Influence of Manual and Electrical Vagal Stimulation on Autonomic Activity and Other Dysautonomous Symptoms in a Healthy Population.

NCT07660744 | Not Yet Recruiting

• 1 other identifier: NV0001
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of this clinical, longitudinal, prospective, randomised (randomised) unmasked study is to analyse whether electrical and manual vagal stimulation produces changes in heart rate variability in a healthy population and it have a beneficial clinical effect in reducing dysautonomic symptoms. The main questions it seeks to answer are:

• Will non-invasive (manual and electrical) stimulation of the vagus nerve produce a significant change in heart rate variability, generating effects on the regulation of the autonomic nervous system, increasing the activation of the parasympathetic nervous system and decreasing the activation of the sympathetic nervous system?
• Will non-invasive (manual and electrical) stimulation of the vagus nerve have a beneficial clinical effect in reducing dysautonomic symptoms such as fatigue and improving sleep quality?
• Will noninvasive (manual and electrical) vagus nerve stimulation improve quality of life?
• Are there differences in the level of satisfaction with the treatment after the intervention program received? Two groups of participants will be formed:
• Transcutaneous auricular vagus nerve stimulation consists of applying electrical stimulation to the auricular branch of the vagus nerve using a 2-pole stimulation electrode. Stimulation is performed for 1 hour per day for 10 days (5 days per week).
• Manual vagus nerve intervention consists of applying a protocol of manual therapy techniques to the vagus nerve and along its path, during 4 sessions lasting 30 minutes, 2 interventions per week.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Heart rate variability

  Heart rate variability (HRV) analysis is proposed as a non-invasive and reliable measure to indirectly assess autonomic nervous system dysfunction. Two HRV parameters/domains are assessed: frequency and time. Frequency parameters: the high-frequency (HF) measurement is an indicator of parasympathetic nervous system activity, the low-frequency (LF) measurement is an indicator of sympathetic nervous system activity and finally the relationship between both parameters LH/HF indicates the balance between both systems. Time parameters: a significant decrease in the Standard deviation of the normal-to-normal interval and the Root mean square successive difference and pNN50 indicators would indicate a decrease in parasympathetic nervous system activity. A Polar® H10 chest strap connected to a mobile phone will be used to collect HRV data and the data will be analyzed with Elite software.

  From the beginning of the treatment until its completion in 2 weeks

Secondary Outcomes (4)

• Questions about the quality of the sleep: Pittsburgh Sleep Quality Index. (PSQI)

  From the start of treatment until its completion at 2 weeks.

• Quality of life: Eqol5 Questionnaire

  From the start of treatment until its completion at 2 weeks.

• Fatigue: FACIT Fatigue Scale

  From the start of treatment until its completion at 2 weeks.

• Degree of satisfaction regarding the treatment: Treatment Satisfaction Scale (CRES-4)

  From the start of treatment until its completion at 2 weeks.

Study Arms (2)

Vagus nerve electrical stimulation group

EXPERIMENTAL

The intervention consists of applying electrical transcutaneous stimulation to the auricular branch of the vagus nerve with a 2-pole stimulation electrode. A commercial transcutaneous electrical stimulation device approved for use in humans (tVNS R (Hook), from tVNS® Technologies GmbH, Erlangen (Germany)) will be used. Electrode will be placed on the left ear in contact with the cymba conchae, an area innervated by the auricular branch of the left vagus nerve. Stimulation protocol: Stimulation will be administered in cycles of 60 minutes/day for 10 days (5 days a week). The stimulation parameters are: Pulse width: 500 μs, Frequency: 25 Hz, Alternating duty cycle: 60 seconds ON followed by 10 seconds OFF, Total time: 60 minutes per day. Current intensity: 200% of the perception threshold, provided it is tolerated and does not cause pain.

Device: Electrical stimulation of the vagus nerve

Vagus nerve manual stimulation group

EXPERIMENTAL

The intervention consists of applying a protocol of manual therapy techniques to the vagus nerve and along its path, during 4 sessions of 30 minutes each, 2 interventions per week for 2 consecutive weeks. The therapeutic protocol is structured around a total of nine specific manoeuvres. The intervention will begin with the application of three techniques targeting the cervical region, followed by two manoeuvres focusing on the anterior region of the neck. This will be followed by two techniques performed on the thorax and, finally, two mobilisations targeting the abdominal region. The protocol will be based on previously published studies: Bayo-Tallón V and Giles PD.

Procedure: Manual stimulation of vagus nerve

Interventions

Electrical stimulation of the vagus nerve DEVICE

The intervention consists of applying transcutaneous electrical stimulation to the auricular branch of the vagus nerve using a bipolar stimulation electrode. A commercially available transcutaneous electrical stimulation device approved for human use will be used (tVNS R (Hook), from tVNS® Technologies GmbH, Erlangen, Germany). The electrode will be placed on the left ear in contact with the cimba turbinate, an area innervated by the auricular branch of the left vagus nerve. Stimulation protocol: Stimulation will be administered in 60-minute/day cycles for 10 days (5 days a week). Stimulation parameters are: Pulse width: 500 μs, Frequency: 25 Hz, Alternating duty cycle: 60 seconds ON followed by 10 seconds OFF, Total time: 60 minutes per day. Current intensity: 200% of the perception threshold, as long as it is tolerated and does not cause pain.

Vagus nerve electrical stimulation group

Manual stimulation of vagus nerve PROCEDURE

The intervention consists of applying a protocol of manual therapy techniques to the vagus nerve and its pathway, during four 30-minute sessions, two interventions per week for two consecutive weeks. The therapeutic protocol is structured around a total of nine specific maneuvers. The intervention will begin with the application of three techniques targeting the cervical region, followed by two maneuvers focused on the anterior region of the neck. Two techniques will then be performed on the thorax, and finally, two mobilizations targeting the abdominal region.

Vagus nerve manual stimulation group

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteers between 40 and 70 years of age.
• No known neurological pathology.
• Willingness to participate voluntarily in the study.

You may not qualify if:

• Cognitive impairment objectively assessed by a neurologist and considered relevant.
• Contraindications for the application of transcutaneous auricular stimulation (implanted cardiac pacemaker or deep brain stimulation treatment).
• Consumption of tea, caffeine, energy drinks, alcohol or tobacco in the two hours prior to the intervention.

Sponsors & Collaborators

• Escoles Universitaries Gimbernat: lead

Related Publications (14)

• Schaffarczyk M, Rogers B, Reer R, Gronwald T. Validity of the Polar H10 Sensor for Heart Rate Variability Analysis during Resting State and Incremental Exercise in Recreational Men and Women. Sensors (Basel). 2022 Aug 30;22(17):6536. doi: 10.3390/s22176536.

  PMID: 36081005 BACKGROUND

• Perez-Alcalde AI, Galan-Del-Rio F, Fernandez-Rodriguez FJ, de la Plaza San Frutos M, Garcia-Arrabe M, Gimenez MJ, Ruiz-Ruiz B. The Effects of a Single Vagus Nerve's Neurodynamics on Heart Rate Variability in Chronic Stress: A Randomized Controlled Trial. Sensors (Basel). 2024 Oct 26;24(21):6874. doi: 10.3390/s24216874.

  PMID: 39517768 BACKGROUND

• Miyagi T, Yamazato M, Nakamura T, Tokashiki T, Namihira Y, Kokuba K, Ishihara S, Sakima H, Ohya Y. Power spectral analysis of heart rate variability is useful as a screening tool for detecting sympathetic and parasympathetic nervous dysfunctions in Parkinson's disease. BMC Neurol. 2022 Sep 10;22(1):339. doi: 10.1186/s12883-022-02872-2.

  PMID: 36088296 BACKGROUND

• Carta G, Seregni A, Casamassima A, Galli M, Geuna S, Pagliaro P, Zago M. Validation and Reliability of a Novel Vagus Nerve Neurodynamic Test and Its Effects on Heart Rate in Healthy Subjects: Little Differences Between Sexes. Front Neurosci. 2021 Sep 6;15:698470. doi: 10.3389/fnins.2021.698470. eCollection 2021.

  PMID: 34552462 BACKGROUND

• Tutusaus R, Potau JM. Sistema fascial. Anatomía, valoración y tratamiento. Madrid: Editorial Panamericana Médica; 2015.

  BACKGROUND

• Pilat A. Terapias Miofasciales: Inducción Miofascial. Madrid: McGraw-Hill Interamericana de España S.L.; 2003.

  BACKGROUND

• Milnes K, Moran RW. Physiological effects of a CV4 cranial osteopathic technique on autonomic nervous system function: A preliminary investigation. International Journal of Osteopathic Medicine. 2007 Volume 10, Issue 1: 8-17. doi: 10.1016/j.ijosm.2007.01.003.ISSN 1746-0689.

  BACKGROUND

• Arienti C, Farinola F, Ratti S, Dacco S, Fasulo L. Variations of HRV and skin conductance reveal the influence of CV4 and Rib Raising techniques on autonomic balance: A randomized controlled clinical trial. J Bodyw Mov Ther. 2020 Oct;24(4):395-401. doi: 10.1016/j.jbmt.2020.07.002. Epub 2020 Jul 31.

  PMID: 33218540 BACKGROUND

• Lench DH, Turner TH, McLeod C, Boger HA, Lovera L, Heidelberg L, Elm J, Phan A, Badran BW, Hinson VK. Multi-session transcutaneous auricular vagus nerve stimulation for Parkinson's disease: evaluating feasibility, safety, and preliminary efficacy. Front Neurol. 2023 Jul 18;14:1210103. doi: 10.3389/fneur.2023.1210103. eCollection 2023.

  PMID: 37554394 BACKGROUND

• Sigurdsson HP, Hunter H, Alcock L, Wilson R, Pienaar I, Want E, Baker MR, Taylor JP, Rochester L, Yarnall AJ. Safety and tolerability of adjunct non-invasive vagus nerve stimulation in people with parkinson's: a study protocol. BMC Neurol. 2023 Feb 3;23(1):58. doi: 10.1186/s12883-023-03081-1.

  PMID: 36737716 BACKGROUND

• Giles PD, Hensel KL, Pacchia CF, Smith ML. Suboccipital decompression enhances heart rate variability indices of cardiac control in healthy subjects. J Altern Complement Med. 2013 Feb;19(2):92-6. doi: 10.1089/acm.2011.0031. Epub 2012 Sep 20.

  PMID: 22994907 BACKGROUND

• Bayo-Tallon V, Esquirol-Caussa J, Pamias-Massana M, Planells-Keller K, Palao-Vidal DJ. Effects of manual cranial therapy on heart rate variability in children without associated disorders: Translation to clinical practice. Complement Ther Clin Pract. 2019 Aug;36:125-141. doi: 10.1016/j.ctcp.2019.06.008. Epub 2019 Jul 2.

  PMID: 31383430 BACKGROUND

• Redgrave J, Day D, Leung H, Laud PJ, Ali A, Lindert R, Majid A. Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Brain Stimul. 2018 Nov-Dec;11(6):1225-1238. doi: 10.1016/j.brs.2018.08.010. Epub 2018 Aug 23.

  PMID: 30217648 BACKGROUND

• Wang Y, Zhan G, Cai Z, Jiao B, Zhao Y, Li S, Luo A. Vagus nerve stimulation in brain diseases: Therapeutic applications and biological mechanisms. Neurosci Biobehav Rev. 2021 Aug;127:37-53. doi: 10.1016/j.neubiorev.2021.04.018. Epub 2021 Apr 21.

  PMID: 33894241 BACKGROUND

Central Study Contacts

Jorge Esquirol Caussa

CONTACT

610083409; jordi.esquirol@eug.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Physiotherapy and PhD student

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: June 22, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: October 2025 - July 2026