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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called transcutaneous cervical vagal nerve stimulation (tcVNS) to determine its effectiveness in reducing PTSD symptoms in veterans. Participants will use either the real tcVNS device or a sham device at home twice daily for three months. The study examines changes in brain activity and physiological responses before and after treatment. Veterans diagnosed with PTSD, who have not experienced a traumatic brain injury or substance abuse problem in the past year, might be suitable candidates for this trial. As an unphased trial, it offers veterans the chance to contribute to groundbreaking research that could lead to new PTSD treatments.

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 prior data suggests that transcutaneous cervical vagal nerve stimulation (tcVNS) is safe for treating PTSD?

Research shows that using a device on the neck to stimulate a nerve, known as tcVNS, is generally safe for people with PTSD. Studies have found that tcVNS can reduce stress without causing harmful side effects. For instance, it can lower levels of certain stress-related chemicals in the body, such as interleukin-6, which is linked to inflammation. One study found that tcVNS helps reduce the physical stress reactions triggered by traumatic memories.

While the research is promising, most evidence comes from smaller studies. Participants have generally tolerated the treatment well, with no serious side effects reported. This suggests that tcVNS is a safe option for people with PTSD, but more research is needed to confirm its long-term safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for PTSD?

Transcutaneous Vagal Nerve Stimulation (tcVNS) is unique because it offers a non-invasive approach to treating PTSD by targeting the vagus nerve through the skin. Unlike standard PTSD treatments, which often involve medications like SSRIs or therapy sessions that require time to produce results, tcVNS leverages electrical stimulation to potentially provide a quicker and more direct effect on the nervous system. Researchers are excited about tcVNS because it could offer a safe, convenient, and potentially faster alternative to traditional treatments, opening up new pathways for managing PTSD symptoms.

What evidence suggests that tcVNS might be an effective treatment for PTSD?

This trial will compare two treatments for PTSD: transcutaneous Vagal Nerve Stimulation (tcVNS) and a sham treatment. Research has shown that using a device on the neck to stimulate a nerve, as in tcVNS, can help reduce stress in people with PTSD. Studies have found that it lowers automatic stress reactions, such as increased heart rate and sweating, when traumatic memories arise. It might also improve focus and memory in people with PTSD. Overall, this treatment appears to calm the body's stress systems, potentially easing PTSD symptoms. ^{1 6 7 8 9}

Who Is on the Research Team?

Doug J Bremner, MD

Principal Investigator

Atlanta VA Medical and Rehab Center, Decatur, GA

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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 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 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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7739181/

Transcutaneous cervical vagal nerve stimulation reduces ... The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on autonomic responses to acute stress in patients with PTSD.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05517304

Transcutaneous Vagal Nerve Stimulation in Veterans With ... This study effects the effects of transcutaneous cervical vagal nerve stimulation (tcVNS) or a sham control on brain, physiology, and PTSD symptoms in Veterans ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032723008625

Effect of transcutaneous cervical vagus nerve stimulation ... We analyzed the effect of transcutaneous cervical VNS (tcVNS) on attention, declarative and working memory in PTSD patients.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33344717/

A double-blind, randomized, sham controlled trial - PubMed Transcutaneous cervical vagal nerve stimulation reduces sympathetic responses to stress in posttraumatic stress disorder: A double-blind, ...

5. medrxiv.org medrxiv.org/content/10.1101/2020.02.10.20021626v3

Transcutaneous Cervical Vagal Nerve Stimulation ... tcVNS attenuates sympathetic arousal associated with stress related to traumatic memories as well as mental stress in patients with PTSD.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2352289520300540

Transcutaneous cervical vagal nerve stimulation reduces ... tcVNS attenuates sympathetic arousal associated with stress related to traumatic memories as well as mental stress in patients with PTSD.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8474180/

Transcutaneous vagal nerve stimulation blocks stress-induced ... Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000609

Vagus nerve stimulation therapy for treatment-resistant PTSD VNS therapy was safe and feasible to deliver. •. After therapy, all participants no longer met the criteria for PTSD diagnosis. •.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8580056/

A Pilot Study of Effects on PTSD Symptoms and Interleukin-6 ... We previously showed that transcutaneous Vagus Nerve Stimulation (tcVNS) blocks inflammatory (interleukin (IL)-6) responses to stress in PTSD. The purpose of ...