity focused ultrasound (LIFU) is generally safe for humans. Studies have found that LIFU non-invasively targets specific brain areas. Participants in earlier trials reported only minor side effects, such as mild sensations or temporary discomfort, with no serious issues commonly noted.

For instance, one study examined LIFU's safety and found it well-tolerated by participants, with no major safety concerns. Another study compared participant reports and neurological tests, confirming LIFU's safety for brain treatments. These findings are encouraging and suggest that LIFU is a safe option for those considering clinical trials using this ultrasound technology. ^{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 technique to potentially improve neurological conditions. Unlike traditional treatments that often rely on medication or surgery, LIFU uses sound waves to target specific brain areas without cutting into the body. This method can be applied in different durations, both intermittently and continuously, allowing for flexible treatment options. By recording responses with TMS (transcranial magnetic stimulation) and EMG (electromyography), researchers hope to better understand and optimize its effects, paving the way for safer and more effective interventions.

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

Research has shown that Low-Intensity Focused Ultrasound (LIFU) can temporarily alter brain function. Studies have found that LIFU is safe and can accurately target specific brain regions. This trial will test six different durations of LIFU application, both intermittent and continuous, to evaluate its effects. Researchers are exploring this technique for its potential to address issues like addiction, pain, and mental health problems. Early results suggest that LIFU can affect muscle movements when combined with other methods like transcranial magnetic stimulation (TMS). These effects are under further study to determine how LIFU might be used for future treatments. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals willing to use a medication monitoring system. It's not suitable for those with pacemakers, metal implants, history of significant head injury or substance dependence, active CNS-affecting medical conditions, pregnancy, or claustrophobia.

Inclusion Criteria

Patients must be willing to use a Pillsy medication event monitoring system

I can speak and read English.

Patient is NOT to be deemed ineligible during the recruitment process if they do not have a smart phone

Exclusion Criteria

History of alcohol or drug dependence

Presence of pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants

I have had a head injury that made me unconscious for more than 10 minutes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo structural imaging, fMRI, CT, and receive LIFU and TMS to study muscle contractions

3 weeks

6 study sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low-Intensity Focused Ultrasound

Trial Overview The study tests how different durations of Low-Intensity Focused Ultrasound (LIFU) affect muscle contractions. Participants will undergo brain imaging and stimulation techniques while their muscle responses are recorded.

How Is the Trial Designed?

Group I: Duration Trials Experimental Treatment 1 Intervention

Six different durations (three intermittent and three continuous) of LIFU application will be tested across six study sessions. Response recorded using TMS and EMG.

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

In a phase 1 study involving 15 participants, intense ultrasound treatment for facial and neck tissues was found to be safe, with no significant adverse effects reported and only mild discomfort experienced by patients.

Histological analysis showed that the treatment created consistent thermal injury zones in the dermis without damaging the epidermis, indicating a targeted and effective approach for skin rejuvenation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pilot study of intense ultrasound therapy to deep dermal facial skin and subcutaneous tissues. Gliklich, RE., White, WM., Slayton, MH., et al.[2012]

In a study of 372 women with symptomatic uterine fibroids who underwent MR-HIFU, the overall rate of adverse events (AEs) was low at 8.9%, with no major AEs reported, indicating that MR-HIFU is a safe treatment option.

The only significant risk factor for AEs was the treatment of type II uterine fibroids, suggesting that while MR-HIFU is generally safe, certain types of fibroids may carry a higher risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occurrence of adverse events after magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) therapy in symptomatic uterine fibroids-a retrospective case-control study. Kociuba, J., Łoziński, T., Zgliczyńska, M., et al.[2023]

In a study of 191 patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU), 81.7% of those with low-risk disease achieved durable cancer control, indicating HIFU is particularly effective for this group.

The study found that while HIFU showed decreasing efficacy in intermediate and high-risk patients, overall survival rates at 5 years were high (86.3% overall and 98.4% cancer-specific), suggesting it can be a viable treatment option, though higher-risk patients may require additional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single application of high-intensity focused ultrasound as a first-line therapy for clinically localized prostate cancer: 5-year outcomes. Pfeiffer, D., Berger, J., Gross, AJ.[2022]

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 (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]

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]

Microfocused Ultrasound with Visualization (MFU-V) has a well-established safety profile, showing only mild and transient side effects like tenderness and redness, with rare adverse events typically linked to improper technique.

When used correctly, MFU-V treatments are safe, with most side effects resolving quickly and without lasting effects, indicating its efficacy in cosmetic dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the safety profile for microfocused ultrasound with visualization. Hitchcock, TM., Dobke, MK.[2022]

Citations

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

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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05467085

Imaging-Guided Low Intensity Focused Ultrasound (LIFU) This research study is to investigate the safety, feasibility, and possible therapeutic benefits of a technology called Low Intensity Focused Ultrasound ...

3. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1211566/full

Low-intensity focused ultrasound targeting the nucleus ... Outcomes were the safety, tolerability, and feasibility during the LIFU procedure and throughout the 90-day follow-up. Outcomes also included ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05997030

Low-Intensity Focused Ultrasound (LIFU) Neuromodulation The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome ...

5. nature.com nature.com/articles/s41598-024-68827-4

Five-year follow-up after a single US-guided high intensity ... A single HIFU intervention let to a substantial reduction in size, pain, and palpability with its most potential effect during the first 12 months.

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

Safety of Clinical Ultrasound Neuromodulation - PMC Transcranial ultrasound holds much potential as a safe, non-invasive modality for navigated neuromodulation, with low-intensity focused ultrasound (FUS) and ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1094715924006627

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 assess its impact ...

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/posts/clinical-trial-investigates-low-intensity-focused-ultrasound-for-depression/

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