Healthy Adult Participants
Conditions
Keywords
Vagal Nerve Stimulation
Brief summary
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.
Interventions
DEVICEVagal Nerve Stimulation
Transcutaneous Auricular Vagal Nerve Stimulation
DEVICESham stimulation
Sham stimulation with a non-conducting electrode
Sponsors
Daniel Keszthelyi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neuroendocrine stress response | 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
| Measure | Time frame | Description |
|---|---|---|
| Subjective stress response | 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). |
| Cardiovascular stress response - blood pressure | 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. |
| Autonomic stress response: heart rate variability | 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. |
| Electrodermal stress response: skin conductance | 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). |
| Anxiety symptoms | 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). |
| Depressive symptoms | 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). |
| Personality traits | 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. |
| Adverse events | Assessed during one single test day, from pre-intervention baseline to post-MAST assessment (approximately 2-3 hours) | Number and severity of adverse events |
Countries
Netherlands
Contacts
PRINCIPAL_INVESTIGATORDaniel Keszthelyi, MD, PhD
Maastricht University Medical Center
Outcome results
None listed