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

June 28, 2025 updated by: Burcu AKKURT, Fenerbahce University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Turkey
      • Istanbul, Turkey
        • Sancak Tıp Merkezi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Left taVNS
Left taVNS group received taVNS stimulation through the left ear for 11 sessions.
Device: Transcutaneous Auricular Vagus Nerve Stimulation
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.
Active Comparator: Bilateral taVNS
Bilateral taVNS group received taVNS stimulation through the bilateral ears for 11 sessions.
Device: Transcutaneous Auricular Vagus Nerve Stimulation
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fibromyalgia Impact Questionnaire
Time Frame: From enrollment to the 28th day of control
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
PNS Index Activity
Time Frame: From enrollment to the 28th day of control
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
Time Frame: From enrollment to the 28th day of control
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
Visual Analog Scale
Time Frame: From enrollment to the 28th day of control
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
Assessment of Autonomic Nervous System Activity (SNS and PNS Index)
Time Frame: From enrollment to the 28th day of control

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Beck Depression Index
Time Frame: From enrollment to the 28th day of control
The Beck Depression Index (BDI) is an evaluation questionnaire that assesses, behavioral signs of depression in adolescents and adults. The total score ranges from 0 to 63. It is interpreted as Minimal =0-9, Mild=10-16, Moderate=17-29 and Severe=30-63.
From enrollment to the 28th day of control
Beck Anxiety Inventory
Time Frame: From enrollment to the 28th day of control
The Beck Anxiety Inventory (BAI) is suggested as a tool for evaluating clinical anxiety and distinguishing between anxious and non-anxious diagnostic groups. It is a 21-item Likert-type scale, scored from 0 to 3. The total score ranges from 0 to 63, with the following classifications: mild <21, moderate: 22-35, and severe>36
From enrollment to the 28th day of control

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fenerbahce University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 2, 2021

Primary Completion (Actual)

August 30, 2021

Study Completion (Actual)

October 31, 2022

Study Registration Dates

First Submitted

March 6, 2025

First Submitted That Met QC Criteria

March 6, 2025

First Posted (Actual)

March 11, 2025

Study Record Updates

Last Update Posted (Actual)

July 2, 2025

Last Update Submitted That Met QC Criteria

June 28, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12.08.2021/31

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Only IPD used in the results publication.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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