Clinical trial NCT05680337: Auricular Vagus Stimulation and Heart Rate Variability
Official title: Transcutaneous Electrical Auricular Vagus Stimulation and Heart Rate Variability
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Vagus Nerve Stimulation
Heart Rate Variability
Keywords: auricular stimulation
auricular vagus nerve stimulation
heart rate
transcutaneous vagus nerve stimulation (TENS)
vagus nerve stimulation (VNS)
heart rate variability
power of high-frequency oscillations (HF)
power of low-frequency oscillations (LF)
power of very low frequency oscillations (VLF)
power of ultra-low frequency oscillations (ULF)
LF/HF
index centralization (IC)
index of vegetative balance (IVB)
Lead sponsor: Bakulev Scientific Center of Cardiovascular Surgery
Sponsor class: OTHER_GOV
Collaborators: name: State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital
name: Astrakhan Federal Centre For Cardiac Surgery
First posted: 2023-01-11
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization of active stimulation vs. sham stimulation
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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

Primary outcomes:
measure: Dynamics of LF/HF
timeFrame: 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 outcomes:
measure: HR dynamics
timeFrame: 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.
measure: Dynamics of SDNN
timeFrame: 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.
measure: Dynamics of IVB
timeFrame: 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.
measure: Dynamics of IC1
timeFrame: 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.
measure: Dynamics of IC2
timeFrame: 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.
measure: Dynamics of HF%
timeFrame: 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.
measure: Dynamics of LF%
timeFrame: 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.
measure: HF dynamics
timeFrame: 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.
measure: Dynamics of LF
timeFrame: 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.
Other outcomes:
Locations:
city: Astrakhan
country: Russian Federation
facility: Federal Center for Cardiovascular Surgery (Astrakhan)
city: Krasnodar
country: Russian Federation
facility: State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Bakulev National Medical Research Center for Cardiovascular Surgery
Study officials:
affiliation: Bakoulev Scientific Center for Cardiovascular Surgery
name: Vladimir Shvartz
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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, 8, 87. https://doi.org/10.3390/data8050087
citation: 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: 10.24022/1814-6910-2023-20-1-5-15