Non-Invasive Vagus Nerve Stimulation for PTSD

Overseen By Imanuel R Lerman, MD MSc

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: VA Office of Research and Development

Must not be taking: Anti-inflammatories, Chronic pain meds

Disqualifiers: Psychosis, Bipolar, Major depression, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 1 week

88 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants continue taking standard medications used to treat PTSD. However, if you take anti-inflammatory medications for chronic conditions or medications for chronic pain, you will be excluded from the trial.

What data supports the effectiveness of the treatment Cervical Transcutaneous Vagus Nerve Stimulation for PTSD?

Research shows that Cervical Transcutaneous Vagus Nerve Stimulation (tcVNS) can reduce stress responses and inflammation in people with PTSD, and it may also improve memory and brain activity related to traumatic stress. ^{1 2 3 4 5}

Is non-invasive vagus nerve stimulation safe for humans?

Non-invasive vagus nerve stimulation, including both cervical and auricular methods, is generally considered safe for humans. Studies show that adverse effects are mild and temporary, such as ear pain, headache, and tingling, with no severe adverse events linked to the treatment. ^{2 3 5 6 7}

How does cervical transcutaneous vagus nerve stimulation (tcVNS) differ from other treatments for PTSD?

Cervical transcutaneous vagus nerve stimulation (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 without the need for surgery or medication. This approach is different from traditional treatments like medications and psychotherapy, as it directly influences neurobiological systems involved in PTSD symptoms. ^{1 2 3 4 5}

What is the purpose of this trial?

The proposal aims to determine if non-invasive vagus nerve stimulation(nVNS) will alter: 1) the peripheral inflammatory biomarker profile, 2) the neural correlates of change in pain stimuli and 3) PTSD symptom severity and 4) life quality and function in Veterans with PTSD. The planned inflammatory biomarker and neuroimaging results can 1) promote knowledge of inflammatory and neurobiological mechanisms that contribute to pain in PTSD, and 2) advance the ability to provide targeted neuromodulation based interventions that support improved life quality and function for Veterans. These goals are consistent with the VA's mission to sponsor research examining variables related to pathogenesis, diagnosis, and(ultimately) treatment of neuropsychiatric disorders.

Research Team

Imanuel R Lerman, MD MSc

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Eligibility Criteria

This trial is for male veterans aged 21-65 who have PTSD from deployment, with specific symptom severity scores. They must speak English and be able to follow the study schedule. Excluded are those with certain mental illnesses, recent evidence-based PTSD treatment, chronic pain management, risky alcohol/drug use, or conditions worsened by the treatment.

Inclusion Criteria

You have experienced a traumatic event, but your symptoms do not meet the severity criteria for a diagnosis of PTSD.

For PTSD: Previously deployed, experienced a traumatic event, and meets Clinician-Administered PTSD Scale for DSM-5(CAPS-5) symptom cluster severity criteria for PTSD diagnosis, as well as CAPS total cut-off score > 33

I am a man aged between 21 and 65.

Exclusion Criteria

You have taken part in another drug study or have been given experimental drugs within the last month.

I've had a head injury with unconsciousness over a minute and symptoms afterwards.

I have not had major heart, artery, or neck issues, nor seizures or fainting in the past year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham transcutaneous vagus nerve stimulation daily for 7 days

1 week

7 visits (in-person)

Follow-up

Participants are monitored for changes in PTSD symptoms, functional life quality, and inflammatory biomarkers

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Cervical Transcutaneous Vagus Nerve Stimulation

Trial Overview The study tests if non-invasive vagus nerve stimulation (nVNS) can change inflammation markers, brain response to pain stimuli in PTSD patients, and improve their symptoms and life quality. Participants will receive either active nVNS or a sham (fake) version as a comparison.

Participant Groups

Group I: Transcutaneous Vagus Nerve Stimulation Active Control 1 Intervention

Cervical Transcutaneous vagus nerve stimulation. Participants will undergo once daily cervical transcutaneous vagus nerve stimulation.

Group II: Sham Vagus Nerve Stimulation Placebo Group 1 Intervention

Sham Cervical Transcutaneous Vagus Nerve Stimulation. Participants will undergo once daily sham cervical transcutaneous vagus nerve stimulation.

Cervical Transcutaneous Vagus Nerve Stimulation is already approved in United States for the following indications:

Approved in United States as VNS Therapy System 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 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 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 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]

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 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]

Transcutaneous vagus nerve stimulation (tVNS) shows promise for treating various conditions in pediatric patients, but current studies lack specific protocols and justification for its use in this age group, as none of the 15 identified studies focused exclusively on children.

There are no dedicated tVNS devices for pediatric use, and existing studies do not adequately address neurodevelopmental considerations, highlighting the need for more research on age-appropriate stimulation parameters and protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. Sigrist, C., Torki, B., Bolz, LO., et al.[2023]

References

1. 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]

2. 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]

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

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

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. 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. 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 Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. [2023]