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).

Официальное название

LasaiOn: An Intervention Program to Reduce Emotional Distress

Обзор

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.

Подробное описание

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.

Вмешательства

• Комбинированный продукт 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 a

Первичные конечные точки

• State anxiety score [Срок оценки: From baseline (day 1) to post-intervention (day 5)]
• Depressive symptom score [Срок оценки: From baseline (day 1) to post-intervention (day5)]
• WHO-5 well-being score [Срок оценки: From baseline (day 1) to post-intervention (day 5)]
• Change in RMSSD [Срок оценки: from baseline (day 1) to post-intervention (day 5)]
• Change in skin conductance level [Срок оценки: From baseline (day 1) to post-intervention (day 5)]
• Change in startle response amplitude [Срок оценки: From baseline (day 1) to post-intervention (day 5)]
• Change in frontal midline theta band power at Fz [Срок оценки: from baseline (day 1) to post-intervention (day 5)]
• Change in frequency of intrusive-thought-related lexical occurrences [Срок оценки: from baseline (day 1) to post-intervention (day 5)]
• Change in SDNN [Срок оценки: From baseline (day 1) to post-intervention (day 5)]
• Change in high-frequency power [Срок оценки: From baseline (day 1) to post-intervention (day 5)]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Простое слепое

Основная цель

Фундаментальное исследование

Центры проведения

Испания · 1 центр

• Euskal Herriko Unibertsitatea — San Sebastián

Публикации

• Zhang Y, Lin P, Wang R, Zhou J, Xu X, Jiang W, Pu X, Ge S. Insula-Medial Prefrontal Cortex Functional Connectivity Modulated by Transcutaneous Auricular Vagus Nerve Stimulation: An fMRI Study. IEEE J Biomed Health Inform. 2024 Oct;28(10):5962-5970. doi: 10.1109/JBHI.2024.3423019. Epub 2024 Oct 3. PMID 38963749
• Dormal V, Vermeulen N, Mejias S. Is heart rate variability biofeedback useful in children and adolescents? A systematic review. J Child Psychol Psychiatry. 2021 Dec;62(12):1379-1390. doi: 10.1111/jcpp.13463. Epub 2021 Jun 21. PMID 34155631
• Tian QQ, Cheng C, Yin ZX, Yuan YY, Wang C, Zeng X, Sun JB, Yang Q, Yang XJ, Qin W. Combined transcutaneous auricular vagus stimulation (taVNS) with 0.1Hz slow breathing enhances insomnia treatment efficacy: A pilot study. Brain Stimul. 2024 Jan-Feb;17(1):4-6. doi: 10.1016/j.brs.2023.11.015. Epub 2023 Nov 30. No abstract available. PMID 38042286
• Napadow V, Edwards RR, Cahalan CM, Mensing G, Greenbaum S, Valovska A, Li A, Kim J, Maeda Y, Park K, Wasan AD. Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation. Pain Med. 2012 Jun;13(6):777-89. doi: 10.1111/j.1526-4637.2012.01385.x. Epub 2012 May 8. PMID 22568773
• McAllister-Williams RH, Sousa S, Kumar A, Greco T, Bunker MT, Aaronson ST, Conway CR, Rush AJ. The effects of vagus nerve stimulation on the course and outcomes of patients with bipolar disorder in a treatment-resistant depressive episode: a 5-year prospective registry. Int J Bipolar Disord. 2020 May 2;8(1):13. doi: 10.1186/s40345-020-0178-4. PMID 32358769
• Kim AY, Marduy A, de Melo PS, Gianlorenco AC, Kim CK, Choi H, Song JJ, Fregni F. Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Sci Rep. 2022 Dec 21;12(1):22055. doi: 10.1038/s41598-022-25864-1. PMID 36543841
• Thabrew H, Ruppeldt P, Sollers JJ 3rd. Systematic Review of Biofeedback Interventions for Addressing Anxiety and Depression in Children and Adolescents with Long-Term Physical Conditions. Appl Psychophysiol Biofeedback. 2018 Sep;43(3):179-192. doi: 10.1007/s10484-018-9399-z. PMID 29946920
• Goessl VC, Curtiss JE, Hofmann SG. The effect of heart rate variability biofeedback training on stress and anxiety: a meta-analysis. Psychol Med. 2017 Nov;47(15):2578-2586. doi: 10.1017/S0033291717001003. Epub 2017 May 8. PMID 28478782

Идентификаторы

NCT: NCT07498881 · M10/2026/055. March 2, 2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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