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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:
Participants will be randomly assigned to either the taVNS or sham stimulation group, administered 30 minutes before the MAST.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Transcutaneous Auricular Vagal Nerve Stimulation | Active Comparator | Transcutaneous auricular vagal nerve stimulation, for 30 minutes |
|
| Sham stimulation | Placebo Comparator | Sham stimulation with a non-conducting electrode, for 30 minutes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Device | Transcutaneous Auricular Vagal Nerve Stimulation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Neuroendocrine stress response | 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. | Assessed during one single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours) |
| Measure | Description | Time Frame |
|---|---|---|
| Subjective stress response | 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daniel Keszthelyi, MD, PhD | Maastricht University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maastricht University | Maastricht | Limburg | 6229ER | Netherlands |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 17, 2024 | May 29, 2026 | Prot_000.pdf |
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| ID | Term |
|---|---|
| D055536 | Vagus Nerve Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
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| Sham stimulation | Device | Sham stimulation with a non-conducting electrode |
|
| Assessed during one single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours) |
| Cardiovascular stress response - blood pressure | 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. | Assessed during one single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours) |
| Autonomic stress response: heart rate variability | 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. | Assessed during a single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours) |
| Electrodermal stress response: skin conductance | 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). | Assessed during a single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours) |
| Anxiety symptoms | 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). | Assessed once during the screening visit, prior to the experimental test day |
| Depressive symptoms | Depressive symptoms assessed using the Patient Health Questionnaire-9 (PHQ-9; total score range: 0-27, with higher scores indicating greater depressive symptom severity). | Assessed once during the screening visit, prior to the experimental test day |
| Personality traits | 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. | Assessed once during the screening visit, prior to the experimental test day |
| Adverse events | Number and severity of adverse events | Assessed during one single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours) |