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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Low-Intensity Focused Ultrasound (LIFUP) to determine its safety and effectiveness for individuals with major depressive disorder who haven't found relief with other treatments. LIFUP uses sound waves to target specific brain areas, potentially alleviating depression symptoms faster than current options. Participants will receive either the real treatment or a sham (inactive) version to compare results. The trial seeks individuals who have had major depressive disorder for more than a year and have not improved with at least two types of antidepressants.

As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for depression.

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.

What prior data suggests that Low-Intensity Focused Ultrasound is safe for treating depression?

Research has shown that Low-Intensity Focused Ultrasound (LIFUP) is generally safe and well-tolerated. One study found that varying amounts of LIFUP did not cause significant side effects, and MRI scans confirmed no changes in brain structure after treatment. Other studies have tested LIFUP's safety for treating major depressive disorder, with results indicating it is well-tolerated. Although this treatment remains under study, the absence of major negative effects in these studies suggests it is likely safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for depression, such as antidepressants and psychotherapy, work by altering brain chemistry or providing cognitive support over time. However, Low-Intensity Focused Ultrasound (LIFUP) offers a non-invasive method that directly targets specific areas of the brain with sound waves. Researchers are excited about LIFUP because it has the potential to quickly modulate brain activity without the side effects often associated with medications. Additionally, LIFUP could offer a more immediate improvement in symptoms compared to traditional treatments that may take weeks to show significant effects.

What evidence suggests that Low-Intensity Focused Ultrasound is effective for depression?

Research has shown that Low-Intensity Focused Ultrasound (LIFUP) holds promise for treating major depressive disorder. Studies have found that LIFUP can reach deep brain areas linked to depression, potentially offering advantages over treatments like transcranial magnetic stimulation. Early results suggest it may help reduce symptoms of depression and anxiety. In this trial, participants will be divided into two groups: the Sham/Active Group, receiving sham LIFUP followed by active LIFUP, and the Active/Active Group, receiving only active LIFUP. This method targets the left subgenual cingulate cortex, a brain area connected to depression symptoms. While more research is needed, these initial findings offer hope for individuals with depression that hasn't responded to other treatments. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1094715924006627

A Comprehensive Review of Low-Intensity Focused ... Low-intensity focused ultrasound (LIFU) is gaining increased interest as a potential therapeutic modality for a range of neuropsychiatric diseases.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11321877/

Effect of Low-Intensity Transcranial Focused Ultrasound ... These results suggest that tFUS may effectively reduce both depression and anxiety in patients with MDD. Our results further demonstrate that ...

3. fusfoundation.org fusfoundation.org/posts/clinical-trial-investigates-low-intensity-focused-ultrasound-for-depression/

Clinical Trial Investigates Low-Intensity ... Preliminary data show that LIFU may be able to reach deep structures of the brain involved with depression and anxiety that traditional ...

4. reporter.nih.gov reporter.nih.gov/project-details/10209047

Low intensity focused ultrasound - NIH RePORTER PROJECT SUMMARY/ABSTRACT Current treatments for depression and anxiety are often limited by partial efficacy and significant side effects.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05147142

NCT05147142 | Low Intensity Focused Ultrasound: a New ... In this study, the investigators will test if this technique can be used to change brain activity in areas that are connected to depression and anxiety symptoms ...

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

A Randomized, Double-Blind, Sham-Controlled Clinical Trial The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05147142

NCT05147142 | Low Intensity Focused Ultrasound: a New ... The primary objectives of this study are to test the safety and tolerability of LIFU, evaluate the feasibility of using LIFU to reduce brain activity, and ...

8. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1211566/full

Low-intensity focused ultrasound targeting the nucleus ... Results: Both LIFU doses were safe and well-tolerated based on reported adverse events and MRI scans revealed no structural changes (0 min, 24 h ...