Vagus Nerve StimulationNCT05680337
Auricular Vagus Stimulation and Heart Rate Variability
A study testing TENS in people with Vagus Nerve Stimulation and Heart Rate Variability, run by Bakulev Scientific Center of Cardiovascular Surgery at 3 sites in Russia.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Vagus Nerve Stimulation, Heart Rate Variability
- What is being tested?
- TENS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 3 sitesRussia
- Study dates
- 1 Dec 2022to 1 Apr 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Sinus rhythm at the time of registration
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Russia3 sites
Federal Center for Cardiovascular Surgery (Astrakhan)
Astrakhan
State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital
Krasnodar
Bakulev National Medical Research Center for Cardiovascular Surgery
Moscow, 121552
About this study
Official title: Transcutaneous Electrical Auricular Vagus Stimulation and Heart Rate Variability
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.
Read the 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
- Conditions
- Vagus Nerve Stimulation, Heart Rate Variability
- Being tested
- TENS
- 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)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TENSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active TENS | Active comparator | Active 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. Receives: Device: TENS |
| Sham TENS | Sham comparator | Sham 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. Receives: Device: TENS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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 (9)
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
Measured: 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.
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
Measured: 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.
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
Measured: 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.
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
Measured: 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.
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
Measured: 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.
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
Measured: 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.
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
Measured: 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.
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
Measured: 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.
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
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2023
- Study start1 Dec 2022
- Primary completion1 Mar 2026
- Study completion1 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Vagus Nerve StimulationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 randomization of active stimulation vs. sham stimulation
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bakulev Scientific Center of Cardiovascular Surgery
- Sponsor type
- Other government
- Collaborators
- State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital, Astrakhan Federal Centre For Cardiac Surgery
- Responsible party
- Principal investigator, Vladimir A Shvartz, MD, Bakulev Scientific Center of Cardiovascular Surgery
- Investigators
- Vladimir Shvartz, Principal investigator, Bakoulev Scientific Center for Cardiovascular Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05680337
- Sponsor's protocol ID
- #6
- Status last verified
- Jul 2026
- First submitted
- 26 Dec 2022
- Last updated
- 20 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The datasets analyzed during the current study are publicly available. The data is available in the general repository "Open Science Framework" at the link
Publications
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
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
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcutaneous Electrical Auricular Vagus Stimulation and Heart Rate Variability
- ClinicalTrials.gov ID
- NCT05680337
- Acronym / sponsor ID
- #6
- 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)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Bakulev Scientific Center of Cardiovascular SurgeryOther government
- Collaborators
- State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital, Astrakhan Federal Centre For Cardiac Surgery
- Study start
- 1 Dec 2022 (actual)
- Primary completion
- 1 Mar 2026 (actual)
- Study completion
- 1 Apr 2026 (actual)
- First posted
- 11 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- 1:1 randomization of active stimulation vs. sham stimulation
| Arm | Type | Receives |
|---|---|---|
| Active TENS | Active comparator | Device: TENSActive 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 TENS | Sham comparator | Device: TENSSham 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Sinus rhythm at the time of registration
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TENSTENS 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. | Device | Active TENS, Sham TENS |
Primary outcome
Dynamics of LF/HF
Time frame: 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 /HF relative to the initial and after the end of stimulation in the groups of active and fictitious stimulation
9 secondary outcomes
HR dynamics
Time frame: 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.
Dynamics of SDNN
Time frame: 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.
Dynamics of IVB
Time frame: 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.
Dynamics of IC1
Time frame: 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.
Dynamics of IC2
Time frame: 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.
Dynamics of HF%
Time frame: 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.
Dynamics of LF%
Time frame: 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.
HF dynamics
Time frame: 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.
Dynamics of LF
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2026.
- Results publicationShvartz, 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
- Results publicationShvartz 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
- International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)Link provided by the sponsor.
- Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in NomenclatureLink provided by the sponsor.
- Does transcutaneous auricular vagus nerve stimulation affect vagally mediated heart rate variability? A living and interactive Bayesian meta-analysisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The datasets analyzed during the current study are publicly available. The data is available in the general repository "Open Science Framework" at the link
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vladimir Shvartz principal investigator
Bakoulev Scientific Center for Cardiovascular Surgery
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TENS in people with Vagus Nerve Stimulation and Heart Rate Variability, run by Bakulev Scientific Center of Cardiovascular Surgery at 3 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dynamics of LF/HF (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05680337, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026.