Focused Ultrasound for Healthy Subjects

Overseen By Kevin A Caulfield

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Psychotropic medications

Disqualifiers: Neurological illness, Substance abuse, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 3 sessions

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how focused ultrasound stimulation affects brain activity, specifically examining motor responses and certain brain chemicals. Participants are divided into three treatment groups: one with more intense stimulation, one with less intense stimulation, and a sham group that receives no real stimulation. The trial seeks healthy individuals aged 18-55 without a history of neurological or mental health issues who can comfortably undergo MRI scans. As an unphased trial, it offers participants a unique opportunity to contribute to groundbreaking research in brain stimulation.

Will I have to stop taking my current medications?

If you are taking any psychotropic medications (drugs that affect your mind, emotions, or behavior), you will need to stop taking them at least 5 half-lives (a period of time it takes for the drug's active substance to reduce by half in the body) before the procedure. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What prior data suggests that Focused Ultrasound Stimulation is safe for healthy subjects?

Research has shown that transcranial focused ultrasound stimulation (tFUS) can be safe at low levels. When applied carefully, tFUS can alter brain activity without harm. Some studies have reported minor side effects, such as headaches in about 4% of participants and a feeling of pressure on the head in about 17%. Other possible effects include mood changes in 3% and some pain in 8% of participants.

These effects are usually mild. Serious issues like bleeding or brain cell damage are associated with high intensity or frequency, which are uncommon in controlled trials. The trial under consideration is designed to ensure participant safety by using low-intensity ultrasound. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial of Focused Ultrasound Stimulation because it offers a non-invasive way to potentially enhance or suppress motor evoked potentials in the brain. Unlike traditional treatments that may involve medication or surgical interventions, this technique uses sound waves to target specific areas of the brain, offering a new level of precision. The trial examines two experimental protocols: one with excitatory parameters operating at a 50% duty cycle and another with inhibitory parameters at a 5% duty cycle. The precision and non-invasiveness of focused ultrasound could lead to breakthroughs in how we modulate brain activity safely and effectively.

What evidence suggests that this trial's treatments could be effective for Motor Evoked Potentials?

Research shows that Focused Ultrasound Stimulation (tFUS) can alter brain activity by targeting specific areas. This trial will divide participants into different arms to study these effects. In the excitatory approach, which one arm will receive, studies have found that tFUS can reliably cause movement responses in both animals and humans, with success rates between 70% and 100% under optimal conditions. This method uses a 50% duty cycle to enhance motor functions. Conversely, another arm will receive the inhibitory approach, which uses a 5% duty cycle and has weakened motor signals in the brain. This reduction in certain brain activities might help with conditions characterized by excessive activity. Both methods have demonstrated clear effects on the brain, making tFUS a promising tool for modifying brain function. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for healthy men and women aged 18-55 who speak English as their primary language. Participants must not be pregnant, have no history of mental or physical illness, no metal implants, and cannot have a personal or family history of seizures or epilepsy. They should not be on psychotropic medications recently nor have any substance abuse issues.

Inclusion Criteria

I am in good health with no history of serious illness or metal implants.

English as a primary language

Willingness to adhere to the tFUS and MRI study schedule

Exclusion Criteria

I or someone in my family has had a neurological illness or injury.

Hair in dreadlocks, braids, or weave

I have taken mental health medication within a certain time before the procedure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive three sessions of Focused Ultrasound Stimulation to their motor hotspot with different parameters

3 sessions

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Immediate Post-Stimulation

What Are the Treatments Tested in This Trial?

Interventions

• Focused Ultrasound Stimulation

Trial Overview The study is examining the safety and effects of Transcranial Focused Ultrasound (tFUS) on motor functions by measuring Motor Evoked Potentials (MEPs) and monitoring GABA and Glutamate concentrations in the brain among healthy individuals.

How Is the Trial Designed?

Group I: Inhibitory tFUS parameters effect of Motor Evoked Potentials Experimental Treatment 1 Intervention

All participants will receive three sessions of Focused Ultrasound Stimulation to their motor hotspot. This stimulation cycle will operate at a 5% duty cycle

Group II: Excitatory tFUS parameters effect on Motor Evoked Potentials Experimental Treatment 1 Intervention

All participants will receive three sessions of Focused Ultrasound Stimulation to their motor hotspot. This stimulation cycle will operate at a 50% duty cycle.

Group III: Sham tFUS parameters effect of Motor Evoked Potentials Placebo Group 1 Intervention

All participants will receive three sessions of Focused Ultrasound Stimulation to their motor hotspot. This stimulation cycle will utilize an air-filled spacer to block stimulation from reaching the brain

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

BRAINBox Solutions Inc

Industry Sponsor

Trials

2

Recruited

2,000+

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]

Pulsed focused ultrasound can effectively stimulate nerve structures and neurons, showing potential for various medical applications, including diagnosing neurological diseases and assessing skin and tissue sensitivity.

This technique may also aid in diagnosing hearing disorders and providing auditory information to individuals with specific types of hearing loss, highlighting its versatility in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of focused ultrasound for stimulation of nerve structures. Gavrilov, LR.[2019]

Transcranial focused ultrasound (tFUS) can precisely target specific brain areas with low acoustic intensity, effectively modulating brain excitability and potentially promoting neural plasticity for neurorehabilitation.

The review highlights the excellent safety profile of tFUS, but emphasizes the need for new safety guidelines and recommendations for its use in healthy volunteers and clinical settings, based on a comprehensive analysis of acoustic parameters and their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation. Lee, W., Weisholtz, DS., Strangman, GE., et al.[2023]

A study involving 120 participants evaluated the safety of low intensity transcranial focused ultrasound (LIFU) for neuromodulation, finding no serious adverse effects and only mild to moderate symptoms reported by 7 participants, which were generally transient.

The symptom profile from LIFU was similar to other non-invasive brain stimulation methods, suggesting that LIFU is a safe option for neuromodulation with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans. Legon, W., Adams, S., Bansal, P., et al.[2021]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05792020

Study Details | NCT05792020 | Safety, Parameterization ... This aim will test whether motor tFUS parameters thought to be excitatory (50% duty cycle) vs. inhibitory (5% duty cycle) elicit their predicted effects on MEPs ...

3. jneuroengrehab.biomedcentral.com jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-025-01753-2

A panoramic review of transcranial focused ultrasound ... In rodent studies, tFUS can reliably elicit motor responses at frequencies below 1 MHz, with success rates reaching 70–100% under optimal ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X2200081X

Human Studies of Transcranial Ultrasound neuromodulation The aim of this work is to review human studies with an emphasis on TUS devices, sonication parameters, outcome measures, results, and adverse effects.

5. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2021.749162/full

Transcranial Focused Ultrasound Neuromodulation Studies using various parameters have shown that tFUS can modulate neural activity in the brains of animals and humans. It has the potential to modulate brain ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31401074/

Safety of transcranial focused ultrasound stimulation At high stimulation intensity and/or rate, TFUS may cause haemorrhage, cell death or damage, and unintentional blood-brain barrier (BBB) opening. TFUS may also ...

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

Safety of transcranial focused ultrasound stimulation At high stimulation intensity and/or rate, TFUS may cause haemorrhage, cell death or damage, and unintentional blood-brain barrier (BBB) opening. TFUS may also ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9599299/

Safety of Clinical Ultrasound Neuromodulation - PMC Minor adverse events were noted with free reporting, namely headache (4%), mood deterioration (3%), pain (8%) and painless pressure sensations (17%) [57].

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

A retrospective qualitative report of symptoms and safety ... Data from all seven experiments revealed 7/64 reported mild or moderate symptoms that they felt were 'possible' or 'probably' related to the ...

10. 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.