Effect of Recording Duration on Heart Rate Variability During taVNS

Official title

Effect of Recording Duration on Heart Rate Variability During Transcutaneous Auricular Vagus Nerve Stimulation: A Randomized, Sham-Controlled Crossover Study

Overview

This study aims to evaluate how different heart rate variability (HRV) recording durations reflect autonomic nervous system responses during transcutaneous auricular vagus nerve stimulation (taVNS) in healthy adults. In a randomized, sham-controlled crossover design, participants will attend two separate sessions and receive both active taVNS and sham stimulation in randomized order. During each session, a continuous 10-minute HRV recording will be obtained, and 1-minute, 5-minute, and 10-minute analysis windows will be compared. Blood pressure and pulse will also be measured before and after stimulation. The study will investigate whether shorter or longer HRV recording durations provide results comparable to the standard 5-minute recording and which duration most reliably detects autonomic changes during taVNS.

Detailed description

The vagus nerve plays a central role in autonomic regulation, and heart rate variability (HRV) is a widely used noninvasive marker of autonomic nervous system activity. Transcutaneous auricular vagus nerve stimulation (taVNS) has increasingly been used in experimental and clinical research as a noninvasive method to modulate vagal activity. Although previous studies suggest that taVNS may influence parasympathetic activity, HRV measurement duration remains an important methodological issue. Standard short-term HRV analysis is commonly based on 5-minute recordings, but ultra-short and longer recordings are also used, and their validity during taVNS has not been sufficiently clarified.

This study is designed to determine whether different HRV recording durations provide comparable and reliable information during taVNS. The study will use a randomized, sham-controlled crossover design. Healthy adult participants will attend two sessions separated by a washout period of 48 to 72 hours. In one session, participants will receive active taVNS; in the other, they will receive sham stimulation. The order of sessions will be randomized.

During each session, HRV data will be collected continuously for 10 minutes using a Polar H10 chest strap. From this single uninterrupted recording, 1-minute, 5-minute, and 10-minute analysis windows will be derived. HRV parameters from time-domain and frequency-domain analyses will be calculated. Blood pressure and pulse will be measured before and after the intervention using an automated upper-arm blood pressure monitor.

Active taVNS will be applied to the cymba conchae region of the ear using commonly reported stimulation parameters. Sham stimulation will be delivered with the same device and similar sensory conditions, but at a non-vagal ear location to minimize physiologic vagal effects. This design is intended to control for nonspecific sensory and expectation-related effects.

The primary objective is to assess whether the standard 5-minute HRV recording during taVNS detects autonomic effects compared with sham stimulation. Secondary objectives are to examine the agreement between 1-minute, 5-minute, and 10-minute HRV measurements and to evaluate whether shorter or longer recordings provide additional methodological value. The relationship between HRV findings and hemodynamic responses, including blood pressure and pulse, will also be explored. This study may help identify the most appropriate HRV recording duration for future taVNS research and contribute to methodological standardization in this field.

Interventions

• Device Transcutaneous Auricular Vagus Nerve Stimulation
  Active transcutaneous auricular vagus nerve stimulation will be applied bilaterally to the cymba conchae region of the ear using a transcutaneous stimulation device. Stimulation will be delivered for 10 minutes with a frequency of 25 Hz, a pulse width of 200 to 300 microseconds, and an individually adjusted intensity that is clearly perceptible but not painful. Heart rate variability will be recorded continuously during the intervention.
• Device Sham Stimulation
  Sham stimulation will be delivered for 10 minutes using the same transcutaneous stimulation device and similar stimulation settings as the active intervention, but the stimulation will be applied to a non-vagal ear region, such as the earlobe or helix, to minimize physiologic vagal effects while maintaining similar sensory input. Heart rate variability will be recorded continuously during the intervention.

Primary outcome measures

• Difference in 5-minute lnRMSSD During Active taVNS Compared With Sham Stimulation [Time frame: During the 10-minute intervention period at each study session]

Secondary outcome measures (5)

• Agreement Between 1-minute and 5-minute HRV Measurements During Active taVNS [Time frame: During the 10-minute intervention period at each active taVNS session]
• Comparison of 10-minute and 5-minute HRV Measurements During Active taVNS [Time frame: During the 10-minute intervention period at each active taVNS session]
• Effect of Recording Duration on HRV Differences Between Active taVNS and Sham Stimulation [Time frame: During the 10-minute intervention period at each study session]
• Change in Systolic and Diastolic Blood Pressure After Active taVNS Compared With Sham Stimulation [Time frame: Immediately before and immediately after each 10-minute intervention session]
• Change in Pulse Rate After Active taVNS Compared With Sham Stimulation [Time frame: Immediately before and immediately after each 10-minute intervention session]

Eligibility criteria

Inclusion criteria

• Healthy volunteers aged 18 to 40 years
• Able and willing to provide informed consent
• Able to tolerate active transcutaneous auricular vagus nerve stimulation and sham stimulation
• Able to comply with study instructions, including restrictions related to caffeine, nicotine, and heavy exercise before assessment
• No condition preventing heart rate variability, blood pressure, or pulse measurements

Exclusion criteria

• Diagnosed cardiovascular disease, arrhythmia, or pacemaker use
• History of neurologic disease that may affect autonomic nervous system function
• Regular use of medications that may affect heart rate variability or autonomic responses, including beta blockers, antiarrhythmics, or anticholinergic drugs
• Active ear infection, dermatologic lesion, or any ear condition that may interfere with stimulation
• Marked pain, discomfort, or intolerance during stimulation
• Acute infection, fever, or other acute health problem on the measurement day
• Heart rate variability data that cannot be evaluated because of excessive motion artifact

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Basic science

Study locations

Turkey (Türkiye) · 1 center

• Artvin Coruh University, Artvin Vocational School, Disabled Care and Rehabilitation Labora — Artvin

Publications

• Frangos E, Ellrich J, Komisaruk BR. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul. 2015 May-Jun;8(3):624-36. doi: 10.1016/j.brs.2014.11.018. Epub 2014 Dec 6. PMID 25573069
• Shaffer F, Ginsberg JP. An Overview of Heart Rate Variability Metrics and Norms. Front Public Health. 2017 Sep 28;5:258. doi: 10.3389/fpubh.2017.00258. eCollection 2017. PMID 29034226
• 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. PMID 25164906
• Peuker ET, Filler TJ. The nerve supply of the human auricle. Clin Anat. 2002 Jan;15(1):35-7. doi: 10.1002/ca.1089. PMID 11835542

Identifiers

NCT: NCT07526415 · TAVNS6

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗