Vagus Nerve Stimulation for TBI

(taVNS Trial)

Overseen By Ricardo Jorge, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Disqualifiers: Neurological, Cardiovascular, Pulmonary, 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: 3

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial aims to evaluate whether transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive brain stimulation method, can improve attention and memory in veterans with traumatic brain injury (TBI) and depression and/or posttraumatic stress disorder (PTSD). The study seeks to answer two main questions: 1. Can active taVNS improve attention and memory compared to sham (placebo) stimulation? 2. Does taVNS affect heart rate variability (HRV)? taVNS delivers a gentle electrical current to the vagus nerve through electrodes placed on the ear, targeting brain areas involved in attention and memory without requiring surgery. This study uses a crossover design, meaning all participants will experience two sessions: one with active taVNS and one with sham stimulation. The sham session feels similar but does not deliver actual stimulation, allowing researchers to compare the two and understand taVNS's effects on the brain. In a single visit, participants will: * Complete eligibility screening (questionnaires and vital signs). * Undergo two sessions (one active and one sham), randomly assigned. * Perform attention tasks before and after each session. * Have their heart rate monitored during the sessions. The findings will help determine whether taVNS could be an effective treatment for improving attention and memory in veterans with TBI.

Do I have to stop taking my current medications for the trial?

If you are taking psychotropic medication, you need to have been stable on it for 3 months. If you are taking stimulants, you must stop taking them 12 hours before the sessions.

What data supports the effectiveness of the treatment Vagus Nerve Stimulation for TBI?

Research shows that transcutaneous vagus nerve stimulation (tVNS) is a non-invasive method that has been effective in reducing seizure frequency in patients with drug-resistant epilepsy and is being explored for other conditions like depression. Although specific data for TBI is limited, the positive effects in other neurological conditions suggest potential benefits for TBI patients. ^{1 2 3 4 5}

Is vagus nerve stimulation safe for humans?

Non-invasive vagus nerve stimulation (VNS), including transcutaneous methods like tVNS and taVNS, is generally considered safe for humans. Studies show that it has a good safety profile with only mild and temporary side effects such as ear pain, headache, and tingling, and it avoids the risks associated with surgical implantation. ^{1 2 6 7 8}

How does transcutaneous vagus nerve stimulation (tVNS) differ from other treatments for traumatic brain injury (TBI)?

Transcutaneous vagus nerve stimulation (tVNS) is unique because it is a non-invasive treatment that stimulates the vagus nerve through the skin, particularly at the outer ear, without the need for surgery. This makes it safer and more accessible compared to traditional, surgically implanted vagus nerve stimulation, and it is being explored for its potential to improve recovery of consciousness and cognitive function in TBI patients. ^{1 2 3 5 6}

Eligibility Criteria

This trial is for veterans with traumatic brain injury (TBI) who may also have depression or PTSD. Participants will undergo non-invasive stimulation of the vagus nerve to see if it improves attention and memory. They must complete questionnaires, vital sign checks, and be able to attend a single visit for two sessions.

Inclusion Criteria

Veterans with a history of deployment to Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF), Operation New Dawn (OND) or other post 9/11 war on terrorism

Right-handedness

I am between 25 and 64 years old.

Exclusion Criteria

I have a history of brain, heart, or lung disease.

Current substance use disorder (exception: mild cannabis use disorder allowed)

Medical implants such as cardiac defibrillators, pacemakers, or deep brain stimulators

Timeline

Screening

Participants are screened for eligibility to participate in the trial

40 minutes

1 visit (in-person)

Session 1

Participants complete a computer-based attention task and receive either active or sham taVNS stimulation

40 minutes

1 visit (in-person)

Break

Participants have a short break between sessions

Session 2

Participants complete the same procedures as Session 1 with the alternate type of stimulation

40 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the sessions

Not specified

Treatment Details

Interventions

• Transcutaneous Vagus Nerve Stimulation

Trial Overview The study tests transcutaneous auricular vagus nerve stimulation (taVNS), comparing active electrical current delivery to sham (placebo) treatment in a crossover design—each participant experiences both treatments randomly on the same day while performing attention tasks.

Participant Groups

Group I: taVNS active stimulation Active Control 2 Interventions

Participants will receive transcutaneous auricular vagus nerve stimulation (taVNS) using electrodes placed on the left ear. A low-level electrical current will be delivered to stimulate the vagus nerve. This stimulation is designed to activate brain areas involved in attention and memory.

Group II: Sham (Placebo) taVNS Placebo Group 2 Interventions

Participants will undergo sham stimulation, where electrodes are placed on the left ear to mimic the experience of active taVNS. However, no electrical current will be delivered to the vagus nerve. This sham condition enables a direct comparison with active taVNS, ensuring that any observed changes in working memory and attention can be attributed to the taVNS intervention.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Michael E. DeBakey VA Medical Center

Collaborator

Trials

68

Recruited

17,200+

Findings from Research

Transcutaneous vagus nerve stimulation (tVNS) was found to be feasible and safe for patients with persistent impairment of consciousness after severe traumatic brain injury (TBI), with minimal side effects reported during an eight-week treatment period.

Out of five patients treated, three showed significant improvements in consciousness as measured by the Coma Recovery Scale-Revised (CRS-R), suggesting that tVNS may have potential benefits for recovery following severe TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagus Nerve Stimulation in Patients With Severe Traumatic Brain Injury: A Feasibility Trial. Hakon, J., Moghiseh, M., Poulsen, I., et al.[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) 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) 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]

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) 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]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

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]

References

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

Transcutaneous Vagus Nerve Stimulation in Patients With Severe Traumatic Brain Injury: A Feasibility Trial. [2022]

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

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

3. 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]

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

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas. [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. England pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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