The Effect Of Transcutaneous Auricular Vagus Nerve Stimulation On Sports Performance And Physiological Parameters

Healthy Clinical Trial

— VNS001  

Official title:

The Effect Of Transcutaneous Auricular Vagus Nerve Stimulation On Sports Performance And Physiological Parameters In Healthy Young Individuals: Randomized, Double-Blind Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04768738
• Other study ID #: VNS001
• Status: Completed
• Phase: N/A
• Start date: February 1, 2020
• Est. completion date: November 1, 2020

Study information

• Verified date: February 2021
• Source: Sinop University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

OBJECTIVE: The aim of this study is to investigate the effect of non-invasive auricular VNS (Vagus Nerve Stimulation) on sportive performance and physiological parameters in healthy individuals. MATERIAL AND METHOD: 46 healthy young individuals aged 19.2(±1.5) years participated in the study. The participants were randomly divided into 3 groups as Above Threshold Group (n:15; 10 females, 5 males), Under Threshold Group (n:15; 10 females, 5 males) and Control Group (no stimulation) (n:16; 11 females, 5 males) according to the sensation of electrical current on ears. The participants were evaluated 3 times; before the application, after the first and second bicycle exercises. Numerical pain scale (NPS), pulse rate, blood pressure, respiratory rate, and distance travelled during exercise for sportive performance were recorded in kilometers as the evaluation method. The stimulation was done during the first bicycle exercise with 5 minutes of duration. The Kruskal-wallis, mann-whitney u test were used for the quantitative independent data obtained. In the analysis of qualitative independent data, chi-squared test was used.

Description:

This study included 46 individuals aged 18-35 years in the home patient care laboratory at Sinop University Vocational School of Turkeli. Priorities were explained and the permission of the individuals was obtained. The number of females and males was divided into 3 groups as randomized. Participants were evaluated by Numerical pain scale (NPS), pulse rate, blood pressure, respiratory rate, and saturation measurement. In addition, the distance travelled during the exercise for sportive performance was recorded in kilometers. In the study, evaluation was conducted 3 times before the application, after the first and second bicycle exercises. The study was double-blind randomized. Participants in the whole group were asked to perform bicycle exercise with maximum performance under 50 watts for 5 minutes. In all groups Vagustim device was used for stimulation. In the above threshold group, biphasic current was applied as follows; frequency 10 Hz, in Modulation mode (Modulation mode is a combination of pulse rate and pulse width modulation. The pulse rate and width are automatically varied in a cycle pattern. The pulse width is reduced by 50% from its original setting in 0.5 second, then the pulse rate is reduced by 50% from its original setting in 0.5 second. Total cycle time is 1 second.), the pulse width was 300 μs. The current intensity was kept constant where the participant felt the current comfortably and applied for 5 minutes. VNS was applied bilaterally to transmit current from the tragus and concha parts of the ear. After the first bicycle exercise, the participants were re-evaluated. In the second bicycle exercise, it was asked to perform for 5 minutes under the same load without any application. The study was evaluated for the third time and the study was completed. In the subthreshold group, the parameters were the same but the current was reduced to where the participant did not feel the current after the threshold value was reached and again applied for 5 minutes. It was re-evaluated after the first bicycle exercise. In the second bicycle exercise, he was asked to perform bicycle exercise with maximum performance for 5 minutes under the same load without any application. The study was evaluated for the third time and the study was completed. In the control group, bicycle exercise was performed under the same load with the current-free headset produced for sham applications for 5 minutes. Participants were shown that the device was working, but no current was given. It was re-evaluated after the first bicycle exercise. In the second bicycle exercise, the device was removed and asked to perform bicycle exercise with maximum performance for 5 minutes under the same load. The study was evaluated for the third time and the study was completed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: November 1, 2020
• Est. primary completion date: February 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 27 Years

Eligibility

Inclusion Criteria:

• 18-35 years age
• Being healthy

Exclusion Criteria:

• any known disease
• any drug usage

Related Conditions & MeSH terms

• Activity, Motor
• Healthy

Intervention

Device:
• Auricular Vagus Nerve Stimulation Level Of Above Threshold
Biphasic current was applied as follows; frequency 10 Hz, in Modulation mode (Modulation mode is a combination of pulse rate and pulse width modulation. The pulse rate and width are automatically varied in a cycle pattern. The pulse width is reduced by 50% from its original setting in 0.5 second, then the pulse rate is reduced by 50% from its original setting in 0.5 second. Total cycle time is 1 second.), the pulse width was 300 µs. The current intensity was kept constant where the participant felt the current comfortably and applied for 5 minutes.
• Auricular Vagus Nerve Stimulation Level Of Subthreshold
biphasic current was applied as follows; frequency 10 Hz, in Modulation mode (Modulation mode is a combination of pulse rate and pulse width modulation. The pulse rate and width are automatically varied in a cycle pattern. The pulse width is reduced by 50% from its original setting in 0.5 second, then the pulse rate is reduced by 50% from its original setting in 0.5 second. Total cycle time is 1 second.), the pulse width was 300 µs. The parameters were the same with Above Threshold Group but the current was reduced to where the participant did not feel the current after the threshold value was reached and again applied for 5 minutes.
• Auricular Vagus Nerve Stimulation Sham Method
Participants were shown that the device was working, but no current was given.

Diagnostic Test:
• 5 Minutes Bicycle Exercise
Participants in this group were asked to perform bicycle exercise with maximum performance under 50 watts for 5 minutes.

Locations

Country	Name	City	State
Turkey	Sefa Haktan Hatik	Sinop	Turkeli

Sponsors (1)

Lead Sponsor	Collaborator
Sinop University

Country where clinical trial is conducted

Turkey, 

References & Publications (28)

Annoni EM, Van Helden D, Guo Y, Levac B, Libbus I, KenKnight BH, Osborn JW, Tolkacheva EG. Chronic Low-Level Vagus Nerve Stimulation Improves Long-Term Survival in Salt-Sensitive Hypertensive Rats. Front Physiol. 2019 Jan 31;10:25. doi: 10.3389/fphys.2019.00025. eCollection 2019. — View Citation

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Antonino D, Teixeira AL, Maia-Lopes PM, Souza MC, Sabino-Carvalho JL, Murray AR, Deuchars J, Vianna LC. Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial. Brain Stimul. 2017 Sep - Oct;10(5):875-881. doi: 10.1016/j.brs.2017.05.006. Epub 2017 May 19. — View Citation

Beh SC, Friedman DI. Acute vestibular migraine treatment with noninvasive vagus nerve stimulation. Neurology. 2019 Oct 29;93(18):e1715-e1719. doi: 10.1212/WNL.0000000000008388. Epub 2019 Sep 25. — View Citation

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Chen M, Yu L, Liu Q, Jiang H, Zhou S. Vagus nerve stimulation: A spear role or a shield role in atrial fibrillation? Int J Cardiol. 2015 Nov 1;198:115-6. doi: 10.1016/j.ijcard.2015.06.171. Epub 2015 Jul 5. — View Citation

Clancy JA, Mary DA, Witte KK, Greenwood JP, Deuchars SA, Deuchars J. Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity. Brain Stimul. 2014 Nov-Dec;7(6):871-7. doi: 10.1016/j.brs.2014.07.031. Epub 2014 Jul 16. — View Citation

Colzato LS, Ritter SM, Steenbergen L. Transcutaneous vagus nerve stimulation (tVNS) enhances divergent thinking. Neuropsychologia. 2018 Mar;111:72-76. doi: 10.1016/j.neuropsychologia.2018.01.003. Epub 2018 Jan 8. — View Citation

Dalli J, Colas RA, Arnardottir H, Serhan CN. Vagal Regulation of Group 3 Innate Lymphoid Cells and the Immunoresolvent PCTR1 Controls Infection Resolution. Immunity. 2017 Jan 17;46(1):92-105. doi: 10.1016/j.immuni.2016.12.009. Epub 2017 Jan 5. — View Citation

Hong GS, Zillekens A, Schneiker B, Pantelis D, de Jonge WJ, Schaefer N, Kalff JC, Wehner S. Non-invasive transcutaneous auricular vagus nerve stimulation prevents postoperative ileus and endotoxemia in mice. Neurogastroenterol Motil. 2019 Mar;31(3):e13501. doi: 10.1111/nmo.13501. Epub 2018 Nov 8. — View Citation

Lataro RM, Silva CA, Fazan R Jr, Rossi MA, Prado CM, Godinho RO, Salgado HC. Increase in parasympathetic tone by pyridostigmine prevents ventricular dysfunction during the onset of heart failure. Am J Physiol Regul Integr Comp Physiol. 2013 Oct 15;305(8):R908-16. doi: 10.1152/ajpregu.00102.2013. Epub 2013 Aug 15. — View Citation

Lee SW, Li Q, Libbus I, Xie X, KenKnight BH, Garry MG, Tolkacheva EG. Chronic cyclic vagus nerve stimulation has beneficial electrophysiological effects on healthy hearts in the absence of autonomic imbalance. Physiol Rep. 2016 May;4(9). pii: e12786. doi: 10.14814/phy2.12786. — View Citation

Li M, Zheng C, Sato T, Kawada T, Sugimachi M, Sunagawa K. Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation. 2004 Jan 6;109(1):120-4. Epub 2003 Dec 8. — View Citation

Liu JJ, Huang N, Lu Y, Zhao M, Yu XJ, Yang Y, Yang YH, Zang WJ. Improving vagal activity ameliorates cardiac fibrosis induced by angiotensin II: in vivo and in vitro. Sci Rep. 2015 Nov 24;5:17108. doi: 10.1038/srep17108. — View Citation

Möller M, Mehnert J, Schroeder CF, May A. Noninvasive vagus nerve stimulation and the trigeminal autonomic reflex: An fMRI study. Neurology. 2020 Mar 10;94(10):e1085-e1093. doi: 10.1212/WNL.0000000000008865. Epub 2020 Feb 6. — View Citation

Nur Gökçe, E , Pinar Cengi?z, Z , Erbas, O . (2018). Uzun ömrün sirri: Vagus siniri . Istanbul Bilim Üniversitesi Florence Nightingale Tip Dergisi , 4 (3) , 154-165 . Retrieved from https://dergipark.org.tr/tr/pub/ibufntd/issue/39718/470405

Oshinsky ML, Murphy AL, Hekierski H Jr, Cooper M, Simon BJ. Noninvasive vagus nerve stimulation as treatment for trigeminal allodynia. Pain. 2014 May;155(5):1037-1042. doi: 10.1016/j.pain.2014.02.009. Epub 2014 Feb 14. — View Citation

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Sabino-Carvalho, J.L., et al., Non-invasive Vagus Nerve Stimulation Acutely Improves Blood Pressure Control in a Placebo Controlled Study. The FASEB Journal, 2017. 31(1_supplement): p. 848.8-848.8.

Silberstein SD, Calhoun AH, Lipton RB, Grosberg BM, Cady RK, Dorlas S, Simmons KA, Mullin C, Liebler EJ, Goadsby PJ, Saper JR; EVENT Study Group. Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study. Neurology. 2016 Aug 2;87(5):529-38. doi: 10.1212/WNL.0000000000002918. Epub 2016 Jul 13. — View Citation

Straube A, Ellrich J, Eren O, Blum B, Ruscheweyh R. Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS): a randomized, monocentric clinical trial. J Headache Pain. 2015;16:543. doi: 10.1186/s10194-015-0543-3. Epub 2015 Jul 9. — View Citation

Tassorelli C, Grazzi L, de Tommaso M, Pierangeli G, Martelletti P, Rainero I, Dorlas S, Geppetti P, Ambrosini A, Sarchielli P, Liebler E, Barbanti P; PRESTO Study Group. Noninvasive vagus nerve stimulation as acute therapy for migraine: The randomized PRESTO study. Neurology. 2018 Jul 24;91(4):e364-e373. doi: 10.1212/WNL.0000000000005857. Epub 2018 Jun 15. — View Citation

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Xie X, Lee SW, Johnson C, Ippolito J, KenKnight BH, Tolkacheva EG. Intermittent vagal nerve stimulation alters the electrophysiological properties of atrium in the myocardial infarction rat model. Annu Int Conf IEEE Eng Med Biol Soc. 2014;2014:1575-8. doi: 10.1109/EMBC.2014.6943904. — View Citation

Yoo PB, Liu H, Hincapie JG, Ruble SB, Hamann JJ, Grill WM. Modulation of heart rate by temporally patterned vagus nerve stimulation in the anesthetized dog. Physiol Rep. 2016 Feb;4(2). pii: e12689. doi: 10.14814/phy2.12689. — View Citation

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* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sportive performance	Athletic performance during exercise in healthy individuals, cycling length in kilometers. Measured twice, during first and second exercises.	Change from Baseline at Second Exercise
Secondary	Pulse	Heart beats per minute. Measured 3 times; before the first exercise, after the first exercise, after the second exercise.	Change from Baseline at 5 minutes
Secondary	Pulse	Heart beats per minute. Measured 3 times; before the first exercise, after the first exercise, after the second exercise.	15 minutes
Secondary	Numerical pain scale (NPS),	Amount of pain described by patients. Patients are asked to circle the number between 0 and 10. Zero represents 'no pain at all' whereas ten represents 'the worst pain ever possible'. Measurement is done twice; after the first and the second bicycle exercises.	Change from Baseline at 15 minutes
Secondary	Respiratory Rate	The respiratory rate corresponds to the number of breaths taken per minute. The rate of respiration measured 3 times; before the first exercise, after the first exercise, after the second exercise.	Change from Baseline at 5 minutes
Secondary	Respiratory Rate	The respiratory rate corresponds to the number of breaths taken per minute. The rate of respiration measured 3 times; before the first exercise, after the first exercise, after the second exercise.	15 minutes
Secondary	Systolic Blood Pressure	Systolic Pressure measured 3 times; before the first exercise, after the first exercise, after the second exercise. Blood pressure recorded as mmHg. Measured 3 times; before the first exercise, after the first exercise, after the second exercise.	Change from Baseline at 5 minutes
Secondary	Systolic Blood Pressure	Systolic Pressure measured 3 times; before the first exercise, after the first exercise, after the second exercise. Blood pressure recorded as mmHg. Measured 3 times; before the first exercise, after the first exercise, after the second exercise.	15 minutes
Secondary	Diastolic Blood Pressure	Diastolic Pressure measured 3 times; before the first exercise, after the first exercise, after the second exercise. Blood pressure recorded as mmHg. Measured 3 times; before the first exercise, after the first exercise, after the second exercise.	Change from Baseline at 5 minutes
Secondary	Diastolic Blood Pressure	Diastolic Pressure measured 3 times; before the first exercise, after the first exercise, after the second exercise. Blood pressure recorded as mmHg. Measured 3 times; before the first exercise, after the first exercise, after the second exercise.	15 minutes
Secondary	Saturation	Percentage of Oxygen saturation in blood. Measured 3 times; before the first exercise, after the first exercise, after the second exercise.	Change from Baseline at 5 minutes
Secondary	Saturation	Percentage of Oxygen saturation in blood. Measured 3 times; before the first exercise, after the first exercise, after the second exercise.	15 minutes