Transcranial Focused Ultrasound Safety in Healthy Subjects

Overseen By Lisa M McTeague, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Psychotropics, Stimulants, Steroids, others

Disqualifiers: Psychiatric diagnosis, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the safety and effectiveness of a new technique called Transcranial Focused Ultrasound (tFUS) to study brain activity. The researchers focus on how this technique can safely influence the Central Medial Thalamus, a part of the brain involved in sleep, without affecting other areas. Participants will receive different frequencies of ultrasound to observe its impact on brain function. Individuals who are generally healthy, without a history of mental or physical illness, and have no implanted metal may be suitable for this trial. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research in brain activity and sleep.

Will I have to stop taking my current medications?

The trial requires that you stop taking any psychotropic medications (drugs that affect your mood, thoughts, or behavior) at least 5 half-lives (the time it takes for the drug's active substance to reduce by half in your body) before the procedure. Additionally, you cannot be taking medications like stimulants, modafinil, thyroid medication, or steroids.

What prior data suggests that this technique is safe for studying brain function?

Research has shown that transcranial focused ultrasound (tFUS) is generally safe for people. Studies indicate that using low sound levels can alter activity in specific brain areas without major issues. One study suggested that tFUS is a promising and safe method to influence brain activity without surgery.

A review of past cases where tFUS altered brain activity supports its safety, noting that side effects are usually mild. Additionally, low-intensity tFUS has effectively treated conditions like sleep problems and pain, further supporting its safe use in these areas.

Overall, while researchers continue to study tFUS, current research suggests it is safe for people, especially at low intensities. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcranial focused ultrasound because it offers a non-invasive way to potentially modulate brain activity. Unlike traditional treatments like drugs or surgery, this technique uses sound waves to target specific areas of the brain without needing to cut into the body or administer medication. This could mean fewer side effects and more precise treatment. The variation in frequency—low, medium, and high—allows researchers to explore which intensity best influences brain function, paving the way for personalized therapies.

What evidence suggests that Transcranial Focused Ultrasound is effective for brain modulation?

Research has shown that transcranial focused ultrasound (tFUS) could be a promising treatment for various brain-related conditions. Studies have found it may help with neurological and psychiatric disorders, pain, sleep problems, and even high blood pressure. This technique sends gentle ultrasound waves into the brain, targeting deep areas. It can change brain activity without surgery. Early results suggest it might be effective and safe for conditions like depression and pain by affecting specific brain circuits. Overall, tFUS appears to be a non-invasive way to treat and study brain function. This trial will test different frequencies of tFUS to evaluate their safety in healthy subjects. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 22-55 who speak English, can consent, and have no history of mental or physical illness. Women must not be pregnant and participants should not have metal implants. All must commit to the study schedule.

Inclusion Criteria

I am able to understand and agree to the study's requirements.

English as a primary language

Willingness to adhere to the tFUS study schedule and assessments

Exclusion Criteria

Implanted devices/ferrous metal of any kind

I cannot complete tests that measure my thinking skills.

I have no history of major brain disorders or injuries.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive focused ultrasound stimulation using the Attune ATTN201 device over the course of 1 month

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including EEG recordings and behavioral assessments

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Focused Ultrasound

Trial Overview The study tests a device called Attune ATTN201 using Transcranial Focused Ultrasound (tFUS) on the Central Medial Thalamus in the brain to see how it affects sleep induction and brain activity without harming surrounding tissue.

How Is the Trial Designed?

Group I: Focused Ultrasound Dose #8 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using high frequency stimulation as condition 4. Stimulation will last 1-10 minutes.

Group II: Focused Ultrasound Dose #7 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using medium frequency stimulation as condition 4. Stimulation will last 1-10 minutes.

Group III: Focused Ultrasound Dose #6 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using low frequency stimulation as condition 4. Stimulation will last 1-10 minutes.

Group IV: Focused Ultrasound Dose #3 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using low frequency stimulation as condition 4. Stimulation will last 1-10 minutes.

Group V: Focused Ultrasound Dose #2 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using medium frequency stimulation as condition 2. Stimulation will last 1-10 minutes.

Group VI: Focused Ultrasound Dose #1 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using high frequency stimulation as condition 1. Stimulation will last 1-10 minutes.

Group VII: Focused Ultrasound Dose #5 Placebo Group 1 Intervention

Focused Ultrasound will be administered using the sham condition.

Group VIII: Focused Ultrasound Dose #4 Placebo Group 1 Intervention

Focused Ultrasound will be administered using the sham condition.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Attune Neurosciences

Collaborator

Trials

1

Recruited

30+

Attune Neurosciences Inc

Industry Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

A 63-year-old patient with a recurrent glioblastoma underwent transcranial MR-guided focused ultrasound surgery (MRgFUS), demonstrating the feasibility of this noninvasive technique for brain tumor ablation.

The procedure involved 25 high-power sonications and successfully achieved partial tumor ablation without causing neurological deficits or adverse effects, highlighting its safety and potential for treating brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound. Coluccia, D., Fandino, J., Schwyzer, L., et al.[2020]

Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive technique that can precisely target and treat brain disorders by creating thermal lesions and disrupting the blood-brain barrier, which is a significant advancement in neurotherapeutics.

MRgFUS has been successfully used in various clinical applications, including treating bone metastases and uterine fibroids, and is being explored as a safer alternative to traditional neurosurgery for a range of brain-related conditions, supported by studies from small animal models to large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. Lipsman, N., Mainprize, TG., Schwartz, ML., et al.[2021]

In a study involving 30 women with breast cancer, MRgFUS treatment resulted in an impressive average of 96.9% tumor necrosis, indicating its high effectiveness in ablating breast carcinomas.

The procedure was well tolerated with minimal adverse effects, especially when performed under local anesthesia, suggesting it could be a safe noninvasive alternative to traditional surgical methods like lumpectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness. Furusawa, H., Namba, K., Thomsen, S., et al.[2022]

Transcranial MR-guided Focused Ultrasound Surgery (MRgFUS) has shown promising results in treating conditions like neuropathic pain and essential tremor, with most patients experiencing significant symptom improvement after treatment.

Despite its potential, there are safety concerns, as serious adverse effects, including intracranial hemorrhages, were reported in two cases due to cavitation during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive transcranial brain ablation with high-intensity focused ultrasound. Jenne, JW.[2014]

The dual-channel radiofrequency receive-only head coil significantly improves imaging quality in tcMRgFUS, providing up to 4 times better signal-to-noise ratio (SNR) compared to the standard body coil, which enhances visualization of critical brain structures.

The head coil also improves MR thermometry accuracy, reducing temperature uncertainty from 0.96°C to 0.41°C, allowing for more precise monitoring of thermal ablation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an MRI receive head coil for use in transcranial MR guided focused ultrasound for functional neurosurgery. Bitton, RR., Sheingaouz, E., Assif, B., et al.[2021]

The study presents a validated, open-source MR-guided focused ultrasound (MRgFUS) system that allows for precise and controllable thermal and mechanical treatments in small animals, which could enhance research in various medical applications.

This system has been successfully tested in tissue-mimicking phantoms and live mice, demonstrating accurate temperature control and effective treatment delivery, making it a cost-effective option for researchers interested in MRgFUS technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-source, small-animal magnetic resonance-guided focused ultrasound system. Poorman, ME., Chaplin, VL., Wilkens, K., 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]

The study demonstrated that enhanced magnetic resonance-guided focused ultrasound (MRgFUS) can create ablations that are, on average, 1.8 times larger than those produced by standard sonication using the same energy, indicating improved efficacy.

The enhanced MRgFUS method was found to be safe and controllable, with predictable ablation locations and consistent thermal damage patterns, suggesting it could significantly shorten tumor ablation procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery using an enhanced sonication technique in a pig muscle model. Kopelman, D., Inbar, Y., Hanannel, A., et al.[2019]

MR-guided focused ultrasound (MRgFUS) is a promising non-invasive technique for treating deep brain conditions, showing effectiveness in chronic diseases like Parkinson's and essential tremor, as well as in neuropathic pain.

The method is advantageous because it does not require anesthesia, avoids ionizing radiation, and has low complication rates, making it a safer alternative to traditional neurosurgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-guided focused ultrasound: a new generation treatment of Parkinson's disease, essential tremor and neuropathic pain. Dobrakowski, PP., Machowska-Majchrzak, AK., Labuz-Roszak, B., et al.[2021]

Transcranial MR-guided focused ultrasound (MRgFUS) is an innovative, non-invasive technique that can effectively treat movement disorders like essential tremor through thermoablation, eliminating the need for open surgery.

The technology is also being explored for its ability to open the blood-brain barrier using microbubbles, which could enhance targeted drug delivery to the brain, potentially improving treatment options for various neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical Principles and Clinical Workflow of Transcranial MR-Guided Focused Ultrasound. Meng, Y., Jones, RM., Davidson, B., et al.[2021]

Magnetic resonance-guided focused ultrasound (MRgFUS) therapy for uterine fibroids has a relatively low incidence of serious complications, with major adverse events occurring in only 0.41% of cases across 43 studies analyzed.

The most common adverse events reported include pain, skin burns, urinary tract infections, and sciatic neuropraxia, with an overall adverse event occurrence rate of 24.67%, indicating that while MRgFUS is generally safe, some side effects do occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and complications after magnetic resonance-guided focused ultrasound (MRgFUS) therapy in uterine fibroids - a systematic review and future perspectives. Kociuba, J., Łoziński, T., Zgliczyńska, M., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8507972/

Transcranial Focused Ultrasound Neuromodulation: A Review ... Transcranial focused ultrasound (tFUS) transmits low-intensity ultrasound into the brain non-invasively and focuses on deep brain regions. It is an emerging ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149763423004700

The effectiveness and safety of low-intensity transcranial ... LITUS demonstrated therapeutic efficacy in neurological disorders, psychiatric disorders, pain, sleep disorders and hypertension.

3. nature.com nature.com/articles/s41380-025-03033-w

Low-intensity transcranial focused ultrasound amygdala ... tFUS is a non-invasive technique for direct subcortical neuromodulation, but its safety, feasibility, and promise as a potential treatment is largely unknown.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11321877/

Effect of Low-Intensity Transcranial Focused Ultrasound ... The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder.

5. ashpublications.org ashpublications.org/blood/article/144/10/1101/516866/Low-intensity-transcranial-focused-ultrasound

Low-intensity transcranial focused ultrasound suppresses ... Low-intensity transcranial focused ultrasound suppresses pain by modulating pain-processing brain circuits.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9879416/

Safety Review and Perspectives of Transcranial Focused ... Transcranial focused ultrasound (tFUS) given at a low acoustic intensity has been shown to increase or suppress the excitability of region-specific brain areas.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X19303389

Safety of transcranial focused ultrasound stimulation The review covers the mechanisms-of-action by which TFUS may cause adverse effects and the available data on the possible occurrence of such effects in animal ...

8. nature.com nature.com/articles/s41598-020-62265-8

A retrospective qualitative report of symptoms and safety ... A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans. Wynn Legon,; Sarah ...

9. 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 ...