Focused Ultrasound for Post-Traumatic Stress Disorder

(PTSD FUS Trial)

Overseen By Alison Gorbatov

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

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

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

Duration: 4 weeks

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that veterans be on stable psychiatric treatments before starting the study, so you may not need to stop your current medications. However, the protocol does not specify any changes to existing medications.

What data supports the effectiveness of the treatment Focused Ultrasound for Post-Traumatic Stress Disorder?

Focused ultrasound is a promising noninvasive treatment that has shown potential in brain stimulation and reducing inflammation in other conditions. It combines the precision of deep brain stimulation with the noninvasiveness of other brain therapies, and has been used successfully in treating obsessive-compulsive disorder and controlling inflammation, which suggests it might be effective for PTSD as well. ^{1 2 3 4 5}

Is focused ultrasound generally safe for humans?

Focused ultrasound, when used correctly, is generally safe for humans, with mild and temporary side effects like tenderness and redness. Rare side effects can occur, often due to improper technique, but they are usually mild and resolve on their own. ^{6 7 8 9 10}

How does focused ultrasound treatment for PTSD differ from other treatments?

Focused ultrasound is unique because it is a non-invasive treatment that uses sound waves to target specific brain areas, potentially opening the blood-brain barrier to enhance drug delivery. This method is different from traditional PTSD treatments, which often involve medication or talk therapy, as it directly interacts with brain structures without surgery or radiation. ^{4 11 12 13 14}

What is the purpose of this trial?

The goal of this study is to develop a new, non-invasive brain stimulation modality called low intensity focused ultrasound (FUS) as a psychiatric rehabilitation treatment for posttraumatic stress disorder (PTSD). FUS delivers energy comparable to that involved in diagnostic ultrasound but in a millimeter-sized envelope. Unlike currently available methods, the maximal FUS energy is delivered at a distance from a transducer on the scalp. Therefore, its promise is that it can deliver focal and reversible modulation to deeper brain regions involved in PTSD. The investigator team has previously conducted first-in-human research in FUS, and this study builds upon that work to conduct a phase II, dose-finding study. This study will pursue two Aims; the first is whether FUS to the amygdala can improve symptoms, and the second will evaluate whether FUS improves function by reduced disability, over a 1-month period. Short and longer-term effects of FUS will be measured and all FUS parameters are within FDA-defined safety thresholds for diagnostic ultrasound.

Research Team

Noah S. Philip, MD

Principal Investigator

Providence VA Medical Center, Providence, RI

Eligibility Criteria

This trial is for veterans with PTSD. It's testing a new, non-invasive brain stimulation treatment using focused ultrasound (FUS). Participants should have PTSD symptoms that might be improved by targeting the amygdala in the brain. Details on specific inclusion and exclusion criteria are not provided.

Inclusion Criteria

I am a veteran with stable psychiatric treatment before starting the study.

I am a veteran aged 22-70 with chronic PTSD diagnosed by a professional.

Exclusion Criteria

Greater than mild traumatic brain injury, or any head injury within sixty days of ultrasound

Veterans with acute suicidality are also excluded

I have had brain surgery before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Targeting and Randomization

Participants receive an MRI scan for high-precision targeting and are randomized to receive sham or active FUS

1 week

1 visit (in-person)

Treatment

Participants receive sham or active FUS administrations up to three times per week

4 weeks

Up to 12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Periodic visits (in-person)

Treatment Details

Interventions

• Focused Ultrasound

Trial Overview The study is examining low intensity FUS as a potential psychiatric rehabilitation treatment for PTSD. The energy used is similar to diagnostic ultrasound but targets millimeter-sized areas deep within the brain, like the amygdala, to see if it can reduce symptoms and disability over one month.

Participant Groups

Group I: Verum low intensity focused ultrasound Active Control 1 Intervention

Verum (active) low intensity focused ultrasound, applied up to three times per week.

Group II: Sham low intensity focused ultrasound Placebo Group 1 Intervention

Sham (inactive) low intensity focused ultrasound, applied up to three times per week.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

Focused ultrasound is a noninvasive brain stimulation technique that offers precise targeting, combining benefits from both repetitive transcranial magnetic stimulation and deep brain stimulation.

High-intensity focused ultrasound is already being used in incisionless surgeries, such as capsulotomies for treating obsessive-compulsive disorder, showcasing its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound as a Neurotherapeutic: A Circuit- and System-Based Interrogation. Spivak, NM., Tyler, WJ., Bari, AA., et al.[2023]

Microfocused Ultrasound with Visualization (MFU-V) has a well-established safety profile, showing only mild and transient side effects like tenderness and redness, with rare adverse events typically linked to improper technique.

When used correctly, MFU-V treatments are safe, with most side effects resolving quickly and without lasting effects, indicating its efficacy in cosmetic dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the safety profile for microfocused ultrasound with visualization. Hitchcock, TM., Dobke, MK.[2022]

In a large retrospective analysis involving over 78,000 doses of ultrasound contrast agents (Definity and Optison), only 0.01% of patients experienced severe adverse reactions, indicating a strong safety profile for these agents.

The study found that severe reactions were primarily in outpatients, with no serious events reported in critically ill patients, suggesting that ultrasound contrast agents are safe for use in a variety of clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of deFinity and Optison for ultrasound image enhancement: a retrospective analysis of 78,383 administered contrast doses. Wei, K., Mulvagh, SL., Carson, L., et al.[2022]

In a phase 1 study involving 15 participants, intense ultrasound treatment for facial and neck tissues was found to be safe, with no significant adverse effects reported and only mild discomfort experienced by patients.

Histological analysis showed that the treatment created consistent thermal injury zones in the dermis without damaging the epidermis, indicating a targeted and effective approach for skin rejuvenation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pilot study of intense ultrasound therapy to deep dermal facial skin and subcutaneous tissues. Gliklich, RE., White, WM., Slayton, MH., et al.[2012]

References

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

Ultrasound as a Neurotherapeutic: A Circuit- and System-Based Interrogation. [2023]

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

Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans. [2023]

3. Ireland pubmed.ncbi.nlm.nih.gov

Differential evolution method to find optimal location of a single-element transducer for transcranial focused ultrasound therapy. [2022]

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

Skull Impact on the Ultrasound Beam Profile of Transcranial Focused Ultrasound Stimulation. [2020]

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

Focused ultrasound: concept for automated transcutaneous control of hemorrhage in austere settings. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Review of the safety profile for microfocused ultrasound with visualization. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety and U.S. Regulatory considerations in the nonclinical use of medical ultrasound devices. [2010]

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

Biological effects of ultrasound. [2019]

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

The safety of deFinity and Optison for ultrasound image enhancement: a retrospective analysis of 78,383 administered contrast doses. [2022]

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

Clinical pilot study of intense ultrasound therapy to deep dermal facial skin and subcutaneous tissues. [2012]

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

An all-ultrasound cranial imaging method to establish the relationship between cranial FUS incidence angle and transcranial attenuation in non-human primates in 3D. [2023]

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

A Spatial Multitarget Ultrasound Neuromodulation System Using High-Powered 2-D Array Transducer. [2022]

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

A High-Frequency Phased Array System for Transcranial Ultrasound Delivery in Small Animals. [2023]

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

A Comprehensive Study of Ultrasound Transducer Characteristics in Microscopic Ultrasound Neuromodulation. [2023]