Focused Ultrasound for Anxiety Disorders

Overseen By Christopher T Sege, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Anticholinergics, Neuroleptics, Sedatives, Opiates

Disqualifiers: Substance use disorder, Psychotic disorder, Seizure disorder, others

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

Compensation: Varies

Number of Visits: 3

Duration: 2 days

40 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

You may need to stop certain medications to join the trial. Specifically, you cannot participate if you are currently taking anticholinergic, neuroleptic, or sedative/hypnotic medications. However, you can continue taking SSRIs, cholinesterase inhibitors, or NMDA receptor antagonists if you have been on a stable dose for at least four weeks before joining.

What data supports the effectiveness of the treatment Transcranial Focused Ultrasound for anxiety disorders?

Research shows that Magnetic Resonance-guided Focused Ultrasound (MRgFUS) has been effective in treating various conditions like uterine fibroids, movement disorders, and neuropathic pain by precisely targeting and treating specific areas in the body. This suggests potential for its use in treating anxiety disorders, as it can target brain areas involved in these conditions. ^{1 2 3 4 5}

Is focused ultrasound generally safe for humans?

The safety of focused ultrasound, including techniques like MRgFUS and tFUS, has been studied for various conditions. For example, microfocused ultrasound has shown only mild and temporary side effects like tenderness and redness, with rare serious issues often linked to incorrect use. While more research is needed, especially for brain applications, these techniques are generally considered safe when used properly. ^{2 6 7 8 9}

How does focused ultrasound treatment for anxiety disorders differ from other treatments?

Focused ultrasound is unique because it is a non-invasive treatment that uses sound waves to target specific areas of the brain without surgery. Unlike traditional treatments, it can precisely ablate (destroy) or modulate brain tissue, offering a new approach for treating anxiety disorders. ^{1 2 10 11 12}

What is the purpose of this trial?

This is a study to find out if a cutting-edge technology called transcranial focused ultrasound (tFUS) can be used to treat how people with anxiety or related concerns cope with emotional situations. tFUS is a brain stimulation technology that causes temporary changes in the activity of deep brain areas without a need for any surgery or other permanent or invasive procedures. This study is recruiting participants who recently started treatment for anxiety or a related concern to come in for 3 visits at the Medical University of South Carolina. At the first visit, participants will do interviews and surveys asking about anxiety and related concerns, and they do tasks where they respond to emotional pictures while brain activity is measured using magnetic resonance imaging (MRI). At the next two visits, participants again do a task where they see and react to emotional images, and this time the task is done once before and again once after receiving tFUS that either actively causes temporary changes (lasting for about an hour) in a targeted brain area or is not active (no changes elicited). At each tFUS visit, responses are measured with sensors worn on the hand, arms, face, and head (these visits do not involve MRI). Each visit in this study is expected to last between 2 - 3 hours. This study is not a treatment study, but it could help improve treatment in the future. Participants in this study are paid for their time.

Research Team

Christopher Sege, PhD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for individuals who have recently started treatment for anxiety or related issues. They should be able to attend three sessions at the Medical University of South Carolina and participate in tasks involving emotional responses, both with and without brain stimulation via tFUS.

Inclusion Criteria

I have been diagnosed with an anxiety disorder or PTSD.

Is able to read consent document and provide informed consent

English is a first or primary fluent language

Exclusion Criteria

Lifetime diagnosis of psychotic disorder or bipolar mania

Currently taking chronic opiate medications or substances

I do not have a seizure disorder that prevents brain stimulation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete interviews, surveys, and tasks with MRI to assess anxiety and related concerns

1 day

1 visit (in-person)

Treatment

Participants undergo tasks with active and sham tFUS stimulation on separate days, with physiological responses measured

2 days

2 visits (in-person)

Follow-up

Participants are monitored for changes in anxiety and physiological responses post-stimulation

4 weeks

Treatment Details

Interventions

• Transcranial Focused Ultrasound

Trial Overview The study tests transcranial focused ultrasound (tFUS), a non-invasive brain stimulation method, to see if it can influence how people with anxiety respond to emotional situations. Participants will receive either active tFUS that temporarily alters brain activity or sham (inactive) tFUS.

Participant Groups

Group I: Group Receiving Active Stimulation and Sham Stimulation on Separate Days (All Participants) Experimental Treatment 2 Interventions

All participants will receive active stimulation and non-active (sham) stimulation on different days. Before the stimulation sessions, all participants will complete experimental tasks during functional magnetic resonance imaging. On the next two study days, all participants will complete tasks before and after receiving active transcranial focused ultrasound (tFUS) on one day and sham (non-active) tFUS on another day. Stimulation (active or sham) is conducted briefly (\< 10 minutes) in between tasks, not during tasks.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Findings from Research

MR-guided focused ultrasound (MRgFUS) shows promise in treating neuropsychiatric disorders like obsessive-compulsive disorder (OCD) and depression, with preliminary studies indicating improvements in symptoms, although more rigorous trials are needed.

Low-intensity MRgFUS may help open the blood-brain barrier and modulate brain activity, but current evidence is limited, necessitating further comparative studies to evaluate its effectiveness against other treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incisionless MR-guided focused ultrasound: technical considerations and current therapeutic approaches in psychiatric disorders. Kinfe, T., Stadlbauer, A., Winder, K., et al.[2021]

Magnetic-resonance-guided focused ultrasound (MRgFUS) is a noninvasive and effective treatment for symptomatic uterine fibroids, preserving the uterus while alleviating symptoms.

The review highlights the importance of understanding MRgFUS technology, patient selection, and outcomes, as well as its potential impact on fertility, which is crucial for interventional radiologists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updates on MR-Guided Focused Ultrasound for Symptomatic Uterine Fibroids. Sridhar, D., Kohi, MP.[2020]

The second-generation MRgFUS system significantly improved treatment outcomes for uterine fibroids, achieving higher nonperfused volume ratios compared to the first-generation system, indicating better efficacy in ablation.

Since the introduction of the second-generation system, there have been no major adverse events or hospital admissions, highlighting enhanced patient safety during MRgFUS treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Clinical Performance Between Two Generations of Magnetic Resonance-guided Focused Ultrasound Systems in Treatments of Uterine Leiomyomas. Browne, JE., Gorny, KR., Hangiandreou, NJ., et al.[2021]

Focused ultrasound surgery (FUS) is a noninvasive treatment that effectively destroys targeted tissues while protecting surrounding areas, making it a safe option for patients.

When combined with magnetic resonance guidance (MRgFUS), this technique allows for real-time monitoring and personalized treatment, showing promising results in conditions like uterine fibroids and potential applications in prostate and liver tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ExAblate magnetic resonance-guided focused ultrasound system in multiple body applications. Dick, EA., Gedroyc, WM.[2010]

Magnetic Resonance-guided Focused Ultrasound (MRgFUS) shows promise as an effective treatment for refractory neuropathic pain, with studies involving 66 patients indicating variable degrees of pain improvement.

The safety profile of MRgFUS is favorable, with only mild and transient adverse events reported, and a major adverse event (intracerebral bleeding) occurring in just one case, suggesting it is a relatively safe option for patients with chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-guided Focused Ultrasound thalamotomy for refractory neuropathic pain: a systematic review and critical appraisal of current knowledge. Taranta, V., Saporito, G., Ornello, R., 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]

A systematic review of 33 studies on low-intensity transcranial focused ultrasound stimulation (TFUS) indicates that adverse effects are very rare, with most studies showing no significant negative outcomes even when safety limits were exceeded.

However, at high stimulation intensities, TFUS can potentially cause serious issues like hemorrhage, cell death, and unintended blood-brain barrier opening, highlighting the need for further research to establish clear safety guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. Pasquinelli, C., Hanson, LG., Siebner, HR., et al.[2020]

Transcranial focused ultrasound (tFUS) can selectively target and modulate deep brain structures, such as the amygdala and entorhinal cortex, in healthy adults, leading to significant changes in brain perfusion and activity.

The study demonstrated that tFUS does not activate the auditory cortex, indicating that its effects are due to direct neuromodulation rather than an acoustic response, suggesting potential therapeutic applications for neurological and psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans. Kuhn, T., Spivak, NM., Dang, BH., et al.[2023]

Magnetic resonance-guided focused ultrasound (MRgFUS) is a safe and effective incisionless treatment for centrally located brain lesions in adolescents and young adults, with no complications reported in a study of 5 patients aged 15-22.

The procedure successfully achieved thermoablation in 4 out of 5 cases, leading to improvements in symptoms such as seizure control, demonstrating its potential therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. Tierney, TS., Alavian, KN., Altman, N., et al.[2022]

The study evaluated different MR coils for use in MRI-guided Focused Ultrasound Surgery (MRgFUS) for liver tumors, finding that single-loop four-channel Duoflex and Gem coils provided reliable thermal readings and signal quality during dynamic tracking.

Body array coils were found to be unsuitable for liver MRgFUS due to significant signal loss, suggesting that specialized coil designs are necessary for effective treatment in dynamic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-guided focused ultrasound application for moving target tumor ablation in abdominal area: coil selection. Mihcin, S., Gagliardo, C., Toia, P., et al.[2021]

High-intensity focused ultrasound (HIFU) guided by MRI is a non-invasive method that allows for precise thermal ablation of target tissues while protecting surrounding organs, enhancing the safety of the procedure.

MRgFUS is clinically established for treating symptomatic uterine fibroids and shows promising results for various conditions, including palliative care for bone metastases and treatment of tumors in the prostate, breast, liver, and brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[MR-guided focused ultrasound. Current and future applications]. Trumm, CG., Napoli, A., Peller, M., et al.[2022]

Focused ultrasound is a noninvasive brain stimulation technique that offers precise targeting, combining benefits from both repetitive transcranial magnetic stimulation and deep brain stimulation.

High-intensity focused ultrasound is already being used in incisionless surgeries, such as capsulotomies for treating obsessive-compulsive disorder, showcasing its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound as a Neurotherapeutic: A Circuit- and System-Based Interrogation. Spivak, NM., Tyler, WJ., Bari, AA., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Incisionless MR-guided focused ultrasound: technical considerations and current therapeutic approaches in psychiatric disorders. [2021]

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

Updates on MR-Guided Focused Ultrasound for Symptomatic Uterine Fibroids. [2020]

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

Comparison of Clinical Performance Between Two Generations of Magnetic Resonance-guided Focused Ultrasound Systems in Treatments of Uterine Leiomyomas. [2021]

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

ExAblate magnetic resonance-guided focused ultrasound system in multiple body applications. [2010]

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

Magnetic Resonance-guided Focused Ultrasound thalamotomy for refractory neuropathic pain: a systematic review and critical appraisal of current knowledge. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans. [2023]

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

Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. [2022]

10. England pubmed.ncbi.nlm.nih.gov

MR-guided focused ultrasound application for moving target tumor ablation in abdominal area: coil selection. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

[MR-guided focused ultrasound. Current and future applications]. [2022]

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

Ultrasound as a Neurotherapeutic: A Circuit- and System-Based Interrogation. [2023]