Effects of Left and Bilateral Transcutaneous Auricular Vagus Nerve Stimulation on Pain, Mood, and Autonomic Function in Female Fibromyalgia Patients

NCT06871306 | Completed

• 1 other identifier: 12.08.2021/31
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study aimed to examine the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on pain, depression, anxiety, functionality, and autonomic function in fibromyalgia syndrome (FMS). primary hypothesis: TAVSS application is not an effective treatment for depression, physical limitation, functional disability, anxiety, pain and autonomic nerve system in female FMS patients. secondary hypothesis: TAVSS application is an effective treatment for depression, physical limitation, functional disability, anxiety, pain and autonomic nerve system in female FMS patients.

Conditions

Fibromyalgia Syndrome

Outcome Measures

Primary Outcomes (5)

• Fibromyalgia Impact Questionnaire

  Fibromyalgia Impact Questionnaire is a scale consisting of 10 questions, displaying physical function, absence from work, feeling well, fatigue, difficulty at work, pain, stillness, morning fatigue, anxiety, and depression. Apart from feeling well, low scores indicate recovery or being slightly affected by the disease. The maximum score of each subheading is 10 and the total score is 100. FIQ score was evaluated as being slightly affected under 50 points, moderately affected between 50-69, and heavily affected at 70 and more.

  From enrollment to the 28th day of control

• Visual Analog Scale

  Pain severity was assessed with the Visual Analog Scale (VAS), which is scored between 0 and 10, and is used to evaluate pain. 0 denotes no pain and 10 denotes unbearably severe pain. Participants were asked to mark the pain they felt on a 10 cm straight line and the value found was recorded in cm.

  From enrollment to the 28th day of control

• PNS Index Activity

  The PNS Index was used to measure ANS activity, indicating the evaluation of a person's parasympathetic nervous system activity compared to normal resting values. (https://www.kubios.com/publications/) The PNS index serves as a quantitative indicator of ANS function by reflecting the activity levels of its branches. This measures play a crucial role in heart rate variability (HRV) analysis, offering valuable insights into an individual's stress levels and recovery capacity. For PNS activity reduces heart rate and enhances HRV. HRV changes in pathological conditions (ischemic heart disease etc.), and decreased variability is a predictor of worse outcomes. Cyclical fluctuations in heart rate reveal changes in the ANS. The e-motion Faros device has been classified as a Class II medical device by Health Canada. After recording the R-R intervals of heart rate by e-motion Faros, the data were transferred to Kubios software for interpretation of HRV.

  From enrollment to the 28th day of control

• SNS Index Activity

  The SNS Index was used to measure ANS activity, indicating the evaluation of a person's sympathetic nervous system activity compared to normal resting values. (https://www.kubios.com/publications/) The SNS index serves as a quantitative indicator of ANS function by reflecting the activity levels of its branches. This measures play a crucial role in heart rate variability (HRV) analysis, offering valuable insights into an individual's stress levels and recovery capacity. A heightened SNS index is often associated with increased sympathetic activity, commonly linked HRV changes in pathological conditions (ischemic heart disease etc.), and decreased variability is a predictor of worse outcomes. Cyclical fluctuations in heart rate reveal changes in the ANS. The e-motion Faros device has been classified as a Class II medical device by Health Canada. After recording the R-R intervals of heart rate by e-motion Faros, the data were transferred to Kubios software for interpretation of HRV.

  From enrollment to the 28th day of control

• Assessment of Autonomic Nervous System Activity (SNS and PNS Index)

  Autonomic nervous system (ANS) activity, including both sympathetic (SNS) and parasympathetic (PNS) indices, is assessed using the eMotion Faros device. The device continuously records electrocardiographic (ECG) signals via a single-lead chest electrode setup. It is classified as a Class II medical device by Health Canada. The collected ECG data are analyzed using proprietary Kubios HRV Premium software, which computes time-domain, frequency-domain, and nonlinear heart rate variability (HRV) parameters. SNS and PNS indices are derived using Kubios' built-in algorithms that combine spectral analysis (e.g., LF/HF ratio), stress index, and other HRV-derived metrics to estimate autonomic balance. Higher SNS index values indicate increased sympathetic activity, while higher PNS index values reflect enhanced parasympathetic tone.

  From enrollment to the 28th day of control

Secondary Outcomes (2)

• Beck Depression Index

  From enrollment to the 28th day of control

• Beck Anxiety Inventory

  From enrollment to the 28th day of control

Study Arms (2)

Left taVNS

ACTIVE COMPARATOR

Left taVNS group received taVNS stimulation through the left ear for 11 sessions.

Device: Transcutaneous Auricular Vagus Nerve Stimulation

Bilateral taVNS

ACTIVE COMPARATOR

Bilateral taVNS group received taVNS stimulation through the bilateral ears for 11 sessions.

Device: Transcutaneous Auricular Vagus Nerve Stimulation

Interventions

Transcutaneous Auricular Vagus Nerve Stimulation DEVICE

taVNS was performed using the Vagustim device (Vagustim Health Technologies, Teknokent, Istanbul, Türkiye) at the tragus and concha regions for 30 minutes, with a frequency of 25 Hz and a pulse width of 300 µs in both groups. The difference in stimulation between the groups depends only on to which ear it was applied. Electrical stimulation was increased in 0.1 mA steps until the detection threshold was reached.

Bilateral taVNS; Left taVNS

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Only female participants are eligible for this study, as fibromyalgia syndrome is more prevalent in the female population.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female volunteer participants
• Aged 18-45 with regular menstrual cycles
• Diagnosed with FMS (Widespread Pain Index≥ 17
• Symptom Severity Scale≥ 21) according to the 2013 ACR diagnostic criteria by a specialist physician.

You may not qualify if:

• Neurological deficits,
• Diabetes
• Neuropathic disorders
• Chronic inflammation
• Immune deficiencies
• Cardiac diseases
• Pregnancy
• Being in the perimenopausal or postmenopausal stages,
• Menstrual cycles of less than 28 days,
• Started new medication within the last 3 months,
• Modifications to their existing treatment apart from taVNS.

Sponsors & Collaborators

• Fenerbahce University: lead

Study Sites (1)

Sancak Tıp Merkezi

Istanbul, Turkey (Türkiye)

Location

Related Publications (1)

• Akkurt MF, Ozden AV, Akkurt HE, Akkurt B, Bildik C. Effects of left and bilateral transcutaneous auricular vagus nerve stimulation on pain, mood, and autonomic nervous system in female patients with fibromyalgia: a randomized controlled trial. Physiother Theory Pract. 2025 Dec 2:1-11. doi: 10.1080/09593985.2025.2594572. Online ahead of print.

  PMID: 41332177 DERIVED

MeSH Terms

Conditions

Fibromyalgia

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PHD

Study Record Dates

• First Submitted: March 6, 2025
• First Posted: March 11, 2025
• Study Start: August 2, 2021
• Primary Completion: August 30, 2021
• Study Completion: October 31, 2022
• Last Updated: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

TU (1)