DGB + tVNS for Post-Traumatic Stress Disorder

(SO-PTSD Trial)

Overseen By Jeanie Park, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Emory University

Must not be taking: Clonidine, MAO inhibitors

Disqualifiers: Heart disease, Illicit drug use, others

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

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to help veterans with PTSD manage symptoms, potentially lowering their risk of heart disease and high blood pressure. Researchers are testing two treatments: Device-Guided Breathing (DGB), which helps control breathing, and Transcutaneous Vagal Nerve Stimulation (tVNS), a method that gently stimulates a nerve in the neck. Participants will receive one of these treatments, or a similar non-active version, over eight weeks to determine if it calms the body's stress responses. Veterans with normal or slightly high blood pressure and PTSD may be eligible to participate. As an unphased trial, this study offers veterans a unique opportunity to contribute to innovative research that could enhance PTSD treatment options.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications known to affect the sympathetic nervous system, like clonidine, and monoamine oxidase inhibitors if you've used them in the last 14 days.

What prior data suggests that these devices are safe for treating PTSD?

Research has shown that device-guided breathing (DGB) is generally easy to use. In several studies, patients using DGB experienced less stress without major side effects, suggesting that DGB can help manage stress by calming the body. So far, no major safety concerns have been reported for this treatment.

Transcutaneous vagal nerve stimulation (tVNS) also appears safe. Research indicates that tVNS can help reduce symptoms of PTSD (post-traumatic stress disorder) and anxiety by sending a gentle electrical pulse to the vagus nerve, which plays a key role in controlling stress. Studies have found that tVNS is safe and practical, with no major harmful effects reported.

Overall, both DGB and tVNS have shown positive safety results in past studies. These treatments are being explored for their potential to improve symptoms related to PTSD and anxiety by calming the nervous system. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Device-Guided Breathing (DGB) and Transcutaneous Vagal Nerve Stimulation (tVNS) for treating Post-Traumatic Stress Disorder (PTSD) because these methods offer unique, non-drug approaches. Unlike traditional treatments like therapy or medication, DGB helps regulate breathing to naturally reduce anxiety and stress. tVNS, on the other hand, uses mild electrical stimulation to activate the vagal nerve, potentially calming the nervous system in a novel way. These approaches could provide new options for those who may not respond well to existing treatments or are seeking alternatives without medication side effects.

What evidence suggests that this trial's treatments could be effective for PTSD?

This trial will compare Device-Guided Breathing (DGB) and Transcutaneous Vagal Nerve Stimulation (tVNS) for managing PTSD symptoms. Research shows that DGB can help manage PTSD symptoms by reducing stress reactions in the body. Studies have found that using a DGB device for several weeks can calm the body's stress response, which is often too active in people with PTSD. This calming effect can lead to better control of anxiety and stress.

For tVNS, early findings suggest it may help improve mood and reduce anxiety by stimulating the vagus nerve, which helps regulate stress. Research has shown promising results in using tVNS to manage PTSD symptoms, with some studies noting improvements in anxiety and mood. Both treatments in this trial seem to offer potential benefits for people dealing with PTSD by targeting how the body handles stress. ^{1 2 6 7 8}

Who Is on the Research Team?

Jeanie Park, MD

Principal Investigator

Emory University and the Atlanta VA Medical Center

Are You a Good Fit for This Trial?

This trial is for prehypertensive and normotensive veterans with or without PTSD, aiming to study the effects of certain therapies on their nervous system. Pregnant individuals, those with serious systemic diseases, heart or vascular disease, autonomic dysfunction, excessive alcohol use, illicit drug users, and people on specific SNS-affecting medications or recent MAO inhibitors cannot participate.

Inclusion Criteria

I am a veteran with PTSD and my blood pressure is normal or slightly high.

I am a veteran with normal or slightly high blood pressure and do not have PTSD.

Exclusion Criteria

I have a history of heart or blood vessel disease.

I haven't taken MAO inhibitors in the last 14 days.

I have a history of a serious illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily DGB or tVNS therapy for 8 weeks to improve sympathetic activity and vascular function

8 weeks

Weekly check-ins (virtual or in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Device-Guided Breathing (DGB)
• Sham DGB
• Sham tVNS
• Transcutaneous Vagal Nerve Stimulation (tVNS)

Trial Overview The study tests if 8 weeks of daily Device-Guided Breathing (DGB) therapy or Transcutaneous Vagal Nerve Stimulation (tVNS) can improve sympathetic nervous system activity in veterans with PTSD. It includes control interventions like Sham tVNS and Sham DGB to compare results against.

How Is the Trial Designed?

Group I: Transcutaneous Vagal Nerve Stimulation (tVNS) Experimental Treatment 1 Intervention

Participants randomized to use a tVNS device to deliver mild electrical stimulation to the vagal nerve.

Group II: Device-guided Breathing (DGB) Experimental Treatment 1 Intervention

Participants randomized to the DGB group use a device to guide their breathing to a slow breathing rate.

Group III: Sham DGB Placebo Group 1 Intervention

Participants randomized to the sham DGB group use a device identical to the DGB device but respiratory rates are not guided lower than the physiological rate.

Group IV: Sham tVNS Placebo Group 1 Intervention

Participants randomized to use the sham tVNS device which vibrates but does not stimulate the vagal nerve.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

US Department of Veterans Affairs

Collaborator

Trials

881

Recruited

502,000+

Published Research Related to This Trial

Transcutaneous cervical vagal nerve stimulation (tcVNS) was shown to enhance brain activation in areas associated with trauma processing, such as the anterior cingulate and hippocampus, during exposure to traumatic stress reminders in a study of 22 participants.

Compared to sham stimulation, tcVNS resulted in significant changes in brain activity, suggesting it may help reverse neurobiological alterations linked to PTSD, potentially improving autonomic control and offering a new treatment avenue for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Cervical Vagal Nerve Stimulation Alters Brain Activity During Traumatic Stress in Individuals With Posttraumatic Stress Disorder. Wittbrodt, MT., Gurel, NZ., Nye, JA., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and effective neuromodulation therapy for a variety of conditions, including epilepsy, depression, and anxiety, indicating its broad therapeutic potential.

Despite its effectiveness, there is currently no standardization among taVNS devices, and further research is needed to clarify the relationship between stimulation parameters and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Wang, L., Wang, Y., Wang, Y., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) significantly reduced depression symptoms in patients with mild to moderate major depressive disorder (MDD), as evidenced by a notable decrease in Hamilton Depression Rating Scale scores after one month of treatment.

tVNS was found to modulate functional connectivity in the brain's default mode network, indicating potential mechanisms through which it may exert its antidepressant effects, particularly by altering connectivity with regions like the anterior insula and parahippocampus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder. Fang, J., Rong, P., Hong, Y., et al.[2022]

Transcutaneous Vagus Nerve Stimulation (tcVNS) significantly reduced PTSD symptoms by 31% compared to sham treatment over three months, indicating its potential efficacy as a therapeutic intervention.

tcVNS effectively blocked stress-induced increases in the inflammatory marker IL-6, suggesting that its mechanism of action may involve reducing inflammation associated with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Cervical Vagal Nerve Stimulation in Patients with Posttraumatic Stress Disorder (PTSD): A Pilot Study of Effects on PTSD Symptoms and Interleukin-6 Response to Stress. Bremner, JD., Wittbrodt, MT., Gurel, NZ., et al.[2023]

Transcutaneous cervical VNS (tcVNS) significantly reduces sympathetic responses to acute stress in patients with PTSD, as evidenced by decreased heart rate and improved vascular function during stress exposure.

The study involved 25 participants and demonstrated that tcVNS not only helps with stress related to traumatic memories but also has positive effects during mental stress, indicating its potential as a therapeutic intervention for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous cervical vagal nerve stimulation reduces sympathetic responses to stress in posttraumatic stress disorder: A double-blind, randomized, sham controlled trial. Gurel, NZ., Wittbrodt, MT., Jung, H., et al.[2023]

Transcutaneous cervical vagus nerve stimulation (tcVNS) significantly reduces sympathetic nervous system activity and enhances parasympathetic tone in response to stress, as evidenced by measurable changes in heart function and peripheral vascular responses in 24 participants with trauma exposure.

The study demonstrated that tcVNS effectively modulates autonomic responses not only immediately after stress but also after other stressors, suggesting its potential as a non-invasive tool for managing stress-related autonomic dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantifying acute physiological biomarkers of transcutaneous cervical vagal nerve stimulation in the context of psychological stress. Gurel, NZ., Huang, M., Wittbrodt, MT., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Transcutaneous vagus nerve stimulation (tVNS) was found to significantly increase salivary alpha amylase (SAA) levels and reduce the decline of salivary cortisol in healthy participants, indicating a modulation of hormonal indices related to noradrenergic function.

However, tVNS did not show any significant effects on psychophysiological measures such as P3 amplitude or pupil size, suggesting that while it may influence hormonal responses, it does not impact certain cognitive or physiological indices in the same way.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential. Warren, CM., Tona, KD., Ouwerkerk, L., et al.[2019]

Transcutaneous vagus nerve stimulation (tVNS) was found to be feasible and safe for patients with persistent impairment of consciousness after severe traumatic brain injury (TBI), with minimal side effects reported during an eight-week treatment period.

Out of five patients treated, three showed significant improvements in consciousness as measured by the Coma Recovery Scale-Revised (CRS-R), suggesting that tVNS may have potential benefits for recovery following severe TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagus Nerve Stimulation in Patients With Severe Traumatic Brain Injury: A Feasibility Trial. Hakon, J., Moghiseh, M., Poulsen, I., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7642907/

Eight weeks of device-guided slow breathing decreases ... These data suggest that long-term use of DGB may lead to a sustained dampening of sympathetic reactivity to mental stress in PTSD.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01627301

Sympathetic Overactivity in Post-traumatic Stress Disorder The purpose of this study is to determine if device-guided slow breathing or tVNS improves sympathetic activity and vascular function in persons with PTSD.

3. mddionline.com mddionline.com/business/could-device-guided-breathing-be-effective-for-ptsd-patients-

Could Device-guided Breathing Be Effective for PTSD ... Study results showed that RESPeRate, a portable electronic device that promotes slow, deep breathing, actually improved symptoms of patients suffering from PTSD ...

4. arch.astate.edu arch.astate.edu/cgi/viewcontent.cgi?article=1077&context=dnp-projects

Determining the Effectiveness of Deep Breathing Exercises in ... This section provides a background of the problem and, reviews relevant literature on the topic, explains the change frameworks and theoretical ...

5. frontiersin.org frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2022.678098/full

Reducing Test Anxiety by Device-Guided Breathing: A Pilot ... This paper addresses the effectiveness of using DGB as a self-treatment clinical tool for test anxiety reduction.

6. journals.physiology.org journals.physiology.org/doi/prev/20200826-aop/pdf/10.1152/ajpregu.00079.2020

Long-term Slow Breathing and Reactivity to Mental Stress Elevated resting blood pressure augments autonomic imbalance in posttraumatic stress disorder. 573. American journal of physiology Regulatory, integrative and ...

7. health.ny.gov health.ny.gov/health_care/medicaid/ebbrac/meetings/2024/docs/2024-11-07_freespira_rpt.pdf

Freespira for Panic Disorder and Posttraumatic Stress ... guided respiratory intervention, which leads the user through guided and monitored breathing ... safety outcomes from the 3 eligible studies.

8. link.springer.com link.springer.com/article/10.1007/s10055-025-01225-x

Evaluation of virtual reality-based guided imagery ... Moreover, only the VR group demonstrated significant improvements in post-traumatic growth, quality of life, and autonomic regulation indexed by ...