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Auricular Vagus Stimulation and Heart Rate Variability

Not Applicable
Recruiting
Conditions
Vagus Nerve Stimulation
Heart Rate Variability
Interventions
Device: TENS
Registration Number
NCT05680337
Lead Sponsor
Bakulev Scientific Center of Cardiovascular Surgery
Brief 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.

Detailed 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 & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
600
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Active TENSTENSActive will be performed with using a TENS device with an ear clip attached to the tragus of the left ear (which is innervated by auricular branch of the vagus nerve) at 20 Hz, 200 μs at a current just below discomfort threshold.
Sham TENSTENSSham will be performed with using a TENS device with an ear clip attached to the left earlobe (which is devoid of vegas innervation) at 20 Hz, 200 μs at a current just below discomfort threshold.
Primary Outcome Measures
NameTimeMethod
Dynamics of LF/HFThis 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.

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

Secondary Outcome Measures
NameTimeMethod
Dynamics of IC1This 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.

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

Dynamics of HF%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.

Changes in the level of HF% relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation

Dynamics of 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.

Changes in the level of LF% relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation

HF dynamicsThis 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.

Changes in the HF level relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation

Dynamics of LFThis 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.

Changes in the level of LF relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation

HR dynamicsThis 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.

Changes in the HR level relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation

Dynamics of SDNNThis 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.

Changes in the level of SDNN relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation

Dynamics of IVBThis 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.

Changes in the level of IVB relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation

Dynamics of IC2This 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.

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

Trial Locations

Locations (3)

Bakulev National Medical Research Center for Cardiovascular Surgery

🇷🇺

Moscow, 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

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