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

Trial Summary

What is the purpose of this trial?

This study will evaluate a new form of non-invasive brain stimulation for individuals with depression. Personalized low-intensity transcranial focused ultrasound stimulation will be delivered using a range of stimulation parameters during psychological and physiological monitoring. Individualized optimal targets will be selected using structural MRI and diffusion tractography. Brain target engagement will be evaluated using functional MRI.

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 data supports the effectiveness of the treatment Personalized Ultrasonic Brain Stimulation for depression?

Research on ultrasound-based brain stimulation shows it can safely and effectively improve brain function in conditions like Alzheimer's disease, with benefits lasting up to three months. This suggests potential for treating other brain-related conditions, such as depression. ^{1 2 3 4 5}

Is ultrasonic brain stimulation safe for humans?

Research shows that low-intensity ultrasonic brain stimulation is generally safe for humans, with studies indicating no significant tissue damage or major side effects. It has been tested in both healthy individuals and patients with conditions like Alzheimer's, showing high treatment tolerability and no major side effects. ^{1 2 4 5 6}

How is Personalized Ultrasonic Brain Stimulation different from other treatments for depression?

Personalized Ultrasonic Brain Stimulation is unique because it uses focused ultrasound waves to target specific areas of the brain with high precision, reaching deep brain structures non-invasively. This method offers a novel way to modulate brain activity without the need for surgery, unlike traditional treatments that may involve medication or invasive procedures. ^{1 2 4 5 7}

Research Team

Brian J Mickey

Principal Investigator

University of Utah

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy. [2023]

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

First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain. [2022]

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

Transcranial ultrasonic stimulation modulates single-neuron discharge in macaques performing an antisaccade task. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Guidelines for successful motor cortex ultrasonic neurostimulation in mice. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Non-invasive transcranial ultrasound stimulation for neuromodulation. [2022]

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

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

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

Multi-Ring Ultrasonic Transducer on a Single Piezoelectric Disk For Powering Biomedical Implants. [2020]