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

Trial Summary

What is the purpose of this trial?

In this study, our objective is to determine the effect of two different nerve stimulation types in changing sleep architecture.

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 data supports the effectiveness of this treatment for PTSD?

Transcutaneous vagus nerve stimulation (tVNS) has shown positive effects in treating drug-resistant epilepsy and depression, suggesting it may help with PTSD by modulating brain activity and improving mood. It is a non-invasive, safe, and low-cost alternative to traditional vagus nerve stimulation, which requires surgery. ^{1 2 3 4 5}

Is transcutaneous vagus nerve stimulation (tVNS) safe for humans?

Transcutaneous vagus nerve stimulation (tVNS) is generally considered safe and well-tolerated in humans, including pediatric patients, as it is non-invasive and does not require surgery. It has been used in studies for various conditions like epilepsy and depression, showing good safety profiles. ^{1 3 6 7 8}

How is transcutaneous nerve stimulation different from other PTSD treatments?

Transcutaneous nerve stimulation (TENS or tVNS) is unique because it is a non-invasive treatment that uses electrical impulses to stimulate nerves through the skin, potentially increasing norepinephrine activity in the brain, which is different from traditional PTSD treatments like medication or talk therapy. ^{1 3 5 8 9}

Research Team

John Williamson, PhD

Principal Investigator

University of Florida

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Noninvasive nerve stimulation type I Experimental Treatment 2 Interventions

This group will receive one type of nerve stimulation

Group II: Noninvasive nerve stimulation type II Active Control 2 Interventions

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+

Findings from Research

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) 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 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 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) 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]

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 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]

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]

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]

References

1. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas. [2022]

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

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

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

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

5. Australia pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation for the treatment of drug-resistant epilepsy: a meta-analysis and systematic review. [2022]

6. 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]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Lessons learned from transcutaneous vagus nerve stimulation (tVNS). [2019]

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

Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Skin impedance is not a factor in transcutaneous electrical nerve stimulation effectiveness. [2022]