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

Trial Summary

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 data supports the effectiveness of this treatment for PTSD?

Research shows that transcutaneous vagus nerve stimulation (tVNS) can reduce stress-related symptoms in PTSD by blocking inflammatory responses and altering brain activity during stress, suggesting it may help manage PTSD symptoms. ^{1 2 3 4 5}

Is the combination of DGB and tVNS safe for humans?

Transcutaneous vagus nerve stimulation (tVNS) is considered safe and has been used for various conditions like epilepsy, depression, and anxiety. It is a non-invasive method that doesn't require surgery, making it a low-risk option for patients. ^{1 6 7 8 9}

How is the DGB + tVNS treatment for PTSD different from other treatments?

The DGB + tVNS treatment for PTSD is unique because it combines device-guided breathing with noninvasive transcutaneous vagus nerve stimulation, which can reduce stress-related inflammation and sympathetic nervous system responses without the need for medication or surgery. ^{1 2 3 4 5}

What is the purpose of this trial?

Post-traumatic stress disorder (PTSD) is a highly prevalent anxiety disorder that is associated with an increased risk of cardiovascular (CV) disease and hypertension. One potential mechanism is overactivation of the sympathetic nervous system (SNS), both at rest and particularly during stress. This study will evaluate whether 8 weeks of daily DGB therapy or transcutaneous vagus nerve stimulation (tVNS) therapy improves SNS activity at rest and during stress.

Research Team

Jeanie Park, MD

Principal Investigator

Emory University and the Atlanta VA Medical Center

Eligibility Criteria

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.

You use illegal drugs.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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 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 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 (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]

References

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

Transcutaneous Vagus Nerve Stimulation in Patients With Severe Traumatic Brain Injury: A Feasibility Trial. [2022]

2. Netherlands 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. [2023]

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

Quantifying acute physiological biomarkers of transcutaneous cervical vagal nerve stimulation in the context of psychological stress. [2023]

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

Noninvasive Cervical Vagal Nerve Stimulation Alters Brain Activity During Traumatic Stress in Individuals With Posttraumatic Stress Disorder. [2023]

5. United States 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. [2023]

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

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

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

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. [2022]

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

Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder. [2022]

9. United States 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. [2019]