Vagal Nerve Stimulation for Traumatic Brain Injury

Overseen By Shira Cohen-Zimerman, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Shirley Ryan AbilityLab

Disqualifiers: Depression, Substance abuse, Bioelectrical implants, others

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

Compensation: Varies

Number of Visits: 2

Duration: 2-7 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether stimulating a specific nerve in the ear can aid recovery of thinking skills after a mild to moderate traumatic brain injury (TBI). The treatment uses a device to send gentle electrical signals to the vagus nerve, potentially boosting brain recovery. Participants will receive either the active treatment, known as transcutaneous auricular vagus nerve stimulation, or a placebo version that mimics the treatment without the actual effect. Suitable candidates are those currently in rehabilitation for a recent TBI and able to use a keyboard independently. As an unphased trial, this study provides a unique opportunity to contribute to pioneering research that could enhance recovery options for TBI patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this technique is safe for enhancing cognitive recovery in TBI patients?

Research shows that transcutaneous auricular vagus nerve stimulation (tVNS) is generally safe. Studies have found that tVNS does not cause noticeable side effects and is well-tolerated. For example, one study reported no significant negative effects when tVNS was used alongside regular rehabilitation for another condition. Another review describes tVNS as a promising and safe option for treating consciousness disorders. Although more research is needed to understand its effects on traumatic brain injury (TBI) specifically, current evidence suggests that tVNS is a safe treatment choice for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about transcutaneous auricular vagus nerve stimulation for traumatic brain injury because it offers a non-invasive approach that directly targets the vagus nerve, potentially improving brain function and recovery. Unlike standard treatments like medication and rehabilitation therapies, this method uses electrical stimulation delivered through the skin, which could enhance neural pathways without the need for surgery or pharmaceuticals. By harnessing the body’s natural communication networks, this technique might offer a faster and safer alternative to support healing in brain injury patients.

What evidence suggests that transcutaneous auricular vagus nerve stimulation is effective for cognitive recovery in traumatic brain injury?

Research suggests that transcutaneous auricular vagus nerve stimulation (tVNS), a treatment that participants in this trial may receive, can aid in recovering thinking abilities in individuals with traumatic brain injuries (TBI). Studies have shown that tVNS boosts brain activity and improves behavior in patients who receive it. One study found that tVNS effectively and safely helped brain injury patients regain consciousness. In experiments with rats, this nerve stimulation also improved movement and thinking skills after a TBI. Overall, these findings indicate that tVNS could be a helpful tool for recovery from brain injuries. ^{1 5 6 7 8}

Who Is on the Research Team?

Shira Cohen-Zimerman, PhD

Principal Investigator

Shirley Ryan AbilityLab

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 who are in rehab due to a recent mild-moderate traumatic brain injury. Participants must be able to use a keyboard, understand and communicate in English, provide consent, and have good orientation awareness as measured by the O-Log.

Inclusion Criteria

I can use a keyboard, understand and speak English, consent on my own, and am aware of my surroundings.

I am 18-65 years old and currently in rehab for a recent brain injury.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either active tVNS or sham stimulation while performing cognitive tasks

2-7 days

2 sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcutaneous auricular vagus active nerve stimulation
• Transcutaneous auricular vagus sham nerve stimulation

Trial Overview The study tests if noninvasive ear clip devices delivering vagus nerve stimulation can help with cognitive recovery after brain injury. Some participants will receive real stimulation (active), while others get fake stimulation (sham) to compare results.

How Is the Trial Designed?

Group I: Transcutaneous auricular vagus nerve stimulation Active Control 1 Intervention

Active vagus nerve stimulation.

Group II: Sham Transcutaneous auricular vagus nerve stimulation Placebo Group 1 Intervention

Sham vagus nerve stimulation.

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

Published Research Related to This Trial

Transcutaneous auricular vagus nerve stimulation (taVNS) shows potential as a treatment for disorders of consciousness, particularly in patients with a minimally conscious state (MCS), as it significantly alters brain activity measured by EEG.

In patients with MCS, taVNS led to notable changes in both delta and beta brain wave energy across multiple regions, suggesting it may enhance brain connectivity and promote awakening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. Yifei, W., Yi, Y., Yu, W., et al.[2023]

In a study involving 17 healthy adults, transcutaneous auricular vagus nerve stimulation (taVNS) at the left tragus significantly increased brain activity in areas associated with the vagal pathway, indicating its potential efficacy in neuromodulation.

Compared to control stimulation at the earlobe, tragus stimulation resulted in greater activation in key brain regions, suggesting that taVNS could be a promising therapeutic approach for influencing brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review. Badran, BW., Dowdle, LT., Mithoefer, OJ., 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]

This study will evaluate the effectiveness and safety of transcutaneous auricular vagus nerve stimulation (taVNS) in 90 patients with Disorders of Consciousness (DoC) due to traumatic brain injury, using various assessment methods including the Coma Recovery Scale-Revised (CRS-R) and brain imaging techniques over a 40-day intervention period.

The research aims to clarify the mechanism of taVNS in promoting consciousness recovery and will also monitor adverse effects, making it a comprehensive approach to understanding this non-invasive treatment's potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of transcutaneous auricular vagus nerve stimulation on patients with disorders of consciousness: A study protocol. Cheng, L., Sun, L., Xu, L., 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 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]

Citations

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

Randomized trial of transcutaneous auricular vagus nerve ... In our study, we observed behavioral improvement and brain activity in patients receiving sensory stimulation intervention (28). New investigations have ...

2. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1323079/full

a sham-controlled randomized double-blind clinical trial The findings of this study suggest that taVNS may serve as a potentially effective and safe intervention for facilitating the restoration of consciousness.

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

Potential roles of vagus nerve stimulation on traumatic ... Smith and colleagues were the first group to demonstrate that VNS therapy enhanced motor function and cognitive recovery in experimental-TBI rats (Smith et al., ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10618368/

Transcutaneous auricular vagus nerve stimulation in the ... Studies on TBI-related DOC patients have shown promising results regarding the effectiveness of taVNS in promoting consciousness recovery.

5. 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.

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

Transcutaneous Vagus Nerve Stimulation in Patients With ... Controlled studies are needed to clarify whether tVNS has a potential to promote recovery of consciousness following severe TBI. Section snippets. INTRODUCTION.

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 ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2020/8841752

Effect and Safety of Transcutaneous Auricular Vagus Nerve ... At the endpoint, the FMA-U, WMFT, and FIM scores were significantly higher than before treatment (P < 0.05), and there was a significantly ...