Low-Intensity Focused Ultrasound for Depression

Overseen By Charlie Palmer, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must be taking: SSRIs, augmentation

Must not be taking: Non-prescribed psychoactives

Disqualifiers: Schizophrenia, Bipolar, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 week

Trial Summary

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

The trial does not specify if you need to stop taking your current medications, but it does allow medications for treating major depressive disorder. You cannot start a new antidepressant treatment when joining the study.

How does Low-Intensity Focused Ultrasound treatment for depression differ from other treatments?

Low-Intensity Focused Ultrasound (LIFU) is unique because it is a non-invasive treatment that uses sound waves to precisely target and modulate specific brain areas involved in depression, unlike traditional treatments like medication or electroconvulsive therapy. It offers reversible effects and high spatial precision without the need for surgery, setting it apart from other brain stimulation techniques. ^{1 2 3 4 5}

What is the purpose of this trial?

The Investigators are proposing to demonstrate safety and efficacy of LIFUP for treatment resistant major depressive disorder in a ten-patient pilot study. LIFUP is an emerging treatment with the advantage of being able to target subcortical transcranial targets, which may have superior efficacy or a shorter treatment course compared to other available treatments such as transcranial magnetic stimulation. This study will investigate the effect of this stimulation on the left subgenual cingulate cortex, a highly connected node in the depression network that is correlated with clinical symptomatology.

Eligibility Criteria

This trial is for adults aged 18-70 with major depressive disorder (MDD) that's moderate to severe and hasn't improved after trying at least two SSRI treatments and one additional therapy. People with anxiety can join if MDD is their main issue, but not those with schizophrenia or bipolar disorder. Participants need stable health, normal vision and hearing (with aids if needed), and a history of depression lasting over a year.

Inclusion Criteria

I have been diagnosed with severe depression.

My vision and hearing are normal, or corrected to be normal.

I have tried and not responded to two SSRIs and one additional treatment.

Exclusion Criteria

I am not using any non-prescribed drugs except for my depression treatment.

Contraindication to enter the MRI environment

Urine Pregnancy Test: If the subject is a woman of childbearing potential and /or a man capable of fathering a child before, during, and/or after participation precaution should be taken. Examples of acceptable methods of birth control for participants involved in the study includes: birth control pills, patch, IUD, condom, sponge, diaphragm with spermicide, or avoiding sexual activity that could cause the subject to become pregnant

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive either LIFUP or sham stimulation with crossover of sham participants into the treatment group halfway through the treatment course. Treatments are delivered over two days within one week.

1 week

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with assessments at one week and one month post-treatment.

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Low-Intensity Focused Ultrasound

Trial Overview The study tests Low-Intensity Focused Ultrasound Pulsation (LIFUP) on the left subgenual cingulate cortex in the brain to see if it helps people who haven't gotten better from standard depression treatments. It compares real LIFUP treatment against sham (fake) treatment in ten patients to check its safety and effectiveness.

Participant Groups

Group I: Sham/Active Group Experimental Treatment 2 Interventions

This group will receive sham LIFUP for four treatments over one day, followed by four total treatments of active LIFUP across one day one week after sham.

Group II: Active/Active Group Experimental Treatment 1 Intervention

This group will receive eight total treatments of LIFUP across two days one week apart (four treatments each day).

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Findings from Research

The dual-crossed transducer system achieved high spatial resolution in targeting small brain regions in mice, with a focal volume of under 0.52 μm³ and a focal diameter of 1 mm, making it effective for precise neuromodulation.

In vivo experiments demonstrated successful brain stimulation in wild-type mice, evidenced by observable movements, confirming the system's capability for noninvasive and specific targeting of brain circuits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound stimulation with high spatial resolution. Kim, S., Jo, Y., Kook, G., et al.[2021]

Low intensity focused ultrasound (LIFU) is a promising non-invasive technology that can precisely modulate brain activity, offering a new approach to studying and potentially treating psychiatric illnesses.

LIFU has been shown to safely affect both cortical and subcortical brain regions, distinguishing it from other neuromodulatory techniques due to its spatial precision and reversible effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation-A Paradigm Shift in Psychiatric Research. Arulpragasam, AR., van 't Wout-Frank, M., Barredo, J., et al.[2022]

Low-intensity focused ultrasound (LIFU) is a promising noninvasive technique for neuromodulation that could improve treatment outcomes for patients with Major Depressive Disorder (MDD) and Obsessive-Compulsive Disorder (OCD) who do not respond to traditional therapies.

Current psychosurgical techniques, such as deep-brain stimulation, have variable success rates, with only about half of patients showing adequate response, highlighting the need for innovative approaches like LIFU to enhance personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized Definition of Surgical Targets in Major Depression and Obsessive-Compulsive Disorder: A Potential Role for Low-Intensity Focused Ultrasound? Guinjoan, SM.[2023]

A new low-intensity focused ultrasound (LIFU) stimulator with a focal depth controller has been developed to enhance the recovery of injured peripheral nerves and muscles, demonstrating effective targeting for neuromuscular rehabilitation.

In experiments, the stimulator achieved a high quality ultrasound stimulation intensity of 496 mW/cm2, successfully targeting a rat's sciatic nerve, indicating its potential for improving rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity focused ultrasound stimulator using focal depth controller for improved targeting in neuromuscular rehabilitation. Sungjin Oh, ., Dong Hwee Kim, ., Inchan Youn, .[2020]

Low-intensity pulsed ultrasound (LIPUS) treatment over four weeks significantly improved depression-like behaviors in rats, indicating its potential as a nonpharmaceutical treatment for depression.

LIPUS appears to work by enhancing key signaling pathways (BDNF/ERK/mTORC1) in the brain without causing any tissue damage, suggesting it is a safe and effective neuromodulation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity pulsed ultrasound ameliorates depression-like behaviors in a rat model of chronic unpredictable stress. Zhang, J., Zhou, H., Yang, J., et al.[2021]

References

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

Transcranial focused ultrasound stimulation with high spatial resolution. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation-A Paradigm Shift in Psychiatric Research. [2022]

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

Personalized Definition of Surgical Targets in Major Depression and Obsessive-Compulsive Disorder: A Potential Role for Low-Intensity Focused Ultrasound? [2023]

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

Low-intensity focused ultrasound stimulator using focal depth controller for improved targeting in neuromuscular rehabilitation. [2020]

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

Low-intensity pulsed ultrasound ameliorates depression-like behaviors in a rat model of chronic unpredictable stress. [2021]