Ultrasound Therapy for PTSD

Overseen By Elisabeth Wilde, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Utah

Disqualifiers: Inability to complete MRI, Suicidal ideation

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

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Diadem, Low-Intensity Transcranial Focused Ultrasound Stimulation, Ultrasonic Neuromodulation for PTSD?

Research suggests that non-invasive brain stimulation, like the one used in Diadem, may help improve treatments for PTSD by enhancing brain activity. Additionally, focal brain stimulation has shown potential as a treatment for PTSD, indicating that similar methods could be effective. ^{1 2 3 4 5}

How is the treatment Diadem different from other PTSD treatments?

Diadem, or Low-Intensity Transcranial Focused Ultrasound Stimulation, is unique because it uses sound waves to target specific areas of the brain non-invasively, unlike traditional treatments that often involve medication or more invasive procedures. This approach is part of a new wave of neuromodulation therapies that aim to alter brain activity without surgery. ^{1 2 4 6 7}

What is the purpose of this trial?

This study will evaluate a new form of non-invasive deep brain therapy for individuals with post-traumatic stress disorder (PTSD). Low-intensity transcranial focused ultrasound stimulation will first be delivered using a range of stimulation parameters during psychophysical and physiological monitoring. A well-tolerated stimulation protocol will be selected for subsequent testing in a blinded randomized sham-controlled cross-over trial. The trial will evaluate brain target engagement using magnetic resonance imaging and numerical scales of PTSD, cognitive performance, and mood.

Research Team

Jan Kubanek, PhD

Principal Investigator

University of Utah

Elisabeth Wilde, PhD

Principal Investigator

University of Utah

Eligibility Criteria

This trial is for individuals with a confirmed diagnosis of PTSD, indicated by a score greater than 20 on the PCL-5 assessment. It's not suitable for those who don't meet this specific diagnostic threshold.

Inclusion Criteria

You have been diagnosed with PTSD and your PCL-5 score is higher than 20.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Stimulation and Monitoring

Low-intensity transcranial focused ultrasound stimulation delivered with various parameters during psychophysical and physiological monitoring

4 weeks

Multiple visits for stimulation and monitoring

Blinded Randomized Sham-Controlled Cross-Over Trial

Testing of a well-tolerated stimulation protocol in a blinded randomized sham-controlled cross-over trial

8 weeks

Regular visits for treatment and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Diadem

Trial Overview The study is testing 'Diadem', which uses low-intensity focused ultrasound to stimulate the brain non-invasively in people with PTSD. The effectiveness will be measured through MRI scans and assessments of PTSD severity, cognitive function, and mood changes.

Participant Groups

Group I: Active stimulation Experimental Treatment 1 Intervention

Low-intensity transcranial focused ultrasound stimulation of deep brain targets affected by PTSD.

Group II: Sham stimulation Placebo Group 1 Intervention

Sham stimulation that applies the device in the same way as verum but only delivers auditory sounds correspoding to the ultrasonic pulses.

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Findings from Research

The study involved 12 Veterans with PTSD who underwent six sessions of virtual reality exposure combined with transcranial direct current stimulation (tDCS), targeting the ventromedial prefrontal cortex, showing that this combination can be applied without technical issues.

Results indicated that the tDCS combined with VR significantly reduced physiological arousal and led to a clinically meaningful decrease in PTSD symptoms, suggesting potential for this approach in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined transcranial direct current stimulation with virtual reality exposure for posttraumatic stress disorder: Feasibility and pilot results. van 't Wout-Frank, M., Shea, MT., Larson, VC., et al.[2021]

Focal brain stimulation shows promise as a treatment for PTSD, with evidence suggesting that targeting specific brain areas involved in fear response and emotion regulation can enhance treatment efficacy.

Current research indicates that downregulating fear-related circuits (like the amygdala) and upregulating emotion regulation areas (like the prefrontal cortex) may be key to improving PTSD treatment outcomes, but more studies are needed to validate these targets and explore additional ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining focal brain stimulation targets for PTSD using neuroimaging. van Rooij, SJH., Sippel, LM., McDonald, WM., et al.[2022]

Recent studies indicate that drugs with serotonergic actions can provide significant symptom relief for PTSD patients over an 8-week treatment period, enhancing their ability to engage in therapy.

Controlled and double-blind trials have shown positive outcomes, suggesting that pharmacotherapy can be an effective component of a comprehensive treatment plan for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-traumatic stress disorder. Vargas, MA., Davidson, J.[2007]

Posttraumatic stress disorder (PTSD) symptoms arise from dysregulation of the fear system, which can be studied in animals through Pavlovian fear conditioning to understand the neurobiology behind these responses.

The review highlights both established and emerging treatments for PTSD, including pharmacotherapies and device-based interventions, developed through a translational model that bridges laboratory research to clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials. Bowers, ME., Ressler, KJ.[2021]

Posttraumatic stress disorder (PTSD) affects 1-9% of the general population, but its prevalence can rise to 19-70% among those who have experienced traumatic events, indicating a significant impact on affected individuals.

Selective serotonin reuptake inhibitors (SSRIs) have been shown to be effective in treating PTSD, with studies demonstrating significant improvements in both civilian and veteran populations, and no gender-related differences in clinical response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Posttraumatic stress disorder (PTSD)]. Martényi, F.[2022]

In a study involving 30 rats, 40 Hz acousto-optical stimulation significantly reduced anxiety-like symptoms associated with PTSD, as evidenced by improved behavior in tests like the elevated plus maze and open field test after 7 days of stimulation.

The mechanism behind this improvement appears to be linked to increased levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB, suggesting that the stimulation enhances synaptic plasticity in the brain regions involved in anxiety regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of 40 Hz multisensory stimulation on trauma-induced anxiety-like behavior in rats]. Yin, JY., Gao, XJ., Zhang, XY., et al.[2023]

Electroconvulsive therapy has shown success in treating some individuals with PTSD who have not responded to other treatments, although reports on its effectiveness are limited.

New neuromodulation strategies, such as repetitive transcranial magnetic stimulation and vagus nerve stimulation, are being explored as experimental treatments for PTSD, indicating a growing interest in alternative therapeutic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulatory treatments for post-traumatic stress disorder (PTSD). Koek, RJ., Roach, J., Athanasiou, N., et al.[2019]

References

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

Combined transcranial direct current stimulation with virtual reality exposure for posttraumatic stress disorder: Feasibility and pilot results. [2021]

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

Defining focal brain stimulation targets for PTSD using neuroimaging. [2022]

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

Post-traumatic stress disorder. [2007]

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

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials. [2021]

5. Hungary pubmed.ncbi.nlm.nih.gov

[Posttraumatic stress disorder (PTSD)]. [2022]

6. China pubmed.ncbi.nlm.nih.gov

[Effects of 40 Hz multisensory stimulation on trauma-induced anxiety-like behavior in rats]. [2023]

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

Neuromodulatory treatments for post-traumatic stress disorder (PTSD). [2019]