An interventional study of LasaiON in Adult, sponsored by University of the Basque Country (UPV/EHU). Not yet recruiting at 1 site in Spain. Per ClinicalTrials.gov, last updated 2026-03-27.
Sponsored by University of the Basque Country (UPV/EHU) · Not applicable, Interventional, and Basic science
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:
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:
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.
Exclusion Criteria:
Participants assigned to this arm will receive sham taVNS together with active HRV-biofeedback training over 5 consecutive intervention days, with one supervised 60-minute session per day. In each session, participants will sit comfortably in front of a computer. A sham taVNS device will be positioned at the tragus but will not deliver active electrical stimulation, while heart rate variability biofeedback will be provided through an ear sensor connected to the emWave platform. Sessions will include a brief pre-session checklist, fitting of psychophysiological recording equipment (EEG, HRV, EDA/EMG), a short quiet baseline, approximately 10 minutes of slow paced breathing (\~6 breaths/min) supported by Coherence Coach, followed by post-session tolerability/comfort ratings. This arm is designed to isolate the effect of active HRV-biofeedback training in the absence of active taVNS.
Combination Product: LasaiON
Participants assigned to this arm will receive active transcutaneous auricular vagus nerve stimulation (taVNS) combined with control training across five consecutive intervention days, with one supervised 60-minute session per day. During each session, participants will be seated comfortably in front of a computer. Active taVNS will be delivered at the tragus, while the training component will consist of a control condition without the Coherence Coach application, rather than active HRV biofeedback. Sessions will include a brief pre-session checklist, fitting of psychophysiological recording equipment (EEG, HRV, and EDA/EMG), a short resting baseline, and post-session ratings of tolerability and comfort. This arm is intended to isolate the effect of active taVNS in the absence of active HRV biofeedback training.
Combination Product: LasaiON
Participants assigned to this arm will receive the full active LasaiON intervention over 5 consecutive intervention days, with one supervised 60-minute session per day. In each session, participants will sit comfortably in front of a computer while receiving active transcutaneous auricular vagus nerve stimulation (taVNS) at the tragus together with active heart rate variability biofeedback (HRV-biofeedback) breathing training supported by the emWave platform. Sessions will include a brief pre-session checklist, fitting of psychophysiological recording equipment (EEG, HRV, EDA/EMG), a short quiet baseline, delivery of both active intervention components, and post-session tolerability/comfort ratings. This arm is designed to evaluate the combined effect of active taVNS and active HRV-biofeedback training and to determine whether their combination produces greater benefits than either component alone or than the fully control condition.
Combination Product: LasaiON
This control condition is delivered over 5 consecutive days, with one supervised 60-minute session per day, and is designed to match the active intervention in schedule, setting, and researcher contact without providing the active therapeutic components. Participants attend the sessions in the same standardized format, but the sham taVNS device placed at the tragus does not deliver active electrical stimulation, and the training condition does not include active HRV-biofeedback or the paced-breathing training intended to consolidate a respiratory rhythm of approximately 6 breaths per minute. This condition is intended to control for expectancy, procedural context, and time spent in session while withholding both active taVNS and active HRV-biofeedback training.
Combination Product: LasaiON
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.
State anxiety score
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.
Time frame: From baseline (day 1) to post-intervention (day 5)
Depressive symptom score
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.
Time frame: From baseline (day 1) to post-intervention (day5)
WHO-5 well-being score
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.
Time frame: From baseline (day 1) to post-intervention (day 5)
Change in RMSSD
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.
Time frame: from baseline (day 1) to post-intervention (day 5)
Change in skin conductance level
Change in physiological arousal assessed by skin conductance level, measured in microsiemens (µS). Higher values indicate greater sympathetic arousal.
Time frame: From baseline (day 1) to post-intervention (day 5)
Change in startle response amplitude
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.
Time frame: From baseline (day 1) to post-intervention (day 5)
Change in frontal midline theta band power at Fz
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.
Time frame: from baseline (day 1) to post-intervention (day 5)
Change in frequency of intrusive-thought-related lexical occurrences
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.
Time frame: from baseline (day 1) to post-intervention (day 5)
Change in SDNN
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.
Time frame: From baseline (day 1) to post-intervention (day 5)
Change in high-frequency power
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.
Time frame: From baseline (day 1) to post-intervention (day 5)
Change in low-frequency power
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.
Time frame: From baseline (day 1) to post-intervention (day 5)
Change in LF/HF ratio
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.
Time frame: From baseline (day 1) to post-intervention (day 5)
Change in PNS index
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.
Time frame: From baseline (day 1) to post-intervention (day 5)
Change in SNS index
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.
Time frame: From baseline (day 1) to post-intervention (day 5
Number of participants with adverse events
Number of participants who experience at least one adverse event during the 5-day intervention period. Adverse events will be recorded systematically at each session.
Time frame: At each session during the 5-day intervention period
Procedure-related discomfort score
Procedure-related discomfort assessed using an ad hoc Likert scale ranging from 0 to 5, where 0 indicates no discomfort and 5 indicates very severe discomfort. Higher scores indicate greater procedure-related discomfort.
Time frame: At each session during the 5-day intervention period
Number of participants who complete all intervention sessions
Number of participants who complete all planned LasaiON intervention sessions during the 5-day intervention period. Higher values indicate greater intervention completion.
Time frame: During the 5-day intervention period
Plan to share: No — Data will be anonymized and will not be shared with third parties. The dataset will be registered at the University of the Basque Country (UPV/EHU) under the following data-processing record, in accordance with the EU General Data Protection Regulation (GDPR; Regulation (EU) 2016/679): data-processing code TI0741-1471 ; name of the data-processing activity: LasaiON
This study is not yet recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of the Basque Country (UPV/EHU)