Ultrasound for Depression

(LIFU CANVAS Trial)

Overseen By Danielle E Clark, MA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Laureate Institute for Brain Research, Inc.

Must be taking: Antidepressants

Must not be taking: Benzodiazepines, Anticonvulsants

Disqualifiers: Neurocognitive disorder, Diabetes, Hypertension, Pregnancy, Substance use, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with Major Depressive Disorder (MDD) who haven't found relief with typical treatments. It uses low-intensity focused ultrasound, a non-invasive procedure, to target specific brain pathways involved in depression. The researchers aim to understand how these brain areas contribute to depressive symptoms and to find better treatments. Individuals who have battled depression for a while and haven't responded to medications or therapy might be suitable candidates. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to innovative treatments for depression.

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

The trial requires that your current treatments, including medications, be stable for at least six weeks before participating. However, you cannot use benzodiazepines or anticonvulsants in the 7 days prior to screening.

What prior data suggests that low-intensity focused ultrasound is safe for treating depression?

Research has shown that low-intensity focused ultrasound (LIFU) is safe for people. Studies have found that LIFU is usually well-tolerated, with few reports of serious side effects. In trials using LIFU for depression and anxiety, participants experienced only minor issues. These results suggest that LIFU is a safe option for exploring new treatments for conditions like major depressive disorder. However, everyone's experience can differ, so discussing any personal concerns with a healthcare provider is essential. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the potential of low-intensity focused ultrasound (LIFU) for treating depression because it offers a non-invasive approach that targets specific brain pathways. Unlike traditional treatments like antidepressants, which can take weeks to work and often have side effects, LIFU uses sound waves to stimulate precise areas of the brain, potentially offering faster relief. The technique's precision in targeting areas like the thalamo-anterior cingulate cortex and the thalamo-orbitofrontal cortex could lead to more effective and personalized treatment options for depression. This innovative approach could revolutionize how we manage depression by providing a quicker, more targeted alternative to current therapies.

What evidence suggests that low-intensity focused ultrasound might be an effective treatment for treatment-resistant depression?

Research shows that low-intensity focused ultrasound (LIFU) could help treat major depressive disorder (MDD), especially for those who haven't found relief with other treatments. This trial will explore different applications of LIFU, including targeting the thalamo-anterior cingulate cortex tract and the thalamo-orbitofrontal cortex tract. Studies indicate that LIFU can improve depression by targeting specific brain areas, such as the anterior cingulate cortex and the orbitofrontal cortex. For instance, one study found that LIFU improved depression symptoms by affecting brain networks. Additionally, research suggests that LIFU might boost levels of brain-derived neurotrophic factor (BDNF), a protein important for brain health. Early findings suggest that LIFU could be a safe and effective option for managing treatment-resistant MDD. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with Major Depressive Disorder (MDD) who haven't responded to standard treatments. It aims to help those at high risk of disability and suicide by targeting specific brain circuits related to negative emotions.

Inclusion Criteria

Consent for random observations of pathology

DSM-5-TR diagnosis of MDD confirmed by MINI structured interview and consultation with a board-certified psychiatrist

Fluent English speaker capable of written consent

Exclusion Criteria

PROMIS (Cognitive Function scale) score ≤40 collected at baseline

Pregnancy or lactation

Positive test result(s) for alcohol or drugs of abuse

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-intensity focused ultrasound (LIFU) or sham stimulation targeting thalamo-OFC or thalamo-ACC white matter tracts

1 session

1 visit (in-person)

Post-Sonication Monitoring

Participants are monitored for changes in functional connectivity and behavioral models up to 30 minutes post-sonication

30 minutes

1 visit (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 focused ultrasound

Trial Overview The study tests low-intensity focused ultrasound as a noninvasive treatment for MDD. It will modulate brain connections in 120 participants, potentially offering new insights into managing severe depression symptoms.

How Is the Trial Designed?

Group I: Thalamo-Anterior Cingulate Cortex Tract LIFU Sonication Experimental Treatment 1 Intervention

An 80-second train of 20-millisecond bursts of ultrasound (0.5 MHz), repeated every 200 milliseconds (400 bursts). It is estimated a 75% tissue attenuation of energy when the ultrasound wave reaches its target, therefore the investigators will set the free-field Intensity Spatial-Peak Pulse-Average (ISPPA) at 9.04 Watt /cm2 or 518 kPascal (to achieve 2.26 Watt/cm2 estimated derated ISPPA). Any modeling of actual energy delivery will be made a posteriori employing BabelBrain® software embedded in the Brainsight® neuronavigation system.

Group II: Thalamo- Orbitofrontal Cortex Tract LIFU Sonication Experimental Treatment 1 Intervention

An 80-second train of 20-millisecond bursts of ultrasound (0.5 MHz), repeated every 200 milliseconds (400 bursts). It is estimated a 75% tissue attenuation of energy when the ultrasound wave reaches its target, therefore the investigators will set the free-field Intensity Spatial-Peak Pulse-Average (ISPPA) at 9.04 Watt /cm2 or 518 kPascal (to achieve 2.26 Watt/cm2 estimated derated ISPPA). Any modeling of actual energy delivery will be made a posteriori employing BabelBrain® software embedded in the Brainsight® neuronavigation system.

Group III: Sham LIFU Placebo Group 1 Intervention

An 80-second train of 20-millisecond bursts of ultrasound (0.5 MHz), repeated every 200 milliseconds (400 bursts). It is estimated a 75% tissue attenuation of energy when the ultrasound wave reaches its target, therefore the investigators will set the free-field Intensity Spatial-Peak Pulse-Average (ISPPA) at 9.04 Watt /cm2 or 518 kPascal (to achieve 2.26 Watt/cm2 estimated derated ISPPA). Any modeling of actual energy delivery will be made a posteriori employing BabelBrain® software embedded in the Brainsight® neuronavigation system.

Who Is Running the Clinical Trial?

Laureate Institute for Brain Research, Inc.

Lead Sponsor

Trials

53

Recruited

5,400+

Citations

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

Effect of Low-Intensity Transcranial Focused Ultrasound ... Our results reveal that tFUS stimulation clinically improved MADRS scores with network-level modulation of a sgACC subregion. This randomized, ...

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

A Comprehensive Review of Low-Intensity Focused ... In this study, we provide a review of the most recent LIFU literature covering three key domains: 1) the history of focused ultrasound technology, comparing it ...

3. medrxiv.org medrxiv.org/content/10.1101/2025.01.23.25320960v2.full-text

A systematic review of techniques and efficacy in clinical ... This systematic review critically analyzed published studies reporting the use of ultrasound to treat major depressive disorder and depressive- ...

4. mdpi.com mdpi.com/2076-3425/15/10/1129

Using Low-Intensity Focused Ultrasound to Treat ... The research field of using LIFU to stimulate specific targets of the brain associated to emotional processes, with the anticipation of effects on neurocircuits ...

5. pdfs.semanticscholar.org pdfs.semanticscholar.org/8df9/5248a8aacdbb4dc56d61f99cb26390a2ecca.pdf

Effect of Low-Intensity Transcranial Focused Ultrasound ... The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder. Methods ...

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

Clinical Trial Investigates Low-Intensity Focused ... A clinical trial is underway investigating the safety and feasibility of using low-intensity focused ultrasound (LIFU) to address anxiety and depression.

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. 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 ...