Exploring the Effect of taVNS on the Acute Stress Responses

NCT07628842 | Completed

• 1 other identifier: NL87188.068.24
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Adult Participants

Keywords

Vagal Nerve Stimulation

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (8)

• Subjective stress response

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

• Cardiovascular stress response - blood pressure

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

• Autonomic stress response: heart rate variability

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

• Electrodermal stress response: skin conductance

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

• Anxiety symptoms

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

Study Arms (2)

Transcutaneous Auricular Vagal Nerve Stimulation

ACTIVE COMPARATOR

Transcutaneous auricular vagal nerve stimulation, for 30 minutes

Device: Vagal Nerve Stimulation

Sham stimulation

PLACEBO COMPARATOR

Sham stimulation with a non-conducting electrode, for 30 minutes

Device: Sham stimulation

Interventions

Vagal Nerve Stimulation DEVICE

Transcutaneous Auricular Vagal Nerve Stimulation

Transcutaneous Auricular Vagal Nerve Stimulation

Sham stimulation DEVICE

Sham stimulation with a non-conducting electrode

Sham stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Daniel Keszthelyi: lead

Study Sites (1)

Maastricht University

Maastricht, Limburg, 6229ER, Netherlands

Location

MeSH Terms

Interventions

Vagus Nerve Stimulation

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Officials

• Daniel Keszthelyi, MD, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. D. Keszthelyi

Study Record Dates

• First Submitted: May 22, 2026
• First Posted: June 5, 2026
• Study Start: March 21, 2025
• Primary Completion: March 12, 2026
• Study Completion: March 12, 2026
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)