Focused Ultrasound for Alertness

Overseen By Jacob D Weaver, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

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: 1-10 minutes per session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how transcranial focused ultrasound, a non-invasive treatment, can improve alertness by targeting the centromedian nucleus of the thalamus, a brain area crucial for wakefulness. Participants will undergo one of several ultrasound sessions, each with different frequencies, to determine the most effective. The trial seeks healthy individuals aged 22 to 55, with no history of mental or physical illness, who can commit to the study schedule. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

The trial requires that you stop taking any psychotropic medications (drugs that affect mood, perception, or behavior) at least 5 half-lives (a measure of time it takes for the drug's concentration to reduce by half) before the procedure. Additionally, you cannot participate if you are taking medications like stimulants, modafinil, thyroid medication, or steroids.

What prior data suggests that transcranial focused ultrasound is safe for augmenting alertness?

Research has shown that transcranial focused ultrasound (TFUS) is usually well-tolerated as a non-invasive brain treatment. Studies have found that side effects are rare. Although higher levels might pose risks such as cell damage or bleeding, these occurrences are uncommon. Most uses of TFUS, particularly at lower levels, seem to safely stimulate brain activity without surgery. This makes it a good option for exploring brain functions safely. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about transcranial focused ultrasound for improving alertness because it offers a non-invasive approach utilizing sound waves to stimulate the brain. Unlike typical treatments for alertness, which often involve medications or behavioral techniques, this method uses high, medium, or low frequency ultrasound waves to directly engage brain activity. The potential for quick, effective stimulation lasting only 1 to 10 minutes sets this apart from traditional treatments, which can take longer to show results. Plus, the use of different frequencies allows for tailored approaches, potentially increasing its effectiveness and minimizing side effects compared to current options.

What evidence suggests that transcranial focused ultrasound is effective for enhancing alertness?

Research has shown that transcranial focused ultrasound (tFUS) can directly influence brain regions controlling alertness. Studies with animals and humans have demonstrated that tFUS can either increase or decrease brain activity, depending on its application. This non-invasive technology, which does not involve surgery, offers a safer option compared to other treatments. Although most research remains in the early stages, initial findings suggest that tFUS can effectively alter brain activity by targeting specific areas related to alertness. This trial will explore different doses of tFUS, including high, medium, and low frequency stimulations, as well as a sham condition, to assess its potential as a tool for enhancing alertness by stimulating the centromedian nucleus of the thalamus, a crucial area for maintaining wakefulness and alertness. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals who are interested in improving their reaction time and alertness. Specific eligibility criteria details were not provided, so it's best to contact the study organizers for more information on who can participate.

Inclusion Criteria

English is my first or primary fluent language.

Able to read consent document and provide informed consent

I am in good health with no history of serious mental or physical illness.

Exclusion Criteria

Implanted devices/ferrous metal of any kind

Pregnancy (or suspected/possible pregnancy or plan to become pregnant in the short term)

Inability to adhere to the treatment schedule

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 targeting the centromedian nucleus of the thalamus using various frequency conditions

1-10 minutes per session

Multiple sessions (in-person)

Follow-up

Participants are monitored for changes in EEG and reaction time over a 2-year period

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Focused Ultrasound

Trial Overview The trial is testing Transcranial Focused Ultrasound (tFUS) aimed at the centromedian nucleus of the thalamus, a brain area linked with arousal and attention, to see if it can enhance alertness and performance.

How Is the Trial Designed?

Group I: 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 II: 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 III: 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 IV: 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 Inc

Industry Sponsor

Trials

1

Recruited

30+

Nano-Bio Materials Consortium

Collaborator

Published Research Related to This Trial

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]

Transcranial focus ultrasound stimulation (tFUS) can significantly modulate excitability in the human motor cortex, with different parameters leading to either increased or decreased excitability, as shown in a study involving 10 subjects.

The study revealed that tFUS affects neurotransmitter levels, decreasing GABA and increasing glutamate concentrations, which suggests it alters the balance of excitatory and inhibitory signals in the brain, potentially impacting motor function and plasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex. Zhang, T., Guo, B., Zuo, Z., et al.[2023]

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]

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]

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]

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]

Transcranial MRI-guided focused ultrasound (MRgFUS) is an established therapy for treating essential and parkinsonian tremors, showing long-term safety and efficacy in recent studies.

The technique is expanding beyond tremors to include new indications like focal dystonia and neuropsychiatric conditions, with promising preliminary results, and it also allows for innovative applications such as opening the blood-brain barrier and neuromodulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update in the clinical application of focused ultrasound. Natera-Villalba, E., Matarazzo, M., Martinez-Fernandez, R.[2022]

Transcranial focused ultrasound (tFUS) is a promising non-surgical technique for neuromodulation that offers better spatial resolution compared to traditional electro and electromagnetic methods.

tFUS can effectively target sub-cortical brain structures non-invasively, and its combination with BOLD functional MRI allows for enhanced examination of brain activity in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound for BOLD fMRI signal modulation in humans. Leo Ai, ., Mueller, JK., Grant, A., et al.[2022]

The novel TRANS-FUSIMO Treatment System (TTS) successfully quantifies key parameters for liver tumor ablation using Magnetic Resonance Guided Focused Ultrasound (MRgFUS), achieving a maximum deviation of only 0.16 seconds from planned sonication duration, which is crucial for safe and effective treatment.

The study demonstrated that the sonication process is consistent across different operators, indicating reliability in the system's performance, which is essential for clinical applications and quality assurance in medical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodology on quantification of sonication duration for safe application of MR guided focused ultrasound for liver tumour ablation. Mihcin, S., Karakitsios, I., Le, N., et al.[2018]

Citations

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

Transcranial Focused Ultrasound Neuromodulation: A Review ... This review synthesizes animal and human research outcomes and offers an integrated description of the excitatory and inhibitory effects of tFUS.

2. 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, ...

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. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?lcdid=37738&ver=22

Magnetic-Resonance-Guided Focused Ultrasound Surgery ... The authors conclude that “MRgFUS is a promising therapy with the potential to replace DBS for patients who cannot tolerate DBS, the standard surgical treatment ...

5. probiologists.com probiologists.com/article/focused-ultrasound-innovation-in-use-for-neurologic-conditions

Focused ultrasound: Innovation in use for neurologic ... Focused ultrasound has emerged as a key tool for neurologic disorders. In this focused review, we discuss the utility in disrupting the blood brain barrier ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6579808/

Transcranial Focused Ultrasound (tFUS ... - PubMed Central Transcranial focused ultrasound is an emerging technique for non-invasive neurostimulation. Compared to magnetic or electric non-invasive brain stimulation,

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

Safety of transcranial focused ultrasound stimulation Adverse effects of TFUS were very rare. At high stimulation intensity and/or rate, TFUS may cause haemorrhage, cell death or damage, and unintentional blood- ...

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

A retrospective qualitative report of symptoms and safety ... Transcranial focused ultrasound (LIFU) is a new and promising non-surgical low-energy technique that uses mechanical energy to modulate neuronal ...

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 ...