Auricular Vagus Stimulation and Heart Rate Variability

Heart Rate Variability Clinical Trial

Official title:

Transcutaneous Electrical Auricular Vagus Stimulation and Heart Rate Variability

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05680337
• Other study ID #: #6
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2022
• Est. completion date: July 1, 2025

Study information

• Verified date: June 2024
• Source: Bakulev Scientific Center of Cardiovascular Surgery
• Contact: Vladimir Shvartz
• Phone: +79032619292
• Email: vashvarts[@]bakulev.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Transcutaneous electrical stimulation of the auricular vagus nerve (TENS) is a promising method of neuromodulation of the autonomic nervous system in patients with various pathologies. The use of this method requires the determination of a reliable biomarker of successful activation of the vagus nerve using TENS. Currently, most studies focus on the assessment of heart rate variability (HRV) as a marker of the functioning of the autonomic nervous system.

Despite the physiological justification of HRV as a biomarker for TENS, the data on the effects of TENS on HRV are ambiguous. In some studies, a significant decrease in the ratio of spectral characteristics (LF/HF) in active TENS was found in comparison with fictitious stimulation (sham), which indicated an increase in the parasympathetic component of HRV. However, other studies have not revealed an increase in HRV.

Description:

Transcutaneous vagus nerve stimulation (TENS) involves the stimulation of the left and/or right auricular branch of the vagus nerve in the area of the cymba concha with low-frequency electrical impulses. The auricular branch of the vagus nerve runs superficially, which makes it a favorable target for non-invasive stimulation techniques to modulate vagal activity. It gained popularity due to minimal side effects and low cost.

This method is a new, cost-effective alternative to invasive cervical vagus nerve stimulation (iVNs), which is an FDA-approved treatment of depression resistant to the treatment, epilepsy and other pathologies.

The use of TENS has shown similar positive results as iVNs, for example, in reducing symptoms in patients with depression and changing the early visual processing of negative emotional stimuli in adolescent depression. Similarly, positive effects of TENS have also been found in chronic pain and epilepsy. These similarities in effects can be explained by the similarity of brain network activation achieved by iVNs and TENS.

The lack of similarity between behavioral studies and numerous theories of physiological processes in TENS make it necessary to determine a reliable biomarker of successful activation of the vagus nerve using TENS. Although many potential biomarkers have been proposed, most studies have focused on HRV.

Despite the physiological justification of HRV as a biomarker for TENS, the data on the effects of TENS on HRV are ambiguous. In some studies, a significant decrease in the ratio of spectral characteristics (LF/HF) in active TENS compared to fictitious stimulation (sham) was found, indicating an increase in the parasympathetic component of HRV.

However, other studies have not revealed an increase in HRV. Large methodological differences between studies, such as different stimulation devices, sides and places of stimulation, experimental schemes, reported HRV parameters and stimulation protocols, reduce comparability between studies.

One of the most striking examples is the use of various control conditions. While in most studies active TENS are compared with imitation of the earlobe as an independent variable, as recommended, in some studies active stimulation of the tragus was compared with a control state without stimulation or with a fictitious state without stimulation when the electrode is placed on the ear, but no electric current is applied.

The development of international agreed consensus guidelines on TENS research reporting should address these issues. Although TENS represents a potential treatment option for many disorders and it is an interesting tool for experimental research, it needs to be studied in an objective and reliable way before its true place as a neuro-immunomodulatory intervention can be determined.

The investigators plan to conduct a study on the assessment of TENS on the dynamics of HRV parameters with reporting according to the international consensus document https://www.frontiersin.org/articles/10.3389/fnhum.2020.568051/full#B235

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: July 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Sinus rhythm at the time of registration

Exclusion Criteria:

• Frequent ventricular / supraventricular extrasystole, 2d/3d degree AV Block

• Taking glucocorticosteroids in the last 1 month

• Taking any antiarrhythmics, except beta blockers

• Severe chronic renal or liver pathology

Related Conditions & MeSH terms

• Heart Rate Variability
• Vagus Nerve Stimulation

Intervention

Device:
• TENS
TENS stimulation will occur within 10 minutes. HRV parameters will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.

Locations

Country	Name	City	State
Russian Federation	Federal Center for Cardiovascular Surgery (Astrakhan)	Astrakhan
Russian Federation	State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital	Krasnodar
Russian Federation	Bakulev National Medical Research Center for Cardiovascular Surgery	Moscow

Sponsors (3)

Lead Sponsor	Collaborator
Bakulev Scientific Center of Cardiovascular Surgery	Astrakhan Federal Centre For Cardiac Surgery, State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital

Country where clinical trial is conducted

Russian Federation, 

References & Publications (2)

Shvartz V.A., Sizhazhev E.M. Percutaneous stimulation of the auricular branch of the vagus: the potential of the method of treatment of different cardiovascular diseases. Clinical Physiology of Circulation. 2023; 20 (1): 5-15 (in Russ.). DOI: 10.24022/181

Shvartz, V.; Sizhazhev, E.; Sokolskaya, M.; Koroleva, S.; Enginoev, S.; Kruchinova, S.; Shvartz, E.; Golukhova, E. The Effect of Short-Term Transcutaneous Electrical Stimulation of Auricular Vagus Nerve on Parameters of Heart Rate Variability. Data 2023,

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dynamics of LF/HF	Changes in the level of LF /HF relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation	This parameter will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.
Secondary	HR dynamics	Changes in the HR level relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation	This parameter will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.
Secondary	Dynamics of SDNN	Changes in the level of SDNN relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation	This parameter will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.
Secondary	Dynamics of IVB	Changes in the level of IVB relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation	This parameter will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.
Secondary	Dynamics of IC1	Changes in the level of IC1 relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation. IC1 (Index Centralization) = (HF+LF)/VLF	This parameter will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.
Secondary	Dynamics of IC2	Changes in the level of IC2 relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation. IC2 (Index Centralization) = (VHF+LF)/LF	This parameter will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.
Secondary	Dynamics of HF%	Changes in the level of HF% relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation	This parameter will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.
Secondary	Dynamics of LF%	Changes in the level of LF% relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation	This parameter will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.
Secondary	HF dynamics	Changes in the HF level relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation	This parameter will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.
Secondary	Dynamics of LF	Changes in the level of LF relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation	This parameter will be evaluated before stimulation initially at rest, in the first 5 minutes of stimulation, in the second 5 minutes of stimulation and after the end of stimulation.

External Links

•   Does transcutaneous auricular vagus nerve stimulation affect vagally mediated heart rate variability? A living and interactive Bayesian meta-analysis
•   International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)
•   Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature