[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657877":3},{"organization":4,"outcomesModule":7,"designInfo":36,"detailedDescription":35,"studyPopulation":35,"armGroups":45,"interventions":69,"overallOfficials":85,"centralContacts":89,"locations":94,"responsibleParty":108,"collaborators":35,"id":112,"slug":113,"hasResults":114,"nctId":115,"briefTitle":116,"officialTitle":117,"acronym":118,"eligibilityCriteria":119,"healthyVolunteers":114,"sex":120,"minAge":121,"maxAge":122,"enrollmentInfo":123,"targetDuration":35,"studyType":126,"phases":127,"briefSummary":129,"conditions":130,"keywords":132,"overallStatus":141,"whyStopped":35,"lastUpdateSubmitDate":142,"lastUpdatePostDateStruct":143,"startDateStruct":146,"completionDateStruct":148,"leadSponsor":150,"locationsCount":151},{"fullName":5,"class":6},"Privatklinik Meiringen","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":35},[9],{"measure":10,"description":11,"timeFrame":12},"Change From Baseline in Beck Depression Inventory-II (BDI-II) Score at Week 4","The Beck Depression Inventory-II (BDI-II) is a 21-item self-report instrument used to measure the severity of depressive symptoms. Each item is scored on a 4-point scale ranging from 0 to 3, yielding a total score from 0 to 63 points. Higher scores indicate greater severity of depression (0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; 29-63: severe depression). The change in the total score from baseline (Week 0) to completion of the 4-week intervention period will be analyzed.","Baseline (Week 0) and post-intervention (Week 4)",[14,18,22,25,28,31],{"measure":15,"description":16,"timeFrame":17},"Change From Baseline in Hamilton Depression Rating Scale (HAMD) Score at Week 4","The Hamilton Depression Rating Scale (HAMD) is a clinician-rated assessment tool used to quantify the severity of depressive symptoms in patients diagnosed with depression. The scale rates various depressive symptoms (including mood, feelings of guilt, suicide ideation, insomnia, anxiety, and somatic symptoms). Higher total scores reflect greater symptom severity. The change from baseline (Week 0) to completion of the 4-week intervention period will be analyzed.","Baseline (Week 0) and Week 4 (post-intervention)",{"measure":19,"description":20,"timeFrame":21},"Change From Baseline in Brief Symptom Checklist (BSCL) Score at Week 4 and 16","The Brief Symptom Checklist (BSCL) is a validated self-report questionnaire assessing current subjective psychological distress and psychiatric symptom burden across multiple dimensions (e.g., somatization, depression, anxiety). Items are rated on a 5-point Likert scale (0 = not at all, to 4 = extremely), with higher scores reflecting higher levels of subjective psychological distress. Changes from baseline to Week 4 and the 3-month follow-up (Week 16) will be evaluated.","Baseline (Week 0), Week 4 (post-intervention), and Week 16 (3-month follow-up)",{"measure":23,"description":24,"timeFrame":21},"Change From Baseline in General Self-Efficacy Scale (SWE) Score at Week 4 and Week 16","The General Self-Efficacy Scale (SWE \u002F Selbstwirksamkeitserwartung) is a self-report instrument assessing optimistic self-beliefs and confidence in coping with a variety of difficult demands and life challenges. Higher total scores indicate a greater perceived sense of personal self-efficacy and competence. Changes from baseline to Week 4 and the 3-month follow-up (Week 16) will be evaluated.",{"measure":26,"description":27,"timeFrame":17},"Change From Baseline in Heart Rate Variability (HRV) Parameters at Week 4","Heart rate variability will be measured using 24-hour ambulatory ECG recordings analyzed via Kubios HRV software. Evaluated autonomic regulation parameters include time-domain metrics: standard deviation of normal-to-normal intervals (SDNN, in ms) and root mean square of successive differences (RMSSD, in ms); and frequency-domain metrics: low-frequency power (LF, in ms²), high-frequency power (HF, in ms²), and total power (in ms²). Higher RMSSD and HF power reflect increased parasympathetic (vagal) tone. Change from baseline to post-intervention (Week 4) will be evaluated.",{"measure":29,"description":30,"timeFrame":17},"Change From Baseline in Serum Inflammatory Markers at Week 4","Fasting serum venous blood samples will be analyzed using high-sensitivity multiplex assays to evaluate pro- and anti-inflammatory cytokine concentrations and systemic inflammation. Specific biomarkers quantified include high-sensitivity C-reactive protein (hsCRP, in mg\u002FL), interleukin-6 (IL-6, in pg\u002FmL), interleukin-1 (IL-1, in pg\u002FmL), interleukin-4 (IL-4, in pg\u002FmL), and tumor necrosis factor-alpha (TNF-alpha, in pg\u002FmL). Changes in biomarker concentrations from baseline to Week 4 will be assessed.",{"measure":32,"description":33,"timeFrame":34},"Long-term Change in Beck Depression Inventory-II (BDI-II) Score at 3-Month Follow-Up","Assessment of the sustained treatment effect on depressive symptom severity using the 21-item BDI-II self-report total score (range 0-63, higher scores indicating more severe depression) at the 3-month follow-up compared to post-intervention (Week 4) and baseline (Week 0).","Week 16 (3 months post-intervention follow-up)",null,{"allocation":37,"interventionModel":38,"interventionModelDescription":35,"primaryPurpose":39,"observationalModel":35,"timePerspective":35,"maskingInfo":40},"RANDOMIZED","PARALLEL","TREATMENT",{"masking":41,"maskingDescription":42,"whoMasked":43},"SINGLE","the two groups of electrical stimulation are masked: Patients do not know if they belong to the group stimulating the Vagus Nerve or to the sham intervention group.",[44],"OUTCOMES_ASSESSOR",[46,52,58,64],{"label":47,"type":48,"description":49,"interventionNames":50},"Slow-Paced Breathing","EXPERIMENTAL","Participants perform a guided, device-free slow-paced breathing technique with prolonged exhalation (inhalation for 4 seconds, exhalation for 6 seconds) to stimulate the vagus nerve. The intervention is practiced for 20 minutes, 3 times daily (morning, afternoon, evening), on 5 days per week over a period of 4 weeks. Participants sit alone in a room and complete a daily protocol logging session duration, breathing frequency, and side effects. This intervention is administered in addition to standard inpatient psychiatric treatment (Treatment as Usual).",[51],"Behavioral: Slow-Paced Breathing",{"label":53,"type":54,"description":55,"interventionNames":56},"Transcutaneous Auricular Vagus Nerve Stimulation (tVNS)","ACTIVE_COMPARATOR","Participants receive non-invasive transcutaneous electrical stimulation of the auricular branch of the vagus nerve via a CE-certified ear electrode (tVNS device) placed in the cymba conchae of the left ear. Stimulation is applied for 20 minutes, 3 times daily, on 5 days per week over 4 weeks. Stimulation parameters include 25 Hz frequency, 250 µs pulse width, with alternating 28 s ON and 32 s OFF cycles at individually adjusted sensory thresholds (0.1-5.0 mA). Administered as an add-on to standard inpatient psychiatric treatment.",[57],"Device: Transcutaneous Auricular Vagus Nerve Stimulation (tVNS)",{"label":59,"type":60,"description":61,"interventionNames":62},"Sham Auricular Stimulation","SHAM_COMPARATOR","Participants receive identical-looking electrical stimulation applied to the left earlobe, an area free of cutaneous vagal innervation, serving as an active sensory placebo control. The session schedule (20 minutes, 3 times daily, 5 days per week for 4 weeks) and technical stimulus parameters match the active tVNS arm. Participants are blinded regarding whether they receive active or sham stimulation. Administered in addition to standard inpatient psychiatric treatment.",[63],"Device: Sham Auricular Electrical Stimulation",{"label":65,"type":6,"description":66,"interventionNames":67},"Treatment as Usual (TAU)","Participants receive the standard multimodal inpatient psychiatric and psychotherapeutic treatment program alone, including medical visits, psychopharmacotherapy, individual and group psychotherapy, and standard ward activities. To mitigate nocebo effects, participants are instructed to engage in standard relaxation\u002Fmindfulness elements offered on the ward and keep a daily log of time spent on relaxation exercises. No experimental breathing or electrical nerve stimulation is applied.",[68],"Other: Treatment as Usual (TAU)",[70,74,78,82],{"type":71,"name":47,"description":72,"armGroupLabels":73,"otherNames":35},"BEHAVIORAL","Guided slow-paced breathing technique with prolonged exhalation (4 seconds inhalation, 6 seconds exhalation, resulting in 6 breaths per minute) to stimulate the vagus nerve. Conducted for 20 minutes, 3 times daily, 5 days per week over a period of 4 weeks in a seated position, accompanied by daily protocol logging. Administered in addition to standard inpatient psychiatric care.",[47],{"type":75,"name":53,"description":76,"armGroupLabels":77,"otherNames":35},"DEVICE","Electrical nerve stimulation using a CE-certified class IIa medical device (tVNS® by tVNS Technologies GmbH). Stimulation is applied via custom ear electrodes to the cymba conchae of the left outer ear canal to transcutaneously activate vagal afferents. Parameters: 25 Hz frequency, 250 µs pulse duration, 28 s ON \u002F 32 s OFF cycle, intensity adjusted individually between 0.1 and 5.0 mA below pain threshold. Administered for 20 minutes, 3 times daily, 5 days per week over 4 weeks as an add-on to standard inpatient care.",[53],{"type":75,"name":79,"description":80,"armGroupLabels":81,"otherNames":35},"Sham Auricular Electrical Stimulation","Sham sensory control using identical stimulation parameters (25 Hz, 250 µs pulses, 28 s ON \u002F 32 s OFF) and device setup as active tVNS, but the stimulation electrode is attached to the left earlobe, a region devoid of vagal innervation. Conducted for 20 minutes, 3 times daily, 5 days per week for 4 weeks in addition to standard inpatient care.",[59],{"type":6,"name":65,"description":83,"armGroupLabels":84,"otherNames":35},"Standard multimodal inpatient psychiatric and psychotherapeutic treatment program including medication, psychotherapy, and clinical ward routine, accompanied by daily logging of relaxation exercises.",[65],[86],{"name":87,"affiliation":5,"role":88},"Elisabeth M Balint, PD Dr. med.","PRINCIPAL_INVESTIGATOR",[90],{"name":87,"role":91,"phone":92,"phoneExt":35,"email":93},"CONTACT","+41339728246","elisabeth.balint@privatklinik-meiringen.ch",[95],{"facility":5,"status":35,"city":96,"state":35,"zip":97,"country":98,"countryCode":99,"cosmosGeoPoint":100,"geoPoint":105,"contacts":106},"Meiringen","3860","Switzerland","CH",{"type":101,"coordinates":102},"Point",[103,104],8.1872,46.72709,{"lat":104,"lon":103},[107],{"name":87,"role":91,"phone":92,"phoneExt":35,"email":93},{"type":109,"investigatorFullName":110,"investigatorTitle":111,"investigatorAffiliation":5,"oldNameTitle":35,"oldOrganization":35},"SPONSOR_INVESTIGATOR","Elisabeth Balint","Principal Investigator","100657877","slow-paced-breathing-and-electrical-vagus-nerve-stimulation-as-add-on-treatments-for-depression-100657877",false,"NCT07844733","Slow-Paced Breathing and Electrical Vagus Nerve Stimulation as Add-on Treatments for Depression","Add-on Therapy of Depression Using Vagus Nerve Stimulation","Add-Vagus","Inclusion Criteria:\n\n* Inpatient psychiatric admission at Privatklinik Meiringen\n* Clinical primary diagnosis of at least a moderate depressive episode\n* Beck Depression Inventory-II (BDI-II) score of at least 20 at admission\n* Age between 18 and 60 years\n* Written informed consent prior to study participation\n* Ability to understand the study procedures and give informed consent\n\nExclusion Criteria:\n\n* Active substance use disorder \u002F addiction\n* Current psychosis\n* Bipolar disorder\n* Borderline personality disorder\n* Current malignancy\n* Multiple sclerosis\n* Presence of a cardiac pacemaker\n* Known or confirmed pregnancy\n* Body Mass Index (BMI) greater than 35 kg\u002Fm²\n* Current treatment with, or planned administration during the hospital stay of, ketamine or electroconvulsive therapy (ECT)","ALL","18 Years","60 Years",{"count":124,"type":125},160,"ESTIMATED","INTERVENTIONAL",[128],"NA","Depression is a common mental health condition, and standard psychiatric therapies do not always lead to satisfactory recovery. As a result, there is an urgent need for effective, complementary treatments.\n\nThe vagus nerve is the main component of the parasympathetic nervous system, which regulates bodily rest and calms inflammatory responses. In clinical depression, vagus nerve activity is often reduced, and low-grade inflammation is frequently observed. While electrical stimulation of the vagus nerve via surgically implanted devices has been shown to reduce depressive symptoms, its invasive nature carries risks. Non-invasive alternatives-such as slow-paced breathing exercises or gentle transcutaneous electrical stimulation at the outer ear-offer promising ways to stimulate this nerve safely without surgery.\n\nThe main purpose of this clinical study is to evaluate whether slow-paced breathing is an effective add-on therapy to reduce depressive symptoms in hospitalized patients compared to standard multimodal psychiatric treatment. Additionally, the study investigates whether the effects of slow-paced breathing are comparable to transcutaneous auricular vagus nerve stimulation (tVNS) and whether they differ from a sham (placebo) stimulation.\n\nA total of 160 adult inpatients with at least a moderate depressive episode will be randomly assigned to one of four groups during their hospital stay:\n\nGroup 1 (Slow-Paced Breathing): Participants practice a guided, slow-paced breathing technique (inhaling for 4 seconds, exhaling for 6 seconds) for 20 minutes, 3 times daily, 5 days per week over 4 weeks.\n\nGroup 2 (Electrical Vagus Nerve Stimulation): Participants receive non-invasive electrical stimulation to the outer ear canal using a certified medical device (tVNS) for 20 minutes, 3 times daily, 5 days per week over 4 weeks.\n\nGroup 3 (Sham Stimulation): Participants receive identical-looking electrical stimulation applied to the earlobe (an area lacking vagal nerve fibers) on the same schedule, serving as an active control. Participants do not know whether they receive active or sham stimulation.\n\nGroup 4 (Treatment as Usual): Participants receive the standard multimodal inpatient psychiatric treatment program alone, alongside daily logging of relaxation and mindfulness activities.\n\nAll participants continue to receive standard psychiatric care. Depressive symptoms are assessed using the Beck Depression Inventory-II (BDI-II) and the Hamilton Depression Rating Scale. In addition, heart rate variability (HRV) via a 24-hour recording and blood inflammatory markers (such as IL-6 and CRP) are measured before and after the 4-week intervention period to explore the physiological mechanisms of vagus activation. A follow-up questionnaire is completed after 3 months to assess long-term outcomes.",[131],"Depression - Major Depressive Disorder",[133,47,134,135,136,137,138,139,140],"Vagus Nerve Stimulation","Transcutaneous Vagus Nerve Stimulation","tVNS","Heart Rate Variability","HRV","Inpatient Psychiatry","Inflammation","Non-invasive Neuromodulation","NOT_YET_RECRUITING","2026-09-29",{"date":144,"type":145},"2026-10-02","ACTUAL",{"date":147,"type":125},"2026-11",{"date":149,"type":125},"2030-09",{"name":110,"class":6},1]