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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This project examines the effects of various durations of noninvasive neuromodulation on muscle contractions. The investigators believe this study will help to better understand noninvasive brain stimulation techniques that may have the potential to aid in addiction, pain, and mental health issues. Participants undergo structural imaging, a functional Magnetic Resonance Image (fMRI) and computed tomography (CT). These images are used to align the low-intensity focused ultrasound (LIFU) and transcranial magnetic stimulation (TMS) devices to temporarily change brain activity. Electromyography (EMG) will be used to record muscle contractions of the hand.

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.

Is Low-Intensity Focused Ultrasound (LIFU) generally safe for humans?

Research on similar ultrasound therapies shows that they are generally safe, with mild and temporary side effects like tenderness and redness. Rarely, more serious effects can occur, often due to incorrect use, but these are uncommon. ^{1 2 3 4 5}

How is Low-Intensity Focused Ultrasound treatment different from other treatments for this condition?

Low-Intensity Focused Ultrasound (LIFU) is unique because it uses sound waves to target specific areas in the body without surgery, unlike traditional treatments that may involve more invasive procedures. This non-invasive approach can potentially reduce recovery time and minimize side effects. ^{6 7 8 9 10}

Eligibility Criteria

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

Must understand and speak English

I can speak and read English.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[The study of clinical application of high intensity focused ultrasound in non-invasive therapy for liver cancer]. [2006]

2. England 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. [2023]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Review of the safety profile for microfocused ultrasound with visualization. [2022]

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

Clinical pilot study of intense ultrasound therapy to deep dermal facial skin and subcutaneous tissues. [2012]

6. China pubmed.ncbi.nlm.nih.gov

[Accuracy of correlation function method for evaluating pulsed high intensity focused ultrasound]. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Comparative Study of Pulsed Versus Continuous High-Intensity Focused Ultrasound Ablation Using In Vitro and In Vivo Models. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Salvage radiotherapy after high intensity focused ultrasound for prostate cancer. [2021]

9. Canada pubmed.ncbi.nlm.nih.gov

Salvage HIFU for biopsy confirmed local prostate cancer recurrence after radical prostatectomy and radiation therapy: Case report and literature review. [2020]

10. England 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. [2022]