The goal of this clinical trial is to learn if transcutaneous auricular vagus nerve stimulation (taVNS) works to reduce perceived stress and psychological distress in university students with high distress levels. The main questions it aims to answer are:

• Does taVNS reduce perceived stress (measured by PSS-10) in university students with high psychological distress?
• Does taVNS reduce psychological distress (measured by K10) in university students with high psychological distress?
• Is the intervention feasible and tolerable for implementation in higher-education mental health support?

Researchers will compare taVNS (electrode placed on the left tragus) to a sham stimulation group (electrode placed on the left earlobe) to see if taVNS reduces stress and distress.

Participants will:

• Attend five consecutive daily 30-minute stimulation sessions
• Complete stress and distress questionnaires before the intervention, immediately after, and at 1-month follow-up
• Receive electrical stimulation at individually adjusted intensity using the Nurosym device (pulse width 250 µs, frequency 20 Hz).

Mental health is increasingly recognized as a core component of overall health, reflecting the capacity to regulate behavior, maintain daily functioning, and sustain satisfying interpersonal relationships. Chronic exposure to adverse circumstances, particularly prolonged stress, has been associated with mental health problems and contributes to the onset and maintenance of common psychological disorders.

University students are exposed to multiple risk stressors (psychological, academic, biological, lifestyle, social, and economic) associated with poorer well-being. The transition to higher education often coincides with entry into adulthood and is frequently described as a particularly demanding period in emotional and mental terms. Students commonly report high stress while adapting to academic demands that may exceed previously acquired skills and coping strategies. Stressors in this setting often include academic pressure, peer competition, ineffective time management, financial concerns, work-life conflicts, and mental overload from multiple responsibilities.

Sustained exposure to these stressors is associated with poorer learning performance, physical health problems, and sleep disturbances. High and persistent stress, especially when perceived as uncontrollable and excessive, is frequently associated with higher psychological distress among university students. In turn, psychological distress is associated with elevated anxiety and depressive symptoms, sleep problems, reduced self-esteem and self-efficacy, and in more severe presentations, with self-injury, suicidal ideation, substance use, and neglect of academic responsibilities.

International literature has reported high burden and, in some settings, worsening trends in university student mental health over the last decade, positioning it as a relevant public health concern. In the WHO World Mental Health International College Student Initiative, 93.7% of 20,842 students across 24 universities in nine countries experienced some level of stress. In Portugal, similar concerning patterns have been reported: at the University of Lisbon, one quarter of 7,756 students presented severe or very severe stress levels, and a further survey indicated that nearly half of 2,084 students reported psychological symptoms and about one quarter had considered suicide.

Multiple approaches have been used to address stress-related mental health problems in university students, including psychotropic medication, cognitive-behavioral therapy, mindfulness-based interventions, relaxation techniques, and biofeedback-based strategies. However, pharmacological approaches may be limited by side effects and other constraints, and many effective interventions require time, staffing, or infrastructure that can restrict scalability in academic settings. These limitations underscore the need to evaluate complementary interventions that are feasible, acceptable, and implementable in university contexts.

Intervention Rationale:

Non-invasive neuromodulation has emerged as a potential strategy for stress-related mental health problems. Neuromodulation broadly refers to the application of electrical, magnetic, vibratory, or ultrasonic stimuli to modify nervous system activity and regulate dysfunctional neural circuits. Within this domain, modulation of vagal pathways has received increasing attention because the vagus nerve contributes to autonomic balance by promoting parasympathetic activation and dampening sympathetic arousal, thereby supporting recovery after stress and emotional/physiological homeostasis. Disruption of this balance, marked by heightened sympathetic activation and reduced parasympathetic activity, has been associated with poorer physical and mental health outcomes.

Transcutaneous vagus nerve stimulation (tVNS) was developed as a less invasive alternative to implanted vagus nerve stimulation. Transcutaneous auricular vagus nerve stimulation (taVNS) targets the auricular branch of the vagus nerve using low-intensity electrical impulses applied to regions of the ear with dense vagal innervation, such as the tragus. By stimulating auricular vagal afferents, taVNS is proposed to engage stress and autonomic regulatory hubs (e.g., nucleus tractus solitarius, locus coeruleus), with downstream effects that may modulate autonomic stress-related physiology.

Consistent with this mechanistic rationale, taVNS has been investigated as a non-invasive strategy to reduce stress-related outcomes, including perceived stress and psychological distress. Available findings suggest potential benefits, but conclusions remain constrained by substantial heterogeneity in stimulation parameters, stimulation sites, and sham conditions. Brief, pragmatic protocols have yielded mixed but encouraging findings, including reductions in stress-related outcomes and anxiety in student samples, warranting further trials with standardized procedures and follow-up assessments. Importantly, evidence focused specifically on university students with elevated psychological distress remains limited, and many studies do not explicitly recruit or stratify participants using clinically meaningful distress thresholds.

Study Design:

This is a randomized, blinded clinical trial using convenience sampling of university students, randomly allocated to an experimental taVNS group or a sham (simulated stimulation) group. Assessments are conducted at three time points: pre-intervention (baseline), immediately post-intervention (after five sessions), and 1-month follow-up.

Participants:

Eligibility criteria include being a university student, aged ≥18 years, and assessed with high to very high levels of psychological distress (K10≥22). Exclusion criteria include psychotropic medication initiation or dose change within the last 3 months, substance dependence, current psychological or psychotherapeutic treatment, any formal mental disorder diagnosis, or contraindications for taVNS (e.g., pregnancy, history of dizziness or seizures, cochlear implants, ear plastic surgery, or auricular malformations). The study enrolled 40 participants, equally distributed across groups (n=20 per group).

Intervention Protocol:

The intervention consists of five consecutive daily 30-minute sessions delivered with the Nurosym device (preset pulse width 250 µs and frequency 20 Hz, with intensity adjusted to each participant's perception threshold). The only procedural difference between groups is electrode placement: in the taVNS group, the electrode is positioned on the left tragus, whereas in the sham group it is positioned on the left earlobe (a region with minimal vagal innervation).

Outcome Measures:

Perceived stress is assessed with the 10-item Perceived Stress Scale (PSS-10), scored 0 ("never") to 4 ("very often") and summed to a total score of 0-40, with higher scores indicating higher perceived stress. Psychological distress is assessed with the 10-item Kessler Psychological Distress Scale (K10), scored 1 ("never") to 5 ("always") with reference to the prior 30 days and summed to a total score of 10-50, with higher scores indicating higher distress. Internal consistency of the PSS-10 and K-10 will be evaluated at each time point using Cronbach's alpha.

A sociodemographic questionnaire is used to characterize the sample (age and sex) and to collect clinical information relevant to exclusion criteria (including medical comorbidities, psychotropic medication use, and participation in psychotherapeutic groups).

Procedures:

Recruitment is made via in-person classroom information sessions, and interested students receive a link to enroll. After providing informed consent, candidates complete the pre-intervention assessment protocol (sociodemographic questionnaire, PSS-10, and K10), and eligible participants are contacted by email to schedule sessions and randomly allocated to taVNS or sham by a draw. Before the first session, participants are re-asked about exclusion criteria to ensure ongoing eligibility.

After the fifth session, participants complete the post-intervention questionnaires (PSS-10 and K10) and are contacted by email 1 month later to complete the follow-up assessment.

After study completion and debriefing, participants originally assigned to the sham group were informed that they could, if they wished, receive active taVNS outside of the study procedures. This optional post-trial offer was not part of the clinical trial protocol, was not systematically documented as study data, and did not involve any formal cross-over within the trial.

Safety Monitoring:

Adverse events will be monitored before and after each session through visual inspection and participant self-report.

Statistical Analysis:

Analyses include internal consistency analyses (Cronbach's alpha), descriptive statistics, repeated-measures MANOVA with time (pre, post, follow-up) as the within-subject factor and group (taVNS vs sham) as the between-subject factor for two correlated dependent variables (PSS-10 and K10), followed by two repeated-measures ANOVAs (one per outcome) and Bonferroni-corrected pairwise comparisons across time points.

Ethics:

The study received approval from the institutional Ethics Committee (registration number 1328) and was conducted in accordance with the Declaration of Helsinki.

After the completion of the 1-month follow-up, participants originally assigned to the sham earlobe condition were offered optional taVNS with tragus placement outside the formal trial protocol.

Study Objectives:

This study aims to test whether a brief taVNS protocol reduces perceived stress and psychological distress in university students with high distress (K10 ≥ 22), assessed using the PSS-10 and K10 at baseline, post-intervention, and 1-month follow-up. The study also evaluates feasibility and tolerability to inform the translational potential of taVNS as a scalable adjunct within higher-education mental health support.

Inclusion Criteria:

• Being a university student
• Age ≥18 years
• High to very high levels of psychological distress (K10 score ≥22)

Exclusion Criteria:

• Psychotropic medication initiation or dose change within the last 3 months
• Substance dependence
• Current psychological or psychotherapeutic treatment
• Any formal mental disorder diagnosis
• Pregnancy
• History of dizziness or seizures
• Cochlear implants
• Ear plastic surgery
• Auricular malformations

Individual participant data (IPD) will not be shared because the informed consent obtained for this study did not include permission to share de-identified participant-level data with external researchers. If an ethics/IRB amendment and participant authorization (e.g., re-consent) are obtained in the future, the study team may update this record and make a de-identified dataset available under controlled access.

Days 1 through 5 (monitored before and after each intervention session)

Adverse events were assessed systematically before and after each session via visual inspection of the stimulation site by study personnel and structured open-ended questioning of participants regarding stimulation-related symptoms.

Limitations include the small sample size (N = 40), reliance on self-reports (PSS-10, K-10), predominantly female sample (82.5%), and self-reported mental disorder exclusion. While the earlobe condition provided a credible sham, its potential physiological activity may have reduced sensitivity to detect site-specific effects.

This is a blinded clinical trial where participants are not informed of their group allocation (taVNS vs sham). Both groups undergo identical procedures with the same stimulation device, parameters, and session duration; the only difference is electrode placement (tragus vs earlobe). Outcomes are assessed via self-report questionnaires completed by participants who remain blinded to group allocation.