Ignite Creation Date:
2025-12-24 @ 9:34 PM
Ignite Modification Date:
2025-12-25 @ 7:18 PM
Study NCT ID:
NCT07274332
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-12-10
First Post:
2025-11-27
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Frequency-Dependent Effects of Auricular Vagus Nerve Stimulation on Autonomic and Cardiovascular Parameters
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D053120', 'term': 'Respiratory Aspiration'}], 'ancestors': [{'id': 'D012120', 'term': 'Respiration Disorders'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT'], 'maskingDescription': 'Participants are blinded to the stimulation condition. The Pulsetto FIT™ device displays active lights and interface indicators in both sham and active frequencies, but delivers no current in the sham arm (0 Hz).\n\nThe investigator administering the stimulation is aware of the condition due to device programming requirements.'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'All participants receive each of the five stimulation conditions in randomized counterbalanced order (Williams Latin Square). Each visit includes a 10-minute tcVNS session and before/after physiological recordings. Washout between visits is ≥48 hours.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 36}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-12-22', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-11', 'completionDateStruct': {'date': '2026-03-15', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-11-27', 'studyFirstSubmitDate': '2025-11-27', 'studyFirstSubmitQcDate': '2025-11-27', 'lastUpdatePostDateStruct': {'date': '2025-12-10', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-12-10', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2026-01-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Heart Rate Variability (HRV) Changes (ΔRMSSD, ΔHF, ΔLF/HF)', 'timeFrame': 'Pre- vs Post-stimulation (5-min segments)(5-minute baseline, 5-minute stimulation, 5-minute post period)', 'description': 'HRV is recorded using a validated high-resolution heart rate monitor (Polar H10) during a 5-minute resting baseline (T0) and a 5-minute post-stimulation period (T2).\n\nThe following time- and frequency-domain parameters are analyzed: RMSSD, HF (ms²), and LF/HF ratio.\n\nArtefact correction is performed using standard HRV processing methods. Acute autonomic response is quantified by calculating change scores (Δ = post-pre) for each stimulation frequency.'}], 'secondaryOutcomes': [{'measure': 'Blood Pressure (SBP, DBP, MAP)', 'timeFrame': 'Pre- vs Post-stimulation (5-minute baseline, 5-minute stimulation, 5-minute post period)', 'description': 'Two readings are taken at each time point from the right arm with a validated automatic sphygmomanometer, and the average systolic, diastolic, and mean arterial pressure values are used for analysis.\n\nChanges are calculated as post-pre (Δ values) to assess the acute physiological effect of each stimulation frequency..'}, {'measure': 'Respiratory Rate (breaths per minute)', 'timeFrame': 'Pre- vs Post-stimulation (5-minute video segments) (5-minute baseline, 5-minute stimulation, 5-minute post period)', 'description': 'Respiratory rate is assessed by video-based thoracoabdominal motion tracking at baseline (T0) and after stimulation (T2).\n\nVideos are analyzed using Kinovea motion-tracking software, and a 1-minute stable segment is used to determine breaths per minute by counting inspiratory peaks.\n\nRespiratory changes are expressed as Δ values (post-pre) to account for individual differences and improve HRV interpretability.Respiratory rate is assessed by video-based thoracoabdominal motion tracking at baseline (T0) and after stimulation (T2).\n\nVideos are analyzed using Kinovea motion-tracking software, and a 1-minute stable segment is used to determine breaths per minute by counting inspiratory peaks.\n\nRespiratory changes are expressed as Δ values (post-pre) to account for individual differences and improve HRV interpretability.'}, {'measure': 'Discomfort Level (Visual Analog Scale, 0-10)', 'timeFrame': 'Pre- vs Post-stimulation (5-minute baseline, 5-minute stimulation, 5-minute post period)', 'description': 'Participants report their perceived discomfort level at baseline (T0) and immediately after stimulation (T2) using a 0-10 Visual Analog Scale (VAS).\n\nThe scale captures any sensory discomfort associated with tcVNS. Changes are calculated by subtracting the pre-stimulation score from the post-stimulation score (ΔVAS).'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Transcutaneous Cervical Vagus Nerve Stimulation', 'Neuromodulation', 'Non-invasive Vagus Stimulation', 'Parasympathetic Activation', 'Heart Rate Variability'], 'conditions': ['Vagus Nerve Stimulation', 'Autonomic Nervous System', 'Heart Rate', 'Blood Pressure', 'Respiration', 'Healthy Volunteers']}, 'referencesModule': {'references': [{'pmid': '35134082', 'type': 'RESULT', 'citation': 'Kranz S, Lukacs J, Bishop J, Block ME. Intergeneration transfer of diet patterns? Parental self-report of diet and their report of their young adult children with ASD. PLoS One. 2022 Feb 8;17(2):e0263445. doi: 10.1371/journal.pone.0263445. eCollection 2022.'}, {'pmid': '33839137', 'type': 'RESULT', 'citation': 'Alsoufi B. Curb Your Enthusiasm for the Ozaki Procedure in Small Children. Ann Thorac Surg. 2022 Jan;113(1):378-379. doi: 10.1016/j.athoracsur.2021.03.085. Epub 2021 Apr 8. No abstract available.'}, {'pmid': '31417453', 'type': 'RESULT', 'citation': 'Nordahl HM, Wells A. Metacognitive Therapy of Early Traumatized Patients With Borderline Personality Disorder: A Phase-II Baseline Controlled Trial. Front Psychol. 2019 Jul 30;10:1694. doi: 10.3389/fpsyg.2019.01694. eCollection 2019.'}, {'pmid': '11835542', 'type': 'RESULT', 'citation': 'Peuker ET, Filler TJ. The nerve supply of the human auricle. Clin Anat. 2002 Jan;15(1):35-7. doi: 10.1002/ca.1089.'}, {'pmid': '17081672', 'type': 'RESULT', 'citation': 'Grossman P, Taylor EW. Toward understanding respiratory sinus arrhythmia: relations to cardiac vagal tone, evolution and biobehavioral functions. Biol Psychol. 2007 Feb;74(2):263-85. doi: 10.1016/j.biopsycho.2005.11.014. Epub 2006 Nov 1.'}, {'pmid': '26831988', 'type': 'RESULT', 'citation': 'Zhang Y, Xiao S, Feng H, Zhang L, Zhou Z, Hu W. Self-interference cancellation using dual-drive Mach-Zehnder modulator for in-band full-duplex radio-over-fiber system. Opt Express. 2015 Dec 28;23(26):33205-13. doi: 10.1364/OE.23.033205.'}, {'pmid': '37867315', 'type': 'RESULT', 'citation': 'Fernandes TL, Viezzer Fernandes B, Jitumori C, Franco GCN. A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture. Am J Case Rep. 2023 Oct 23;24:e941144. doi: 10.12659/AJCR.941144.'}]}, 'descriptionModule': {'briefSummary': 'This randomized, sham-controlled, crossover study investigates the acute autonomic effects of transcutaneous cervical vagus nerve stimulation (tcVNS) applied at five different frequencies (0 Hz/sham, 10 Hz, 25 Hz, 50 Hz, 100 Hz) in healthy adults. The primary objective is to determine how stimulation frequency modulates heart rate variability (HRV), blood pressure, and respiratory rate. The study aims to establish a frequency-specific dose-response model using validated physiological measurements.', 'detailedDescription': 'Transcutaneous cervical vagus nerve stimulation (tcVNS) is a non-invasive neuromodulation technique capable of activating afferent vagal pathways projecting to autonomic brainstem nuclei. Although previous studies demonstrate tcVNS-related modulation of autonomic functions, the frequency-response relationship remains insufficiently explored.\n\nThis crossover trial randomizes participants to receive five stimulation conditions (sham, 10 Hz, 25 Hz, 50 Hz, 100 Hz) in counterbalanced order. HRV (Polar H10), blood pressure (Omron), and respiratory rate (Kinovea-based thoracoabdominal video tracking) are collected pre- and post-stimulation. Washout between sessions is ≥48 hours.\n\nThe study provides one of the first systematic evaluations of frequency-dependent tcVNS effects in healthy adults.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '30 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 18-30 years\n* Healthy (self-reported)\n* No cardiovascular, neurological, metabolic or psychiatric disorders\n* No regular medication affecting autonomic function\n* Non-smoker\n* BMI 18-29.9\n\nExclusion Criteria:\n\n* Pregnancy\n* Cardiac arrhythmia\n* Hypertension or hypotension\n* Chronic respiratory disorders\n* Active infection\n* Metal implants in cervical area\n* Epilepsy\n* Syncope history\n* Prior vagus stimulation experience'}, 'identificationModule': {'nctId': 'NCT07274332', 'acronym': 'AVNS-DRC', 'briefTitle': 'Frequency-Dependent Effects of Auricular Vagus Nerve Stimulation on Autonomic and Cardiovascular Parameters', 'organization': {'class': 'OTHER', 'fullName': 'Sinop University'}, 'officialTitle': 'Acute Effects of Different Frequencies of Auricular Vagus Nerve Stimulation on HRV, Blood Pressure, and Respiratory Rate: A Sham-Controlled, Randomized, Crossover Dose-Response Study', 'orgStudyIdInfo': {'id': 'tcVNS1'}, 'secondaryIdInfos': [{'id': 'IRB Number (Pending)', 'type': 'REGISTRY', 'domain': 'Gümüşhane University Clinical Research Ethics Committee'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'SHAM_COMPARATOR', 'label': '1 - Sham (0 Hz)', 'description': 'Intervention Type: Pulsetto FIT™ tcVNS Device Intervention Name: Sham tcVNS Description: Device placed on bilateral cervical region; no electrical current delivered.\n\nDose: 10 minutes', 'interventionNames': ['Device: Pulsetto FIT™ - Sham tcVNS']}, {'type': 'EXPERIMENTAL', 'label': '2 - 10 Hz tcVNS', 'description': 'Intervention Type:Pulsetto FIT™ tcVNS Device Intervention Name: tcVNS (10 Hz) Description: Bilateral cervical stimulation at 10 Hz, 250 μs pulse width. Duration: 10 minutes', 'interventionNames': ['Device: Pulsetto FIT™ - tcVNS 10 Hz']}, {'type': 'EXPERIMENTAL', 'label': '3 - tcVNS 25 Hz', 'description': 'Intervention Type:Pulsetto FIT™ tcVNS Device Intervention Name: tcVNS (25 Hz) Description: Bilateral cervical stimulation at 25 Hz, 250 μs pulse width. Duration: 10 minutes', 'interventionNames': ['Device: Pulsetto FIT™ - tcVNS 25 Hz']}, {'type': 'EXPERIMENTAL', 'label': '4 - tcVNS 50 Hz', 'description': 'Intervention Type:Pulsetto FIT™ tcVNS Device Intervention Name: tcVNS (50 Hz) Description: Bilateral cervical stimulation at 50 Hz, 250 μs pulse width. Duration: 10 minutes', 'interventionNames': ['Device: Pulsetto FIT™ - tcVNS 50 Hz']}, {'type': 'EXPERIMENTAL', 'label': '5 - tcVNS 100 Hz', 'description': 'Intervention Type:Pulsetto FIT™ tcVNS Device Intervention Name: tcVNS (100 Hz) Description: Bilateral cervical stimulation at 100 Hz, 250 μs pulse width. Duration: 10 minutes', 'interventionNames': ['Device: Pulsetto FIT™ - tcVNS 100 Hz']}], 'interventions': [{'name': 'Pulsetto FIT™ - Sham tcVNS', 'type': 'DEVICE', 'description': 'The Pulsetto FIT™ device is placed bilaterally on the cervical region (posterior margin of the sternocleidomastoid muscle).\n\nIn the sham condition, the device displays normal operational lights but delivers no electrical stimulation (0 Hz; inactive mode).\n\nThis condition is used for blinding and as the control comparator. Dose: 10 minutes', 'armGroupLabels': ['1 - Sham (0 Hz)']}, {'name': 'Pulsetto FIT™ - tcVNS 10 Hz', 'type': 'DEVICE', 'description': 'Bilateral transcutaneous cervical vagus nerve stimulation delivered via the Pulsetto FIT™ device at 10 Hz, 250 µs pulse width.\n\nCurrent intensity adjusted to a mild, non-painful tingling sensation, individualized for each participant.\n\nDose: 10 minutes', 'armGroupLabels': ['2 - 10 Hz tcVNS']}, {'name': 'Pulsetto FIT™ - tcVNS 25 Hz', 'type': 'DEVICE', 'description': 'Bilateral tcVNS using the Pulsetto FIT™ device at 25 Hz, 250 µs pulse width. Stimulation intensity set at a comfortable sensory level. Dose: 10 minutes', 'armGroupLabels': ['3 - tcVNS 25 Hz']}, {'name': 'Pulsetto FIT™ - tcVNS 50 Hz', 'type': 'DEVICE', 'description': 'Bilateral cervical vagus nerve stimulation via Pulsetto FIT™ at 50 Hz, 250 µs pulse width.\n\nIntensity adjusted to a tolerable sensory level without discomfort. Dose: 10 minutes', 'armGroupLabels': ['4 - tcVNS 50 Hz']}, {'name': 'Pulsetto FIT™ - tcVNS 100 Hz', 'type': 'DEVICE', 'description': 'Bilateral tcVNS delivered with the Pulsetto FIT™ device at 100 Hz, 250 µs pulse width.\n\nHighest stimulation frequency used in this protocol; current intensity individualized per participant comfort.\n\nDose: 10 minutes', 'armGroupLabels': ['5 - tcVNS 100 Hz']}]}, 'contactsLocationsModule': {'locations': [{'zip': '57900', 'city': 'Türkeli', 'state': 'Sinop', 'country': 'Turkey (Türkiye)', 'facility': 'Sinop University, Türkeli Vocational School (Türkeli MYO)', 'geoPoint': {'lat': 41.94764, 'lon': 34.33861}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Individual participant data will not be shared because the study includes physiological recordings (HRV, blood pressure, respiratory videos) that cannot be fully anonymized. Data sharing may pose a risk of indirect identification.\n\nOnly aggregated results will be reported in publications and presentations.\n\nIPD Sharing Time Frame:\n\nNot applicable.\n\nIPD Sharing Access Criteria:\n\nNot applicable.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'SEFA HAKTAN HATIK', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor', 'investigatorFullName': 'SEFA HAKTAN HATIK', 'investigatorAffiliation': 'Sinop University'}}}}