Ultrasonic Brain Stimulation for Depression

Overseen By Angela Valentina Bisconti

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Brian Mickey

Disqualifiers: Neurologic disorder, Pregnancy, Suicide risk, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 7 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new non-invasive treatment called Personalized Ultrasonic Brain Stimulation, which uses ultrasonic waves to target specific brain areas in people with depression. The goal is to determine if this approach can improve symptoms in those who haven't found relief from traditional antidepressants or therapy. Participants should have experienced a moderate-to-severe depressive episode for at least two months and have tried at least two unsuccessful depression treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you avoid changes to your psychiatric treatments, including medications, for the duration of the study.

What prior data suggests that this ultrasonic brain stimulation is safe for individuals with depression?

Research has shown that ultrasonic brain stimulation is usually well-tolerated. One study found it to be a precise and safe method for stimulating the brain without surgery. This technique uses sound waves to target specific brain areas. Another study supports its safety, indicating that low-intensity ultrasound can be a safe option for brain treatments. However, the complete safety profile is still under investigation, as some details remain unclear. Overall, early findings suggest this treatment is likely safe, but further research is needed to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for depression?

Unlike the standard treatments for depression, which often include medications like SSRIs or therapies such as cognitive behavioral therapy, ultrasonic brain stimulation offers a fresh approach. This technique uses low-intensity focused ultrasound to target specific brain areas, like the subgenual cingulate cortex and the anterior limb of the internal capsule, which are key players in depression. By directly stimulating these brain regions, it may provide faster and potentially more effective relief from depressive symptoms. Researchers are particularly excited because this non-invasive method could offer a new lifeline for patients who don't respond well to traditional treatments.

What evidence suggests that this ultrasonic brain stimulation is effective for depression?

Research shows that low-intensity transcranial focused ultrasound stimulation (LTFUS) can help with depression. In this trial, participants will receive LTFUS targeting specific brain areas. Group 1 will first receive LTFUS to the subgenual cingulate cortex (SCC), followed by the anterior limb of the internal capsule (ALIC). Group 2 will receive LTFUS to the ALIC first, then the SCC. Previous studies have shown that this treatment improved scores on a test measuring depression severity by focusing on specific brain areas linked to depression. Another study found early evidence that this method is safe and effective, offering a promising non-invasive way to change brain activity. This could be especially useful for people who do not respond to standard treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Brian J Mickey

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

This trial is for individuals with major depression who haven't found relief with standard treatments. Participants must be eligible based on MRI scans and willing to undergo non-invasive brain stimulation. People are excluded if they have metal implants, pacemakers, or conditions that affect the brain's structure.

Inclusion Criteria

Agrees to allow any and all forms of communication between the investigators/study staff and any healthcare provider who currently provides and/or has provided service to the patient/subject within at least two years of study enrollment for the purposes of eligibility confirmation or in case of a safety event

For participants of reproductive potential: negative pregnancy test or use of highly effective contraception for at least 1 month prior to baseline; agreement to use such a method throughout the study

Currently under the care of a licensed psychiatrist or other mental health care provider, or a licensed addiction medicine specialist and agrees to promptly inform the investigator or the study staff of any change in these providers

Exclusion Criteria

Suicidal behavior (past year)

Serious suicide attempt 33 (lifetime)

Obsessive compulsive disorder, primary diagnosis (MINI, past month)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-intensity transcranial focused ultrasound stimulation targeting SCC and ALIC

7 weeks

Multiple visits on Days 0, 14, 15, 21, 22, 28, 29, 35, 49

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Personalized Ultrasonic Brain Stimulation

Trial Overview The study tests personalized low-intensity focused ultrasound stimulation (LTFUS) on two different brain areas: the subcallosal cingulate cortex (SCC) and the anterior limb of internal capsule (ALIC). It uses MRIs to find the best target in each person's brain and checks changes using functional MRI.

How Is the Trial Designed?

Group I: Group 2: ALIC-SCC Experimental Treatment 2 Interventions

Low-intensity transcranial focused ultrasound stimulation (LTFUS) is delivered to the anterior limb of the internal capsule (ALIC) at the first stimulation visit, then LTFUS is delivered to the subgenual cingulate cortex (SCC) at the second stimulation visit.

Group II: Group 1: SCC-ALIC Experimental Treatment 2 Interventions

Low-intensity transcranial focused ultrasound stimulation (LTFUS) is delivered to the subgenual cingulate cortex (SCC) at the first stimulation visit, then LTFUS is delivered to the anterior limb of the internal capsule (ALIC) at the second stimulation visit.

Who Is Running the Clinical Trial?

Brian Mickey

Lead Sponsor

Trials

1

Recruited

30+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

The new transcranial pulse stimulation (TPS) technique using ultrashort ultrasound pulses shows promising safety and efficacy in modulating brain activity, with preclinical studies indicating large safety margins and effective neuromodulation.

In a clinical pilot study involving 35 Alzheimer's patients, TPS treatment led to significant improvements in neuropsychological scores, with effects lasting up to three months and correlating with enhanced memory network activity as shown by fMRI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy. Beisteiner, R., Matt, E., Fan, C., et al.[2023]

Transcranial ultrasound stimulation (TUS) can non-invasively target both cortical and deep brain structures with high spatial resolution, potentially allowing for precise neuromodulation that was previously only possible with invasive methods.

The mechanism of TUS involves ultrasound waves interacting with neuronal membranes, leading to changes in neuronal excitability, which could have significant implications for both basic research and clinical applications in neuromodulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive transcranial ultrasound stimulation for neuromodulation. Darmani, G., Bergmann, TO., Butts Pauly, K., et al.[2022]

A wearable low-intensity pulsed ultrasound (LIPUS) device was developed and tested, showing it can safely deliver ultrasound to the brain without causing significant thermal injury.

The study suggests that LIPUS has potential as a safe transcranial treatment for neurological diseases, which could help alleviate symptoms of mental illnesses like depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment of a Wearable Low-Intensity Pulsed Ultrasound Device for Relieving Mental Illness Symptoms. Qi, S., Chen, J.[2020]

In a study involving 12 healthy participants, transcranial pulse stimulation (TPS) was shown to significantly enhance the efficiency of the cortical sensorimotor network and improve axonal status in the stimulated area, indicating positive neuroplastic changes.

The effects of TPS were observed to last up to one week after stimulation, suggesting its potential for long-term benefits in treating neurological and psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain. Matt, E., Kaindl, L., Tenk, S., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06902298

Personalized Ultrasonic Brain Stimulation for Depression ... This study will evaluate a new form of non-invasive brain stimulation for individuals with depression. Personalized low-intensity transcranial focused ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05301036

Personalized Ultrasonic Brain Stimulation for Depression This study will evaluate a new form of non-invasive brain stimulation for individuals with depression. Personalized low-intensity transcranial focused ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39111747/

A Randomized, Double-Blind, Sham-Controlled Clinical Trial Our results reveal that tFUS stimulation clinically improved MADRS scores with network-level modulation of a sgACC subregion.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000993

Deep transcranial ultrasound stimulation using ... This study provides first-in-human evidence of the potential of mTUS as a precise, safe and effective non-invasive neuromodulation technique.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11838982/

Ultrasound applications in the treatment of major depressive ... Approximately 30% of patients with MDD do not respond to conventional antidepressant and psychotherapeutic treatments. Current treatment options ...

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. 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.