Low Intensity Focused Ultrasound for Depression and Anxiety

(LIFU Trial)

Overseen By Emily Aiken, MA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ocean State Research Institute, Inc.

Disqualifiers: Seizure disorder, Brain surgery, Alcohol use, others

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

Compensation: Varies

Number of Visits: 14

Duration: 6 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new brain stimulation method called low intensity focused ultrasound (LIFU) on veterans with depression and anxiety. LIFU uses sound waves to reach deep brain areas that current treatments can't. The study aims to see if LIFU is safe and effective in changing brain activity to help with these conditions.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients should be on stable treatments for more than 6 weeks, which suggests you may continue your current medications if they are stable.

How is Low Intensity Focused Ultrasound (LIFU) different from other treatments for depression and anxiety?

Low Intensity Focused Ultrasound (LIFU) is unique because it is a non-invasive brain stimulation technique that uses sound waves to target specific brain areas, unlike traditional treatments like medication or talk therapy. This method is similar to Low-Field Magnetic Stimulation (LFMS), which also offers rapid mood-enhancing effects, but LIFU uses ultrasound instead of magnetic fields. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Low Intensity Focused Ultrasound for Depression and Anxiety?

Research suggests that Low Intensity Focused Ultrasound (LIFU) can safely and precisely modulate brain activity, offering a non-invasive way to potentially improve outcomes in psychiatric conditions like depression. It has shown promise in modulating brain regions involved in psychiatric illnesses, and studies in animals have indicated it may reduce depression-like behaviors. ^{6 7 8 9 10}

Who Is on the Research Team?

Noah S Philip, MD

Principal Investigator

VA Providence Healthcare System

Are You a Good Fit for This Trial?

This trial is for veterans with depression and/or anxiety who have been stable on treatments for over 6 weeks. Healthy volunteers without psychiatric disorders or medications in the past 6 months can also join. Exclusions include those with brain surgery, severe head injuries, substance abuse issues, pacemakers, metal in the head, severe vision/hearing/hand impairments, pregnancy, inability to follow protocols or very severe symptoms.

Inclusion Criteria

I haven't had major depression, PTSD, or any psychiatric treatment for over 6 months.

I have been diagnosed with major depression, with or without anxiety.

I have noticeable symptoms and have been on stable treatment for over 6 weeks.

Exclusion Criteria

I have a history of seizures or serious brain-related illnesses.

Greater than moderate alcohol or substance use disorders (last six months; excluding nicotine/caffeine)

I have had brain surgery or have a pacemaker/implanted CNS device.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive LIFU application during two visits, with neuroimaging and neuropsychological testing

6 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including safety assessments and neurological exams

6 months

Up to 6 visits (in-person)

Extension

Optional extended follow-up for additional safety monitoring and assessments

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Low Intensity Focused Ultrasound

Trial Overview The study tests Low Intensity Focused Ultrasound (LIFU) as a non-invasive way to target deep brain structures linked to depression and anxiety. It will assess safety and ability of LIFU to alter brain activity during tasks. Participants undergo up to 14 visits including neuroimaging and neuropsychological testing; some receive LIFU while performing tasks.

How Is the Trial Designed?

Group I: Target Site Low Intensity Focused Ultrasound Experimental Treatment 1 Intervention

Low Intensity focused ultrasound of the target region. These are at a fundamental frequency = 650kHz, PRF = 10Hz, pulse width = 5ms, duty cycle = 5%; ISPTA.3 of 720 mW/cm2. As in prior studies, each sonication includes 10 pulsations, each lasting 30s, followed by 30s pause intervals; two 10-minute administrations provided per LIFU session.

Group II: Control Site Low Intensity Focused Ultrasound Active Control 1 Intervention

Low Intensity focused ultrasound of the control region. These are at a fundamental frequency = 650kHz, PRF = 10Hz, pulse width = 5ms, duty cycle = 5%; ISPTA.3 of 720 mW/cm2. As in prior studies, each sonication includes 10 pulsations, each lasting 30s, followed by 30s pause intervals; two 10-minute administrations provided per LIFU session.

Who Is Running the Clinical Trial?

Ocean State Research Institute, Inc.

Lead Sponsor

Trials

3

Recruited

280+

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 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 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 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]

High-density gel polymer matrices are effective couplants for low-intensity focused ultrasound (LIFU) neuromodulation, showing low acoustic attenuation (3.3%) and minimal beam distortion, making them suitable for clinical use.

The study highlights the importance of using standardized methods for preparing these gels to ensure consistent performance, as factors like thickness and de-gassing can significantly affect acoustic transmission and pressure attenuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. Strohman, A., In, A., Stebbins, K., et al.[2023]

In a study involving 30 participants with treatment-resistant major depressive disorder, three 20-minute sessions of low field magnetic stimulation (LFMS) were found to significantly reduce depressive symptoms compared to sham treatment, indicating its potential as a rapid-acting therapy.

The mood-enhancing effects of LFMS were not observed after the first or second session, suggesting that multiple treatments are necessary to achieve significant improvements in mood, highlighting the need for further research on optimal treatment schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind pilot dosing study of low field magnetic stimulation (LFMS) for treatment-resistant depression (TRD). Dubin, MJ., Ilieva, IP., Deng, ZD., et al.[2023]

In a study involving 84 subjects with treatment-resistant depression, Low-Field Magnetic Stimulation (LFMS) did not show a significant improvement in mood compared to sham treatment after two and four days of therapy.

While LFMS was generally well tolerated, the results suggest that more intensive or longer-duration treatments may be necessary to observe therapeutic effects, as no substantial differences were found in primary and secondary outcome measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, proof-of-concept (POC) trial of Low-Field Magnetic Stimulation (LFMS) augmentation of antidepressant therapy in treatment-resistant depression (TRD). Fava, M., Freeman, MP., Flynn, M., et al.[2022]

In a study of 183 adolescents and young adults, significant differences in neural activity were found between patients with major depressive disorder (MDD) and bipolar disorder (BD), particularly in the cortico-limbic-striatal neural system.

MDD patients exhibited abnormal neural activity predominantly in the left hemisphere, while BD patients showed bilateral abnormalities, suggesting distinct neural patterns that could help differentiate between the two disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alteration of cortico-limbic-striatal neural system in major depressive disorder and bipolar disorder. Jiang, X., Dai, X., Kale Edmiston, E., et al.[2018]

In a study involving 13 patients with major depressive disorder (MDD) and 14 healthy controls, resting-state fMRI revealed that MDD patients had significantly higher brain activity in the right medial prefrontal area compared to controls.

Conversely, MDD patients showed significantly lower brain activity in the left parietal region, suggesting that these alterations in brain activity may help explain the underlying mechanisms of depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Research on amplitude of low-frequency fluctuation in patients with major depression based on resting-state functional magnetic resonance imaging]. Qiu, H., Liu, H., He, Q., et al.[2018]

In a study involving 36 participants (18 with major depressive disorder and 18 healthy controls), patients with MDD exhibited increased amplitude of low-frequency oscillations (ALFF) in specific brain regions like the right fusiform gyrus and cerebellum, indicating altered brain activity associated with depression.

The findings suggest that these changes in LFO amplitude across various brain regions may be linked to emotional and cognitive disturbances in MDD, providing insights into the underlying network imbalances related to the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amplitude of low-frequency oscillations in first-episode, treatment-naive patients with major depressive disorder: a resting-state functional MRI study. Wang, L., Dai, W., Su, Y., et al.[2022]

Citations

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

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

2. 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]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

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

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

Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A double-blind pilot dosing study of low field magnetic stimulation (LFMS) for treatment-resistant depression (TRD). [2023]

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

Double-blind, proof-of-concept (POC) trial of Low-Field Magnetic Stimulation (LFMS) augmentation of antidepressant therapy in treatment-resistant depression (TRD). [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Alteration of cortico-limbic-striatal neural system in major depressive disorder and bipolar disorder. [2018]

9. China pubmed.ncbi.nlm.nih.gov

[Research on amplitude of low-frequency fluctuation in patients with major depression based on resting-state functional magnetic resonance imaging]. [2018]

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

Amplitude of low-frequency oscillations in first-episode, treatment-naive patients with major depressive disorder: a resting-state functional MRI study. [2022]