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Completed

NCT Number: NCT07628842

Exploring the Effect of taVNS on the Acute Stress Responses

This single-center randomized controlled trial aims to investigate the effects of transcutaneous auricular vagus nerve stimulation on the acute stress responses.

The primary aim of this study is to assess the efficacy of taVNS in mitigating the acute stress response induced by the Maastricht Acute Stress Task (MAST) among healthy subjects, measured by cortisol levels in saliva samples.

Secondary objectives include:

* Evaluating taVNS's potential to counteract stress-induced sympathetic activation and thereby alleviate stress-related effects, including negative affect, as measuring using the I-PANAS-SF questionnaire, and feelings of stress, pain, and unpleasantness, as measured with 0-100 Visual Analog Scales (VAS) * Assessing its impact on autonomic outflow parameters, using a blood pressure monitor for blood pressure, and a FitBit smartwatch for heart rate variability, and Shimmer3 GSR sensor for heart rate variability and skin conductance. * Evaluating the relationship between stress responses and affective symptoms and personality traits, utilizing the Generalized Anxiety Disorder 7-Item Scale (GAD-7), Patient Health Questionnaire (PHQ-9), and the Big Five Inventory (BFI).

Participants will be randomly assigned to either the taVNS or sham stimulation group, administered 30 minutes before the MAST.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Maastricht University

Maastricht, Limburg, 6229ER, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy participants (defined as those without a pre-existing medical comorbidity)
  • Aged between 18-65 years
  • Ability to understand and speak the Dutch language.

Exclusion criteria

  • Medical history or condition affecting the cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, haematologic/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric systems, as well as prior major surgeries or ongoing laboratory abnormalities that could potentially limit participation or completion of the study protocol;
  • Any use of medication, especially those that may influence the autonomic nervous system or the hypothalamus-pituitary-adrenal axis (e.g., beta-agonists or corticosteroids), with the exception of contraceptives and paracetamol;
  • Current or lifetime psychopathology (including PHQ-9 and GHD-7 scores > 10);
  • Substance abuse (including excessive alcohol consumption);
  • Smoking;
  • Pregnancy, lactation, or intention to become pregnant during the study period;
  • Use of devices (e.g., cochlear implants) or other reasons (e.g. wounds, permanent ear-piercing) which complicate the use of the tVNS device;
  • Participation in another clinical study in which the MAST was used;
  • Administration of investigational drugs or participation in any scientific intervention study that might interfere with this study (to be determined by the principal investigator) within 180 days preceding the commencement of the study;
  • Students and employees of Maastricht University are not precluded from participation, unless they have a direct personal, professional or hierarchical position with regards to any of the study team members or their department.

Treatment and study plan

Vagal nerve stimulation

Device

Transcutaneous Auricular Vagal Nerve Stimulation

Sham stimulation

Device

Sham stimulation with a non-conducting electrode

Primary outcomes

  1. Neuroendocrine stress response

    Time frame: Assessed during one single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours)

    A significant reduction in the neuroendocrine stress response triggered by the MAST following taVNS or sham treatment, assessed through saliva cortisol samples, with a defined threshold of a 35% decrease.

Secondary outcomes

  1. Subjective stress response

    Time frame: Assessed during one single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours)

    Subjective stress responses to the MAST following taVNS or sham treatment, assessed using the negative affect subscale of the International Positive and Negative Affect Schedule Short Form (I-PANAS-SF; total score range: 5-25, with higher scores indicating greater negative affect) and 0-100 Visual Analog Scales (VAS) for stress, pain, and unpleasantness (0=not at all, 100=extremely; higher scores indicate greater perceived stress, pain, or unpleasantness).

  2. Cardiovascular stress response - blood pressure

    Time frame: Assessed during one single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours)

    Changes in systolic and diastolic blood pressure responses to the Maastricht Acute Stress Test (MAST) following transcutaneous auricular vagus nerve stimulation (taVNS) or sham stimulation, assessed in mmHg. Blood pressure was measured four times.

  3. Autonomic stress response: heart rate variability

    Time frame: Assessed during a single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours)

    Changes in heart rate variability responses to the Maastricht Acute Stress Test (MAST) following transcutaneous auricular vagus nerve stimulation (taVNS) or sham stimulation, assessed using Fitbit and Shimmer3 GSR. Heart rate variability was measured continuously during the test day.

  4. Electrodermal stress response: skin conductance

    Time frame: Assessed during a single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours)

    Changes in skin conductance responses to the Maastricht Acute Stress Test (MAST) following transcutaneous auricular vagus nerve stimulation (taVNS) or sham stimulation, assessed in microsiemens (µS).

  5. Anxiety symptoms

    Time frame: Assessed once during the screening visit, prior to the experimental test day

    Anxiety symptoms assessed using the Generalized Anxiety Disorder-7 questionnaire (GAD-7; total score range: 0-21, with higher scores indicating greater anxiety symptom severity).

  6. Depressive symptoms

    Time frame: Assessed once during the screening visit, prior to the experimental test day

    Depressive symptoms assessed using the Patient Health Questionnaire-9 (PHQ-9; total score range: 0-27, with higher scores indicating greater depressive symptom severity).

  7. Personality traits

    Time frame: Assessed once during the screening visit, prior to the experimental test day

    Personality traits assessed using the Big Five Inventory-44 (BFI-44). The BFI-44 measures five personality domains (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to Experience). Each domain score is computed as a sum or mean of item responses on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree), with higher scores indicating greater expression of the respective personality trait.

  8. Adverse events

    Time frame: Assessed during one single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours)

    Number and severity of adverse events

Sponsors and collaborators

Lead sponsor

Daniel Keszthelyi

Other

Registry information

Official study title

Exploring the effect of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on the Acute Stress Responses: a Double-blind Randomized Controlled Trial

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Jun 5, 2026
Registry last updated
Jun 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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