Ear Stimulation for Acute Stress Disorder

(ASR Trial)

Overseen By Mary Heimann

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Spark Biomedical, Inc.

Must not be taking: Anti-anxiety, ADHD medications

Disqualifiers: PTSD, ADHD, Substance abuse, 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

Duration: 30-35 minutes

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently using anti-anxiety medications like Xanax or beta blockers, or medications for ADHD, you will need to stop taking them to participate in this trial.

What data supports the effectiveness of the treatment Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for Acute Stress Disorder?

Research shows that taVNS is safe and has been effective in treating conditions like depression, anxiety, and stress-related disorders. It has also been shown to reduce heart rate during stress, suggesting it might help manage acute stress responses. ^{1 2 3 4 5}

Is ear stimulation (taVNS) safe for humans?

Ear stimulation using taVNS is generally considered safe, with mild and temporary side effects like ear pain, headache, and tingling. Studies show no significant risk of severe adverse events compared to controls. ^{1 3 4 6 7}

How does the treatment transcutaneous auricular neurostimulation (taVNS) for acute stress disorder differ from other treatments?

Transcutaneous auricular neurostimulation (taVNS) is unique because it is a non-invasive treatment that uses low-intensity electrical currents applied to the ear to stimulate the vagus nerve, potentially affecting brain areas involved in stress response. Unlike many traditional treatments, it does not involve medication and has been shown to be safe with minimal side effects. ^{1 2 7 8 9}

What is the purpose of this trial?

The objective of this study is to test the effects of transcutaneous auricular neurostimulation (tAN) in treating or preventing performance degradation after an acute stressor.

Research Team

Philip Putnam, PhD

Principal Investigator

Battelle Memorial Institute

Navid Khodaparast, PhD

Principal Investigator

Spark Biomedical, Inc.

Eligibility Criteria

This trial is for individuals experiencing acute stress reactions, which may affect cognitive performance. Participants should be in good health with no current treatments for stress disorders.

Inclusion Criteria

I can physically and mentally participate in all study activities.

Participant is right-hand dominant

Proficient in the English language

Exclusion Criteria

History of substance abuse or drug dependence including nicotine and alcohol in the past 3 months

Participant is participating in another interventional trial within 90 days prior to or throughout duration of trial

I have participated in a stress-management program in the past month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Participants complete baseline performance tasks and are prepared for the stressor protocol

Approximately 1 hour

1 visit (in-person)

Treatment

Participants receive either active tAN or sham stimulation during the stressor protocol

30-35 minutes

1 visit (in-person)

Post-stressor Assessment

Participants complete post-stressor tasks and biomarker data is collected

Up to 3 hours

1 visit (in-person)

Follow-up

Participants are monitored for any delayed effects and data is analyzed

1-2 weeks

Treatment Details

Interventions

• Transcutaneous Auricular Neurostimulation

Trial Overview The study tests transcutaneous auricular neurostimulation (tAN) using an active device called Sparrow Hawk and a sham (placebo) version to see if it helps prevent cognitive decline after acute stress.

Participant Groups

Group I: Active tAN for Prophylactic Treatment Experimental Treatment 1 Intervention

Prophylactic Active participants will undergo 20 minutes of active tAN while remaining seated and idle. After stimulation, participants will proceed into the 20-minute stressor protocol.

Group II: Active tAN for Acute Treatment Experimental Treatment 1 Intervention

Acute Active participants will begin the stressor protocol immediately after baseline assessments. After a 5-min period of the stressor protocol without any intervention, active tAN treatment will be delivered concurrently for the remainder of the stressor protocol for a total of 20 minutes of stimulation and approximately 25 minutes of the stressor protocol.

Group III: Sham Stimulation for Acute Treatment Placebo Group 1 Intervention

Acute Sham participants will begin the stressor protocol immediately after baseline assessments. After a 5-min period of the stressor protocol without any intervention, sham stimulation will be delivered concurrently for the remainder of the stressor protocol for a total of 20 minutes of stimulation and approximately 25 minutes of the stressor protocol.

Group IV: Sham Stimulation for Prophylactic Treatment Placebo Group 1 Intervention

Prophylactic Sham participants will undergo 20 minutes of sham stimulation while remaining seated and idle. After stimulation, participants will proceed into the 20-minute stressor protocol.

Transcutaneous Auricular Neurostimulation is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Auricular Neurostimulation for:

• Chronic pain
• Opioid withdrawal
• Irritable bowel syndrome

Approved in European Union as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Chronic pain
• Temporomandibular disorders

Who Is Running the Clinical Trial?

Spark Biomedical, Inc.

Lead Sponsor

Trials

14

Recruited

560+

Battelle Memorial Institute

Collaborator

Trials

14

Recruited

1,800+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

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]

A pilot study involving 37 patients with major depression showed that non-invasive auricular transcutaneous electric nerve stimulation (tVNS) resulted in a significant improvement in depression symptoms as measured by the Beck Depression Inventory, with an average score decrease of 12.6 points compared to 4.4 points in the sham group.

While the Hamilton Depression Rating Scale did not show significant changes, this study is the first to suggest an antidepressant effect of tVNS, indicating potential for further research despite limitations like small sample size and the need for more robust testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. Hein, E., Nowak, M., Kiess, O., et al.[2021]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and effective neuromodulation therapy for a variety of conditions, including epilepsy, depression, and anxiety, indicating its broad therapeutic potential.

Despite its effectiveness, there is currently no standardization among taVNS devices, and further research is needed to clarify the relationship between stimulation parameters and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Wang, L., Wang, Y., Wang, Y., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive technique that stimulates the vagus nerve in the outer ear, potentially helping to treat pediatric neurodevelopmental and psychiatric disorders by addressing maladaptive neural plasticity.

Current literature suggests that taVNS may be a promising alternative treatment for conditions like autism spectrum disorder and ADHD, especially for children who do not respond to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic applications of transcutaneous auricular vagus nerve stimulation with potential for application in neurodevelopmental or other pediatric disorders. Zhu, S., Zhang, X., Zhou, M., et al.[2022]

In a study involving 24 healthy adults, transcutaneous auricular vagus nerve stimulation (taVNS) was found to significantly reduce the initial heart rate increase during a cold pressor test, suggesting a potential calming effect on the body's stress response.

While taVNS showed a difference in heart rate response compared to sham stimulation, there were no significant differences in subjective feelings of anxiety, stress, or pain, indicating that while taVNS may affect physiological responses, it does not necessarily alter perceived stress levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Attenuates Early Increases in Heart Rate Associated With the Cold Pressor Test. Austelle, CW., Sege, CT., Kahn, AT., 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]

Transcutaneous auricular Vagus Nerve Stimulation (taVNS) can be optimized by varying electrode designs, which significantly affects the sensitivity and selectivity of nerve activation in different regions of the ear, as shown through a detailed anatomical model and finite element analysis.

The study found that smaller electrodes increase the electric field strength for a given current, allowing for more targeted stimulation of specific ear regions, which is crucial for enhancing the efficacy of taVNS in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). Kreisberg, E., Esmaeilpour, Z., Adair, D., et al.[2023]

Auricular stimulation (AS) has been shown to significantly reduce heart rate (HR) and alter heart rate variability (HRV) by decreasing the LF/HF ratio, indicating increased vagal activity, based on a systematic review of 78 trials.

The reduction in HR from AS is considered clinically safe, with only minor side effects reported, suggesting potential for further research into its use for managing conditions like tachycardia or autonomic imbalance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of auricular stimulation -a systematic review and meta-analysis of randomized controlled clinical trials. Hua, K., Cummings, M., Bernatik, M., et al.[2023]

In a study involving 26 subjects, simultaneous stimulation of the cymba and concha (CC) areas of the ear using extra-large electrodes was found to be the most effective for eliciting vagus somatosensory evoked potentials (VSEP), indicating strong neuromodulation effects.

The research demonstrated that the earlobe is not an effective target for taVNS, and using larger electrodes not only increased the amplitude of the response but also made the stimulation more comfortable for participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of different vagus nerve stimulation anatomical targets in the ear by vagus evoked potential responses. de Gurtubay, IG., Bermejo, P., Lopez, M., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Austria pubmed.ncbi.nlm.nih.gov

Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic applications of transcutaneous auricular vagus nerve stimulation with potential for application in neurodevelopmental or other pediatric disorders. [2022]

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

Transcutaneous Auricular Vagus Nerve Stimulation Attenuates Early Increases in Heart Rate Associated With the Cold Pressor Test. [2023]

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

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

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

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of auricular stimulation -a systematic review and meta-analysis of randomized controlled clinical trials. [2023]

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

Evaluation of different vagus nerve stimulation anatomical targets in the ear by vagus evoked potential responses. [2021]