Transcranial Ultrasound + Propofol for Healthy Subjects

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Stanford University

Must not be taking: Opioids, Naltrexone, Clonidine, others

Disqualifiers: Neurological, Cardiovascular, Pulmonary, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if focused ultrasound on the brain alters the effects of the anesthetic propofol and to ensure the safety and practicality of this combination. Researchers will compare focused ultrasound with a non-targeted version while participants receive propofol, observing brain signals and behavior. Ideal participants are healthy individuals without complex medical conditions who are comfortable undergoing MRI scans and anesthesia sessions. As a Phase 4 trial, this research helps clarify how the already FDA-approved treatment benefits more patients.

Do I need to stop taking my current medications for the trial?

Yes, you will need to stop taking certain medications, specifically opioids, opioid antagonists like naltrexone, and clonidine, as they are listed in the exclusion criteria.

What is the safety track record for low-intensity transcranial ultrasound and propofol?

Research has shown that low-intensity transcranial ultrasound is generally safe and easy for people to handle. This type of ultrasound, which can affect brain activity, has few side effects. Participants in earlier studies reported only minor negative symptoms, and tests confirmed its safety for humans.

Propofol, a widely used anesthetic, has received FDA approval for many uses, indicating its general safety. Most people tolerate it well, but like all anesthetics, it can cause side effects such as low blood pressure or changes in breathing.

In summary, past studies have demonstrated the safety of both low-intensity transcranial ultrasound and propofol. They are usually well-tolerated, but, as with any treatment, some risks may still exist. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores a novel combination of low-intensity transcranial ultrasound and Propofol, which could offer new insights into brain function and consciousness. Unlike traditional brain imaging or stimulation techniques, this approach uses focused ultrasound to non-invasively target specific brain areas, potentially leading to more precise interventions. Additionally, the trial investigates the effects of ultrasound in combination with Propofol, a commonly used anesthetic, which might reveal new ways to enhance or modulate its effects on the brain. This could pave the way for breakthroughs in understanding and potentially treating conditions related to brain activity.

What evidence suggests that this trial's treatments could be effective?

Research has shown that low-intensity transcranial ultrasound (LITUS) can help treat various conditions. It assists with brain and mental health issues, as well as pain and sleep problems. Studies suggest that LITUS can change brain activity, potentially improving symptoms in these areas. In this trial, participants will experience both active and sham LITUS to assess its effects. Propofol, a well-known drug, helps people sleep during medical procedures. This trial examines how LITUS might affect or enhance propofol's effects on the brain. The goal is to discover new insights into brain function and find new treatment options. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for healthy individuals interested in participating in a study to understand how ultrasound affects the brain under anesthesia. Participants will undergo MRI scans, receive two types of ultrasound sessions (one focused and one sham), and have propofol anesthesia administered twice.

Inclusion Criteria

Body mass index between 17-35 kg/m2

Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information

I am between 18 and 65 years old.

Exclusion Criteria

Any other clinically significant abnormal laboratory result at the time of the screening exam

Any other clinically significant physical exam abnormality on the screening physical examination

Participation in any clinical trial with an investigational drug or device that conflicts with this trial, within the past month or concurrent to study participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

MRI Scan

Participants obtain one non-contrast MRI scan of the brain

1 day

1 visit (in-person)

Ultrasound and Anesthesia Sessions

Participants receive two separate sessions of ultrasound to the brain (one focused and one sham) and undergo two separate sessions of propofol anesthesia

2 sessions with a washout period of 5 days or greater between sessions

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low-intensity transcranial ultrasound
• Propofol

Trial Overview The study is testing whether low-intensity transcranial focused ultrasound can influence the effects or potency of an anesthetic drug called propofol. It involves comparing active ultrasound with non-targeted sham ultrasound while participants are sedated with propofol.

How Is the Trial Designed?

Group I: Sham then Active Experimental Treatment 2 Interventions

Sham (unfocused) ultrasound followed by washout of 5 days or greater, followed by active (focused) ultrasound

Group II: Active then Sham Experimental Treatment 2 Interventions

Active (focused) ultrasound followed by washout of 5 days or greater, followed by sham (unfocused) ultrasound

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12281706/

The efficacy and mechanisms of low-intensity transcranial ... Current research indicates that LITUS targeting various brain regions, including IC, THAL, S1, ACC, and PAG could improve various pain metrics.

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 ... We observed a significant reduction on our primary outcome, a general measure of negative affect symptoms in MATRDs. The effect was ...

4. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2019.00696/full

Brain Modulatory Effects by Low-Intensity Transcranial ... Focused ultrasound is promising for transcranial neuromodulation because it has less energy aberration. Unfocused ultrasound is typically used ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/02656736.2025.2539986

Strengths and weaknesses of transcranial ultrasound ... Abstract. This article reviews early studies that have demonstrated the ability of low intensity ultrasound waves to modulate brain activity.

6. 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 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25003535

ITRUSST Consensus on Biophysical Safety for ... Protocols exceeding these levels are not necessarily unsafe or significant risk. Further data is needed to establish the threshold for ...

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

A retrospective qualitative report of symptoms and safety ... We provide an evaluation of the safety of LIFU for human neuromodulation through participant report and neurological assessment with a comparison of ...

9. e-bnr.org e-bnr.org/Synapse/Data/PDFData/0176BN/bn-14-e4.pdf

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- ...

10. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-025-02096-y

The efficacy and mechanisms of low-intensity transcranial ... Most included studies showed positive effects and verified the safety of LITUS on pain, reporting few adverse effects. Conclusions. LITUS is an ...