Vagus Nerve Stimulation for TBI

(taVNS Trial)

Overseen By Lane Witkowski Research Coordinator

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method called transcutaneous auricular vagus nerve stimulation (taVNS) to determine its effectiveness in helping veterans with traumatic brain injury (TBI), PTSD, or depression improve attention and memory. taVNS uses a gentle electrical current applied to the ear to stimulate the brain non-invasively, requiring no surgery. Participants will undergo two sessions: one with real stimulation and one with a sham setup for comparison. Veterans who have served in recent conflicts and have a history of TBI, PTSD, or depression might be suitable candidates. The outcomes will inform researchers if taVNS can effectively boost brain function in these conditions. As an unphased trial, this study offers veterans the chance to contribute to groundbreaking research that could lead to new treatments for improving brain function.

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 prior data suggests that this method is safe for veterans with TBI?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe for people. In earlier studies, taVNS proved to be a safe and practical method for patients with severe traumatic brain injury (TBI), with no obvious side effects reported, indicating patients tolerated the treatment well.

taVNS sends a gentle electrical current to the vagus nerve through small devices placed on the ear. This non-invasive method does not involve surgery. While past research has demonstrated the safety of taVNS, more controlled studies are needed to understand its long-term effects and benefits for various conditions. Overall, current findings suggest that taVNS is a safe option for improving brain functions like attention and memory in people with TBI. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcutaneous vagus nerve stimulation (taVNS) for traumatic brain injury (TBI) because it offers a non-invasive way to possibly improve attention and memory. Unlike standard treatments that often involve medication or rehabilitation therapies, taVNS uses a low-level electrical current delivered through electrodes on the ear to stimulate the vagus nerve, which can activate brain areas involved in cognitive functions. This method could provide a novel approach to enhancing brain recovery processes, potentially offering benefits without the side effects associated with some pharmacological treatments.

What evidence suggests that this method is effective for improving attention and memory in veterans with TBI?

This trial will compare active transcutaneous vagus nerve stimulation (taVNS) with a sham (placebo) version. Studies have shown that using a device on the skin to stimulate the vagus nerve, known as taVNS, can be a safe and practical option for people with traumatic brain injury (TBI). Research suggests that taVNS might help reduce seizures after a brain injury by lowering certain chemicals in the brain. It has also been used alongside therapy to improve movement skills after a stroke. Although more detailed studies are needed to confirm its effects on attention and memory, early results are promising for its use in brain-related conditions. Overall, taVNS shows potential for improving brain function without surgery. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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 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 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 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 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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10133680/

Randomized trial of transcutaneous auricular vagus nerve ... This study attempts to investigate the effectiveness of taVNS in DoC by means of Coma Recovery Scale-Revised (CRS-R), Magnetic resonance imaging (MRI), ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014488621002958

Potential roles of vagus nerve stimulation on traumatic ... From this study, it can be deduced that VNS potentially reduced the incidence of post-traumatic epilepsy by reducing extracellular glutamate levels and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32227429/

Transcutaneous Vagus Nerve Stimulation in Patients With ... Conclusion: We demonstrated that tVNS is a feasible and safe VNS strategy for patients following severe TBI. Controlled studies are needed to ...

4. neuromodulationjournal.org neuromodulationjournal.org/article/S1094-7159(21)00253-1/abstract

Transcutaneous Vagus Nerve Stimulation in Patients With ... The feasibility of tVNS was evaluated in five patients presenting with diffuse axonal injury and reduced dominant EEG activity one month following severe TBI.

5. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1390217/full

Neurorehabilitation with vagus nerve stimulation Our review suggests that VNS (non-invasive or invasive) paired with rehabilitation can improve motor outcomes after stroke in humans.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1094715921002531

Transcutaneous Vagus Nerve Stimulation in Patients With ... We demonstrated that tVNS is a feasible and safe VNS strategy for patients following severe TBI. Controlled studies are needed to clarify whether tVNS has a ...

7. journals.lww.com journals.lww.com/nrronline/fulltext/2022/08000/efficacy_and_safety_of_transcutaneous_auricular.37.aspx

Efficacy and safety of transcutaneous auricular vagus ... There were no obvious side effects. These findings suggest that ta-VNS combined with conventional rehabilitation training for the treatment of acute ischemic or ...