Non-invasive Nerve Stimulation for PTSD

Recruiting at 3 trial locations

Overseen By John Williamson, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Disqualifiers: Severe psychiatric illness, Drug abuse, others

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

Compensation: Varies

Number of Visits: 1

Duration: 8 hours

221 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two types of nerve stimulation can alter sleep patterns in people with PTSD (Post-Traumatic Stress Disorder). The researchers aim to determine how these noninvasive treatments might improve sleep by testing different methods of nerve stimulation through the skin. Veterans with PTSD, with or without a history of mild traumatic brain injury (TBI), are ideal candidates for this trial. Participants will be divided into two groups, each receiving a different nerve stimulation method to compare effects. As an unphased trial, this study allows participants to contribute to innovative research that could lead to new treatment options for PTSD-related sleep issues.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you have a history of drug abuse, you may not be eligible to participate.

What prior data suggests that these nerve stimulation techniques are safe for PTSD patients?

Research has shown that transcutaneous nerve stimulation, which sends gentle electrical pulses through the skin, is safe and effective for treating PTSD (post-traumatic stress disorder).

For the first type of nerve stimulation, studies have found that it can block certain stress responses linked to inflammation, suggesting it might help with PTSD symptoms. This non-invasive method does not require surgery or inserting devices into the body, making it generally safer and easier for patients to handle.

The second type of nerve stimulation also shows promise. Research has demonstrated its safety and practicality, with patients reporting significant and lasting improvements. Like the first type, it is non-invasive.

Overall, both types of nerve stimulation appear well-tolerated, with no major safety concerns reported in studies. These methods present interesting options for managing PTSD symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcutaneous nerve stimulation for PTSD because it offers a non-invasive approach to treatment, unlike traditional options like medication and therapy. This technique involves stimulating nerves through the skin at specific locations, which may help regulate brain activity and reduce PTSD symptoms without the side effects associated with drugs. Additionally, it provides a potential alternative for individuals who have not found relief from conventional treatments.

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

Studies have shown that transcutaneous vagus nerve stimulation (tcVNS) can reduce stress in people with PTSD by blocking certain body responses. Research suggests that this nerve stimulation might also decrease PTSD-related anxiety by altering brain cell connections. Early results indicate that tcVNS can improve PTSD symptoms and is safe and easy to use. In this trial, participants will receive one of two types of noninvasive nerve stimulation. Both types have shown promise for long-lasting improvements in PTSD symptoms. Overall, researchers are exploring these treatments because they could offer new ways to manage PTSD. ^{1 2 3 6 7}

Who Is on the Research Team?

John Williamson, PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for veterans who have PTSD, with or without a history of mild traumatic brain injury (TBI). It's not open to those with severe psychiatric illnesses not related to PTSD/TBI, significant medical conditions affecting cognition, or current drug abuse issues.

Inclusion Criteria

I am a veteran with PTSD, with or without a mild brain injury.

Exclusion Criteria

History of severe psychiatric illness unrelated to PTSD or TBI

Other medical conditions of severity that may impair cognition

Current illicit or prescription drug abuse

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive non-invasive nerve stimulation to assess changes in sleep architecture

8 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcutaneous nerve stimulation location 1
• Transcutaneous nerve stimulation location 2

Trial Overview The study is testing two different locations of transcutaneous nerve stimulation to see how they affect sleep patterns in individuals suffering from PTSD and/or TBI.

How Is the Trial Designed?

Group I: Noninvasive nerve stimulation type I Experimental Treatment 1 Intervention

This group will receive one type of nerve stimulation

Group II: Noninvasive nerve stimulation type II Active Control 1 Intervention

This group will receive second type of nerve stimulation

Transcutaneous nerve stimulation location 1 is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as TENS for:

• Pain management
• Muscle rehabilitation

Approved in United States as TENS for:

• Chronic pain
• Acute pain
• Muscle spasms

Approved in United States as tVNS for:

• Epilepsy
• Depression
• Sleep disorders

Approved in Canada as TENS for:

• Pain relief
• Muscle rehabilitation

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

US Department of Veterans Affairs

Collaborator

Trials

881

Recruited

502,000+

North Florida/South Georgia Veterans Health System

Collaborator

Trials

8

Recruited

2,000+

Published Research Related to This Trial

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]

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]

A systematic review of 51 studies involving 1322 participants found that transcutaneous vagus nerve stimulation (tVNS) is generally safe and well tolerated, with only 2.6% of participants dropping out due to side effects.

The most common side effects included local skin irritation (18.2%), headache (3.6%), and nasopharyngitis (1.7%), with very few serious adverse events linked to tVNS, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Redgrave, J., Day, D., Leung, H., et al.[2019]

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) showed a significant 34% reduction in seizure frequency in patients with drug-resistant epilepsy over a 20-week trial involving 39 participants, compared to a 2.9% reduction in the control group.

The tVNS method was well-tolerated by participants, suggesting it is a safe alternative to surgical implantation for vagus nerve stimulation, warranting further research with longer observation periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons learned from transcutaneous vagus nerve stimulation (tVNS). Hamer, HM., Bauer, S.[2019]

Lower skin impedance was found at optimal electrode sites for TENS treatment, suggesting that these sites may enhance the effectiveness of pain management techniques.

In a study with 24 healthy volunteers, both optimal and sham TENS treatments significantly increased pressure pain thresholds compared to a placebo, indicating that TENS is effective for pain relief, regardless of skin impedance at the electrode sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin impedance is not a factor in transcutaneous electrical nerve stimulation effectiveness. Vance, CG., Rakel, BA., Dailey, DL., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) is a promising non-invasive alternative to traditional vagus nerve stimulation (VNS) for treating conditions like epilepsy and depression, which can be invasive and have side effects.

There is ongoing research into the best stimulation parameters and sites for tVNS, particularly focusing on stimulation at the outer ear, to optimize its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas. Hilz, MJ., Bolz, A.[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]

Transcutaneous vagus nerve stimulation (tVNS) significantly reduces seizure frequency in patients with drug-resistant epilepsy, based on a meta-analysis of three studies involving 280 patients.

tVNS appears to have a low incidence of adverse effects, with headaches being the most common, making it a safer alternative for patients who cannot undergo invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation for the treatment of drug-resistant epilepsy: a meta-analysis and systematic review. Wu, K., Wang, Z., Zhang, Y., et al.[2022]

Citations

1. 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 ...

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

Vagus nerve stimulation therapy for treatment-resistant PTSD We developed a fundamentally novel neuromodulation-based therapy for treatment-resistant PTSD. This approach is premised on coupling prolonged exposure therapy.

3. 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.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01627301

Sympathetic Overactivity in Post-traumatic Stress Disorder 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 ...

5. nature.com nature.com/articles/s41398-025-03535-9

Transcutaneous auricular vagus nerve stimulation ... In this study, we aimed to elucidate whether and how taVNS influences anxiety-like behaviors elicited by PTSD, focusing on synaptic plasticity ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12344430/

Transcutaneous vagal nerve stimulation for the treatment of ... Vagal nerve stimulation (VNS) has recently emerged as a prospective therapeutic approach for addressing trauma- and stressor-related disorders (TSRDs).

7. bmjopen.bmj.com bmjopen.bmj.com/content/15/1/e093467

Transauricular vagus nerve stimulation in preventing post ... Transauricular vagus nerve stimulation (ta-VNS) modulates the autonomic nervous system by stimulating the nucleus tractus solitarius while affecting PTSD- ...