tcVNS for PTSD

(VNS in PTSD Trial)

Overseen By Doug J Bremner, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Opiates, Benzodiazepines

Disqualifiers: TBI, Schizophrenia, Bipolar, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently on opiate or benzodiazepine treatment.

What data supports the effectiveness of this treatment for PTSD?

Research shows that transcutaneous cervical vagal nerve stimulation (tcVNS) can reduce stress responses and inflammation in people with PTSD, and may improve memory and emotional regulation. These findings suggest that tcVNS could be a promising treatment for managing PTSD symptoms. ^{1 2 3 4 5}

Is transcutaneous cervical vagal nerve stimulation (tcVNS) safe for humans?

Research on transcutaneous vagal nerve stimulation (tcVNS) suggests it is generally safe, with mild and temporary side effects like ear pain, headache, and tingling. A systematic review found no significant difference in the risk of adverse events between active tcVNS and control groups, and no severe adverse events were linked to tcVNS. ^{1 2 3 6 7}

How is tcVNS treatment different from other PTSD treatments?

tcVNS is unique because it is a non-invasive treatment that targets the vagus nerve through the skin on the neck, aiming to reduce stress responses and inflammation in PTSD patients. Unlike traditional medications or therapies, it directly influences the autonomic nervous system and brain activity related to stress and emotional regulation. ^{1 2 3 5 8}

What is the purpose of this trial?

This study effects the effects of transcutaneous cervical vagal nerve stimulation (tcVNS) or a sham control on brain, physiology, and PTSD symptoms in Veterans with posttraumatic stress disorder (PTSD). Veterans undergo brain imaging and physiological measures in conjunction with traumatic scripts before and after three months of twice daily treatment with tcVNS or sham stimulation at home.

Research Team

Doug J Bremner, MD

Principal Investigator

Atlanta VA Medical and Rehab Center, Decatur, GA

Eligibility Criteria

This trial is for Veterans aged 18-75 with PTSD. It's not suitable for those with recent substance abuse, positive pregnancy, serious medical conditions, significant brain injury or history of certain mental illnesses like schizophrenia or bipolar I disorder.

Inclusion Criteria

I am a veteran aged 18-75 diagnosed with PTSD.

Exclusion Criteria

Active opiate or benzodiazepine treatment

Positive pregnancy test

History of structural abnormality on brain MRI or CT if one has been performed in the past

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo brain imaging and physiological measures in conjunction with traumatic scripts

1 week

1 visit (in-person)

Treatment

Participants receive twice daily home treatment with tcVNS or sham stimulation

12 weeks

Follow-up

Participants are monitored for changes in brain activation, PTSD symptoms, and physiological measures

4 weeks

Treatment Details

Interventions

• sham
• tcVNS

Trial Overview The study tests the impact of transcutaneous cervical vagal nerve stimulation (tcVNS) versus a sham (fake treatment) on brain function and PTSD symptoms in Veterans. Participants will use the tcVNS or sham at home twice daily for three months.

Participant Groups

Group I: tcVNS Experimental Treatment 1 Intervention

Stimulation twice daily with transcutaneous Vagal Nerve Stimulation (tcVNS)

Group II: sham Active Control 1 Intervention

stimulation with sham

tcVNS is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Vagal Nerve Stimulation for:

• Treatment-resistant depression

Approved in European Union as Transcutaneous Vagal Nerve Stimulation for:

• Treatment-resistant depression
• Epilepsy

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

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 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]

In a study involving 15 PTSD patients, active transcutaneous cervical Vagus Nerve Stimulation (tcVNS) significantly improved paragraph recall performance after two months, indicating potential benefits for memory function in PTSD (p < 0.05).

While active tcVNS showed trends of improved accuracy and recall in working memory tasks, these results were not statistically significant, suggesting that further research is needed to confirm the efficacy of tcVNS in enhancing cognitive functions in PTSD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of transcutaneous cervical vagus nerve stimulation on declarative and working memory in patients with Posttraumatic Stress Disorder (PTSD): A pilot study. Choudhary, T., Elliott, M., Euliano, NR., et al.[2023]

In a pilot study involving 22 combat veterans, transcutaneous vagal nerve stimulation (tVNS) was found to be well tolerated and improved vagal tone, indicating a positive effect on the autonomic nervous system related to PTSD symptoms.

tVNS also moderated the autonomic response to stress, suggesting it may help regulate emotional dysregulation in veterans with PTSD, particularly those with a history of mild traumatic brain injury (mTBI).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive Vagal Nerve Stimulation Effects on Hyperarousal and Autonomic State in Patients with Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury: Preliminary Evidence. Lamb, DG., Porges, EC., Lewis, GF., et al.[2020]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Transcutaneous cervical vagus nerve stimulation (tcVNS) effectively blocks inflammatory responses, specifically IL-6 and IFNγ, triggered by traumatic stress reminders in patients with PTSD, as shown in a study involving 30 subjects.

The study indicates that tcVNS can mitigate both behavioral and physiological stress responses in PTSD patients, suggesting its potential as a therapeutic intervention for managing PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial. Bremner, JD., Gurel, NZ., Jiao, Y., et al.[2022]

Transcutaneous cervical vagus nerve stimulation (tcVNS) significantly reduces ghrelin levels in individuals exposed to stress, indicating its potential as a treatment for stress-related psychiatric disorders, based on a study involving 55 participants.

The study found that after exposure to personalized traumatic stress and mental challenges, participants receiving active tcVNS had lower ghrelin levels compared to those receiving sham stimulation, suggesting that tcVNS effectively modulates hormonal responses to stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagal nerve stimulation modulates stress-induced plasma ghrelin levels: A double-blind, randomized, sham-controlled trial. Moazzami, K., Pearce, BD., Gurel, NZ., et al.[2023]

References

1. 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]

2. 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]

3. 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]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of transcutaneous cervical vagus nerve stimulation on declarative and working memory in patients with Posttraumatic Stress Disorder (PTSD): A pilot study. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Non-invasive Vagal Nerve Stimulation Effects on Hyperarousal and Autonomic State in Patients with Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury: Preliminary Evidence. [2020]

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

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

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

Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial. [2022]

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

Transcutaneous vagal nerve stimulation modulates stress-induced plasma ghrelin levels: A double-blind, randomized, sham-controlled trial. [2023]