Adult
Conditions
Keywords
slow, paced breathing, transauricualr vagus nerve stimulation
Brief summary
The goal of this clinical trial is to evaluate whether the LasaiON program, which combines transcutaneous auricular vagus nerve stimulation (taVNS) with breathing supported by heart rate variability biofeedback (HRV-B; emWave), reduces emotional distress and improves stress-regulation processes in adults. The study will also assess the safety, tolerability, and feasibility of the intervention. The main questions it aims to answer are: 1. Does the LasaiON program reduce emotional distress in adults? 2. What physiological, psychological, and verbal-cognitive changes are observed following the intervention? 3. What discomforts, adverse effects, or tolerability issues do participants experience during the program? Researchers will use a prospective 2 × 2 factorial randomized controlled design to examine the effects of stimulation condition (active taVNS vs. sham taVNS) and training condition (active HRV-biofeedback vs. control training), as well as their potential interaction. Participants will be randomly allocated in equal proportions (1:1:1:1) to one of four groups: sham taVNS + control training, sham taVNS + HRV-biofeedback, active taVNS + control training, or active taVNS + HRV-biofeedback. Participants will: * undergo baseline assessments on Day 1 before the intervention; * complete 5 consecutive daily 60-minute sessions according to group allocation; * undergo post-intervention assessments on Day 5 after the final session; * complete psychometric, physiological, and verbal-cognitive assessments, including STAI, HAM-D, WHO-5, EEG, skin conductance, startle response, heart rate variability measures derived using Kubios HRV Premium, and daily five-word reports with valence ratings analyzed using IRaMuTeQ; * have adherence and tolerability recorded at each session using a checklist.
Detailed description
LasaiON is an evidence-informed, multimodal self-regulation program designed to reduce emotional distress and strengthen stress-regulation skills by combining transcutaneous auricular vagus nerve stimulation (taVNS) with breathing supported by heart-rate variability biofeedback (HRV-B; emWave). The study is designed to evaluate the effects of stimulation condition and training condition on psychophysiological, psychological, and verbal-cognitive outcomes in adults. This study is a prospective randomized controlled trial with a 2 × 2 factorial design. The two experimental factors are stimulation condition (active taVNS vs. sham taVNS) and training condition (active HRV-biofeedback training vs. control training). Participants will be randomly allocated in equal proportions (1:1:1:1) to one of four groups: sham taVNS + control training, sham taVNS + HRV-biofeedback training, active taVNS + control training, or active taVNS + HRV-biofeedback training. This design will allow estimation of the main effects of stimulation and training, as well as their potential interaction. The intervention will be delivered over 5 consecutive days. Participants will complete one 60-minute session per day in an individual format under researcher supervision. Baseline assessments will be performed on Day 1 before the intervention begins, and post-intervention assessments will be performed on Day 5 after completion of the final session. During each session, participants will remain comfortably seated in front of a computer in a standardized setting. According to group allocation, they will receive active or sham taVNS and active HRV-biofeedback training or control training. The procedures are designed to be non-invasive and are expected to be well tolerated. Session delivery will follow a standardized protocol to ensure consistency across participants and conditions. Before each session, pre-session requirements will be checked. Participants will be asked to avoid alcohol and strenuous exercise in the previous 12 hours, to avoid caffeine and nicotine before the session, and to avoid substances or medications that may substantially alter autonomic nervous system functioning, in accordance with protocol requirements. If necessary, deviations or incidents affecting the session will be recorded. Psychometric, psychophysiological, and verbal-cognitive assessments will be collected at baseline and post-intervention. Psychometric measures will assess anxiety, depressive symptoms, and emotional well-being. Psychophysiological measures will include electroencephalographic activity (EEG), skin conductance, startle response, and heart rate variability (HRV). HRV will be recorded using the emWave system and analyzed using Kubios HRV Premium. Derived HRV measures will include RMSSD, SDNN, HF power, LF power, LF/HF ratio, PNS index, and SNS index. Verbal-cognitive assessment will include daily five-word self-reports describing the participant's current state, together with valence ratings, analyzed using IRaMuTeQ. In addition to baseline and post-intervention assessments, participants will complete a brief daily digital self-report during the intervention period. This record will include five words describing their current state and a valence rating for each word. These data are intended to capture subjective verbal-cognitive changes across the intervention period using a standardized and minimally burdensome procedure. Adherence, tolerability, and safety will be monitored throughout the study. At each session, researchers will record session completion, duration, deviations, and any relevant incidents. Participants will complete a brief checklist assessing comfort, tolerability, ease of use, and any discomfort associated with the assigned procedures. Any adverse events, unusual sensations, interruptions, or reasons for withdrawal will be documented systematically. Recruitment will be continuous, with sequential enrollment expected over approximately 24 months. All sessions and assessments will be conducted at the Faculty of Psychology, Ibaeta Campus, University of the Basque Country (UPV/EHU). The study is conducted under the supervision of the research team led by Ainara Aranberri Ruiz, and all study procedures will be carried out confidentially and in accordance with applicable ethical requirements.
Interventions
COMBINATION_PRODUCTLasaiON
Participants will complete one 60-minute session per day. After verification of pre-session requirements, the researcher will place the EEG cap and the HRV, EDA, and EMG sensors and obtain baseline measures. Depending on allocation, participants will receive either active taVNS through stimulation electrodes placed on the auricular target area or sham taVNS using the same device setup without active therapeutic stimulation. From minutes 5-35, participants will remain seated while physiological activity is continuously recorded and they view segmented material from Our Oceans. From minutes 35-50, those allocated to active HRV-biofeedback will use the Coherence Coach platform to learn and practice slow breathing at 6 breaths/min, whereas control participants will observe their physiological activity on screen without guided breathing training. Each night at home, intrusive thoughts will be recorded through a brief Google Forms self-report and later analyzed with IRaMuTeQ.
Sponsors
University of the Basque Country (UPV/EHU)
Parasym Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
This study uses a 2 × 2 factorial randomized controlled design to evaluate the independent and combined effects of stimulation and training. The two intervention factors are stimulation condition (active transcutaneous auricular vagus nerve stimulation \[taVNS\] vs. sham taVNS) and training condition (active heart rate variability biofeedback \[HRV-biofeedback\] vs. control training). Participants will be randomly assigned in equal proportions (1:1:1:1) to one of four parallel groups: sham taVNS + control training, sham taVNS + HRV-biofeedback, active taVNS + control training, or active taVNS + HRV-biofeedback. This model allows estimation of the main effects of each factor and their interaction. Assessments will be performed at baseline (Day 1, pre-intervention) and post-intervention (Day 5, after the final session).
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* Ability to provide written informed consent * Physically healthy, with no relevant uncontrolled medical condition * Availability to complete the 5-day study protocol (1 session/day), including baseline and post-intervention assessments * Intact external ear and suitability for electrode placement on the tragus and acquisition of study recordings (EEG, EDA, HRV)
Exclusion criteria
* History of cardiovascular disease, diabetes, or hypertension * Severe bradycardia * Active implanted electronic device (e.g., pacemaker, cochlear implant, neurostimulator) * History of vagus nerve transection surgery (cervical vagotomy) * Pregnancy * Current or past clinically significant psychiatric disorder * Current or past clinically significant neurological disorder * Use of CNS-active medication * Substance misuse, including nicotine or alcohol * Dermatitis, infection, or lesions of the ear that could interfere with electrode application * Ongoing treatment with medications that modulate autonomic nervous system activity or may alter psychophysiological measures (e.g., HRV, EDA, EEG)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| State anxiety score | From baseline (day 1) to post-intervention (day 5) | Change in state anxiety assessed with the State Anxiety subscale of the State-Trait Anxiety Inventory (STAI-State). Scores range from 20 to 80, with higher scores indicating greater anxiety. |
| Depressive symptom score | From baseline (day 1) to post-intervention (day5) | Change in depressive symptoms assessed with the 17-item Hamilton Depression Rating Scale (HAM-D). Scores range from 0 to 52, with higher scores indicating greater depressive symptom severity. |
| WHO-5 well-being score | From baseline (day 1) to post-intervention (day 5) | Change in emotional well-being assessed with the World Health Organization-Five Well-Being Index (WHO-5). Raw scores range from 0 to 25, with higher scores indicating better emotional well-being. |
| Change in RMSSD | from baseline (day 1) to post-intervention (day 5) | Change in heart rate variability assessed by the root mean square of successive differences (RMSSD) using Kubios HRV software. RMSSD reflects beat-to-beat variability in heart rate and is reported in milliseconds (ms). Higher values indicate greater vagally mediated heart rate variability, whereas lower values indicate lower vagally mediated heart rate variability. |
| Change in skin conductance level | From baseline (day 1) to post-intervention (day 5) | Change in physiological arousal assessed by skin conductance level, measured in microsiemens (µS). Higher values indicate greater sympathetic arousal. |
| Change in startle response amplitude | From baseline (day 1) to post-intervention (day 5) | Change in physiological reactivity assessed by the peak amplitude of the acoustic startle eyeblink response, recorded from the orbicularis oculi muscle using electromyography (EMG). Startle amplitude will be defined as the peak EMG response occurring within 20 to 150 milliseconds after startle probe onset relative to the mean 50-millisecond pre-probe baseline. Amplitude will be reported in microvolts (µV), with higher values indicating greater physiological reactivity. |
| Change in frontal midline theta band power at Fz | from baseline (day 1) to post-intervention (day 5) | Change in frontal midline theta band power at Fz, recorded using the 8-channel Unicorn Hybrid Black electroencephalography (EEG) system. EEG data will be acquired at 250 Hz per channel and analyzed as absolute spectral power in the theta frequency band (4-8 Hz). Theta band power will be reported in microvolts squared per hertz (µV²/Hz). Higher values indicate greater frontal midline theta band power. |
| Change in frequency of intrusive-thought-related lexical occurrences | from baseline (day 1) to post-intervention (day 5) | Change in intrusive thoughts assessed by counting prespecified intrusive-thought-related lexical occurrences in written self-reports using IRaMuTeQ text analysis software. Frequency will be reported as the number of intrusive-thought-related lexical occurrences per written self-report. A value of 0 indicates no intrusive-thought-related lexical occurrences, and higher values indicate greater intrusive-thought-related lexical content. |
| Change in SDNN | From baseline (day 1) to post-intervention (day 5) | Change in heart rate variability assessed by the standard deviation of normal-to-normal RR intervals (SDNN) using Kubios HRV software. SDNN reflects overall heart rate variability, including both short-term and longer-term components, and is reported in milliseconds (ms). Higher values indicate greater overall heart rate variability, whereas lower values indicate lower overall heart rate variability. |
| Change in high-frequency power | From baseline (day 1) to post-intervention (day 5) | Change in heart rate variability assessed by high-frequency (HF) power using Kubios HRV software. HF power reflects high-frequency heart rate variability and will be reported as absolute power in milliseconds squared (ms²). Higher values generally indicate greater vagally mediated, parasympathetic modulation of heart rate variability. |
| Change in low-frequency power | From baseline (day 1) to post-intervention (day 5) | Change in heart rate variability assessed by low-frequency (LF) power using Kubios HRV software. LF power reflects low-frequency heart rate variability and will be reported as absolute power in milliseconds squared (ms²). Higher values indicate greater low-frequency heart rate variability. |
| Change in LF/HF ratio | From baseline (day 1) to post-intervention (day 5) | Change in heart rate variability assessed by the ratio of low-frequency to high-frequency power (LF/HF) using Kubios HRV software. The LF/HF ratio will be reported as a unitless ratio. Higher values indicate a higher ratio of low-frequency to high-frequency power. |
| Change in PNS index | From baseline (day 1) to post-intervention (day 5) | Change in autonomic function, assessed using the parasympathetic nervous system (PNS) index obtained from Kubios HRV software. In Kubios, a value of 0 reflects autonomic activity comparable to the normative population mean; positive values indicate higher parasympathetic activity, whereas negative values indicate lower parasympathetic activity. |
| Change in SNS index | From baseline (day 1) to post-intervention (day 5 | Change in autonomic function assessed by the sympathetic nervous system (SNS) index using Kubios HRV software. In Kubios, a value of 0 indicates values comparable to the normal population average; positive values indicate above-average sympathetic activity, and negative values indicate below-average sympathetic activity. |
Countries
Spain
Contacts
CONTACTAinara Aranberri Ruiz, Ph.D.
Outcome results
None listed