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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators goal is to target FUS energy to the centromedian nucleus of the thalamus (CMT), the core of arousal, which is inaccessible by traditional non-invasive neuromodulation devices. The CMT is an ideal stimulation target for augmenting alertness, as it is intimately linked with the cortex through the well described thalamocortical circuit to entrain network oscillations.

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 data supports the effectiveness of the treatment Transcranial Focused Ultrasound (tFUS) for alertness?

Transcranial focused ultrasound (tFUS) is a promising non-invasive technology that can modulate brain activity with high precision, as shown in studies where it affects brain areas related to movement and brain signals. Additionally, MR-guided focused ultrasound (MRgFUS) has been effective in treating other conditions like uterine fibroids, suggesting potential for broader applications. ^{1 2 3 4 5}

Is focused ultrasound generally safe for humans?

Focused ultrasound, including types like MRgFUS and HIFU, is generally considered safe for treating conditions like uterine fibroids, with most side effects being mild and temporary, such as tenderness and redness. Rarely, more serious effects like nerve-related issues can occur, often due to improper technique. ^{3 6 7 8 9}

How is the treatment Transcranial Focused Ultrasound (tFUS) unique for improving alertness?

Transcranial Focused Ultrasound (tFUS) is unique because it is a non-surgical treatment that can precisely target specific areas of the brain with high spatial resolution, unlike other technologies that may affect larger areas. This allows for more accurate modulation of brain activity, potentially improving alertness without invasive procedures. ^{3 4 7 10 11}

Eligibility Criteria

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

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

Implanted devices/ferrous metal of any kind

Inability to adhere to the treatment schedule

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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]

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]

References

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

Comparison of Transcranial Focused Ultrasound and Transcranial Pulse Stimulation for Neuromodulation: A Computational Study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Update in the clinical application of focused ultrasound. [2022]

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

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

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

Transcranial focused ultrasound for BOLD fMRI signal modulation in humans. [2022]

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

Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex. [2023]

6. England 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. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

MR-Guided Focused Ultrasound in Fibroid Treatment - Results of the 4th Radiological-Gynecological Expert Meeting. [2019]

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

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

9. 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]

10. Ireland pubmed.ncbi.nlm.nih.gov

Methodology on quantification of sonication duration for safe application of MR guided focused ultrasound for liver tumour ablation. [2018]

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

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