Widspread Chronic Pain, FibromyalgiaNCT07080749
The Effect of Vagus Nerve Stimulation on Pain and Functional Activities in Individuals With Chronic Widespread Pain
A study testing Vagal nerve stimulation through deep exhalation exercise and Vagal nerve stimulation through ear electrical stimulation in people with Widspread Chronic Pain, Fibromyalgia, run by University of North Georgia at 1 site in United States.
Trial summary
The goal of this clinical trial is to examine the effect of vagus nerve stimulation (VNS) on chronic, widespread pain in adults. The study will also evaluate which method of VNS-electrical ear stimulation or deep exhalation breathing-has a more significant impact on pain intensity, quality of life, and emotional… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Widspread Chronic Pain, Fibromyalgia
- What is being tested?
- Vagal nerve stimulation through deep exhalation exercise and Vagal nerve stimulation through ear electrical stimulation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Aug 2025to 30 Aug 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults 18 years of age or older
- Diagnosed by a healthcare provider with chronic widespread pain or fibromyalgia
Who cannot join
- Cardiovascular disorders: Such as arrhythmia (irregular heartbeat), heart failure, coronary artery disease, or history of heart surgery
- Neurological disorders: Including epilepsy, Parkinson's disease, multiple sclerosis, neuropathy, or seizures
- Endocrine disorders: Such as uncontrolled diabetes, thyroid disease (hypothyroidism or hyperthyroidism), or adrenal disorders
- Gastrointestinal disorders: Including inflammatory bowel disease (Crohn's disease, ulcerative colitis), irritable bowel syndrome, or chronic acid reflux (GERD)
- Respiratory disorders: Such as asthma, chronic bronchitis, emphysema, or sleep apnea
- Vestibular disorders: Including Meniere's disease, benign paroxysmal positional vertigo (BPPV), or any condition causing balance problems
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- History of concussion or traumatic brain injury
- Frequent dizziness or vertigo: History of unexplained or recurring episodes
- Chronic or recurrent headaches: Including migraines, tension-type headaches, or cluster headaches
- Ear problems: History of ear infections, hearing loss, tinnitus (ringing in the ears), or ear surgeries
- Throat problems: History of chronic sore throat, difficulty swallowing (dysphagia), or throat surgery
- Herniation: History of any type of herniation such as spinal disc herniation, inguinal (groin) hernia, or abdominal hernia
- Skin sensitivity to electrical stimulation: Known allergic reaction, rash, or irritation from electrode pads or electrical devices applied to the skin
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of North Georgia
Dahlonega, Georgia, 30597
Ruth Mahr, PT, Ph.D., 706 867 2945, ruth.maher@ung.edu
Tamara Paal, 706 867 2747, tamara.paal@ung.edu
About this study
Official title: The Effects of Vagus Nerve Stimulation on Pain, Muscle Stiffness, Heart Rate, And Functional Activities in Individuals With Chronic Widespread Pain - A Double Blinded Randomized Control Trial
The goal of this clinical trial is to examine the effect of vagus nerve stimulation (VNS) on chronic, widespread pain in adults. The study will also evaluate which method of VNS-electrical ear stimulation or deep exhalation breathing-has a more significant impact on pain intensity, quality of life, and emotional well-being.
The main questions it aims to answer are:
Read more
Does vagus nerve stimulation reduce pain intensity in individuals with chronic, widespread pain?
Which intervention-electrical ear stimulation or deep exhalation breathing-provides a greater improvement in autonomic function, emotional status, and quality of life?
Researchers will compare two active interventions-electrical ear stimulation and deep exhalation breathing-to a no-treatment control group to determine relative effectiveness on pain and related outcomes.
Participants will:
Be randomly assigned to one of three groups:
- Electrical Ear Stimulation: Apply a small, non-invasive device to the ear for 20 minutes, twice daily for two weeks.
- Deep Exhalation Breathing: Perform balloon-blowing exercises (four deep exhalations per set) once every waking hour each day for two weeks.
- Control Group: Receive no intervention during the two-week period. These participants will complete baseline testing, return after two weeks for follow-up testing, and then be debriefed. They will have the option to withdraw or receive an active treatment after study data collection concludes.
Complete four questionnaires to assess pain, emotional state, and quality of life.
Undergo physiological assessments including heart rate variability, neck muscle tissue flexibility (via MyotonPro), and pressure pain sensitivity (via pressure algometer), both before and after the 2-week period.
Participation includes two in-person sessions (approximately 1 hour each) and daily home practice (for intervention groups) lasting 40-60 minutes per day for two weeks. The study involves minimal risk, and no compensation is provided. Participation is voluntary, and confidentiality will be strictly maintained.
Read the detailed description
Detailed Description:
Study Overview:
This randomized controlled clinical trial investigates the effects of two forms of non-invasive vagus nerve stimulation (VNS) on chronic widespread pain (CWP). The study is designed to explore whether stimulating the vagus nerve through auricular electrical stimulation (AES) or deep forced exhalation (DFE) improves pain, muscle stiffness, and functional status in individuals with CWP.
Vagal nerve stimulation (VNS) has been associated with modulation of the autonomic nervous system, leading to downstream effects on inflammation, pain perception, and emotional regulation. This study compares the effectiveness of these two intervention methods with a control group that receives no treatment during the study period.
Research Questions:
- Does VNS via deep forced exhalation improve pain, muscle stiffness, and functional outcomes in individuals with chronic widespread pain?
- Does VNS via auricular electrical stimulation improve these same outcomes?
- Is one intervention more effective than the other in improving autonomic and pain-related parameters?
Hypotheses:
- Null Hypothesis: Neither deep forced exhalation nor auricular electrical stimulation will produce significant improvements in pain, muscle stiffness, or functional capacity.
- Alternative Hypothesis: Both interventions will lead to significant improvements in pain, muscle stiffness, and functional outcomes compared to a control group.
Study Procedures and Assessments:
Participants will be randomly assigned to one of three groups:
- Auricular Electrical Stimulation (AES)
- Deep Forced Exhalation (DFE)
- No-Treatment Control Each participant will undergo the same battery of assessments at baseline and after the two-week intervention or observation period.
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- Heart Rate Variability (HRV): Assessed using the Polar H10 chest strap sensor.
- Equipment preparation: The investigator ensures the Polar H10 sensor and strap are clean and functional. Electrode areas are moistened with water or gel to improve signal quality. Bluetooth is enabled on the recording device (e.g., smartphone).
- Participant setup: Participants wear clothing allowing chest access. The chest strap is positioned snugly around the torso, just below the chest muscles and centered on the sternum. The Polar H10 sensor is connected to the chest strap for data collection. and ensure it activates (indicated by a blinking LED light).
- Data collection: The participant sits in a relaxed upright posture in a quiet, temperature-controlled room. After a 5-minute acclimation period, HRV data is recorded for 10 minutes. Participants are instructed not to talk, move, or use electronic devices during this time.
- Muscle Stiffness and Tissue Compliance: Measured using the MyotonPRO device on the upper trapezius. • Equipment preparation: The MyotonPRO is calibrated before each session.
- Participant setup: The participant wears clothing that allows shoulder access and avoids caffeine, alcohol, or vigorous activity for at least 2 hours prior. The participant lies supine for at least 5 minutes before testing.
- Measurement: The skin is cleaned and the midpoint of the trapezius marked. The probe is placed perpendicular to the skin, and 3-5 consecutive measurements are taken on each side. The device records stiffness (N/m), elasticity, relaxation time, frequency, and compliance. Data is stored under a participant ID for analysis.
- Pain Pressure Threshold (PPT): Assessed with a handheld analog pressure algometer at three locations: mid trapezius, L5 lumbar paraspinal, and gastrocnemius-soleus junction.
- Setup: The participant avoids caffeine, alcohol, and intense activity for at least 2-3 hours. They rest for 5-10 minutes in a quiet room before testing.
- Protocol: Skin is marked, and the procedure is explained. Pressure is applied at ~30 kPa/sec until the participant signals when it transitions to pain. Three trials are performed at each site with 30-60 second rests. The average of three values is recorded.
- Pain Level: Measured using the Visual Analog Scale (VAS), a 10 cm line from "no pain" to "worst pain imaginable."
- Quality of Life: Measured with the Quality of Life Scale (QOLS), covering physical, emotional, and social domains.
- Emotional State: Assessed using the Positive and Negative Affect Schedule (PANAS), which rates 10 positive and 10 negative emotions.
- Depression Severity:
Evaluated using the Patient Health Questionnaire-9 (PHQ-9), a 9-item tool commonly used in research and clinical practice.
Intervention Protocols:
- Auricular Electrical Stimulation (AES):
- Objective: Stimulate the auricular branch of the vagus nerve (ABVN) using taVNS.
- Site: Cymba conchae of the left ear.
- Equipment: Standard taVNS device, clip electrodes with conductive gel, timer, and alcohol swabs.
- Stimulation Parameters:
- Waveform: Biphasic rectangular
- Pulse width: 200-300 µs
- Frequency: 20 Hz
- Intensity: Starting at 0.1 mA, increased until tingling is comfortable but not painful
- Duration: 20 minutes per session, twice daily for 2 weeks
- Contraindications: Cardiac arrhythmia, implanted pacemakers, pregnancy, epilepsy, skin infection at site, metal implants near ear.
- Procedure: First session is supervised. Participants are trained to apply the device at home. Instructions emphasize safety, comfort, and proper use. Participants remain seated or semi-reclined during stimulation, and are instructed to avoid standing or walking while stimulated.
- Deep Forced Exhalation (DFE):
- Objective: Stimulate vagal tone through autonomic regulation via breathwork.
- Equipment: Latex-free balloons and logbook.
- Procedure: Participants take a deep breath, blow continuously into the balloon, then block airflow with the tongue. This is repeated for 4 breaths. The procedure is practiced once per hour during waking hours. Participants sit comfortably and avoid physical strain.
- Control Group:
Participants undergo all pre- and post-study assessments but receive no intervention during the two-week period. They are debriefed afterward and may opt to receive either treatment following data collection.
Safety Considerations:
Potential AES risks include local irritation, tingling, warmth, lightheadedness, or bradycardia. All participants are screened and monitored during the first session. Instructions emphasize safe positioning, hydration, and gradual adjustment of intensity. Participants are advised to stop the session and contact the research team if they feel unwell.
DFE carries low risk, with occasional lightheadedness or fatigue reported. This is minimized by recommending seated practice and gradual breath intensity. Participants are asked to rest after each session.
Expected Benefits:
Participants may experience decreased pain sensitivity, improved autonomic regulation, better emotional well-being, and improved quality of life. These outcomes are not guaranteed, and no monetary compensation is offered for participation.
Contact Information:
Dr. Reza Nourbakhsh Email: Reza.nourbakhsh@ung.edu Phone: 706-864-1766
- Conditions
- Widspread Chronic Pain, Fibromyalgia
- Being tested
- Vagal nerve stimulation through deep exhalation exercise, Vagal nerve stimulation through ear electrical stimulation, No intervention (observational study)
- Keywords
- Vagal Nerve Stimulation, Deep Exhalation, Ear Electrical Stimulation, Chronic Pain, Central Sensitization
- Medical subject headings
- Fibromyalgia, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vagal nerve stimulation through deep exhalation exerciseOther
Deep Exhalation Treatment: Participants will receive a set of standard balloons to use for deep exhalation. They will sit in a comfortable position, take a deep breath in and blow their breath continuously out into the balloon. They repeat the deep exhalation process for a total of 4 consecutive breaths. They perform this breathing exercise once every hour during waking hours each day.
Vagal nerve stimulation through ear electrical stimulationOther
Ear Electrical Stimulation Treatment: Participants will receive a small electrical stimulator and electrode set to be applied to their left ear. The investigators will train the participants to use the device safely and effectively. Once they are comfortable with the procedure, they will perform the procedure at home for 20 minutes twice daily.
No intervention (observational study)Other
The no intervention group will not receive treatment immediately after their baseline assessments, they will be scheduled for another visit after two weeks, then a new set of baseline measurements will be recorded as the post intervention data.
| Study group | Role | What they receive |
|---|---|---|
| Vagal Nerve Stimulation through deep exhalation. | Active comparator | Vagal nerve stimulation will be performed through deep exhalation exercise, performed once every hour during the waking hours each day. Receives: Other: Vagal nerve stimulation through deep exhalation exercise |
| Vagal Nerve Stimulation through ear electrical stimulation | Active comparator | Vagal nerve stimulation will be performed through applying low frequency electrical stimulation to the external ear lobe for 20 minutes twice a day. Receives: Other: Vagal nerve stimulation through ear electrical stimulation |
| No intervention | Other | Participants in this group will not receive any treatment for vagal nerve stimulation. Receives: Other: No intervention (observational study) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain Intensity
Pain intensity will be assessed using the Visual Analog Scale (VAS), a 10 cm horizontal line anchored by "no pain" and "worst imaginable pain." Participants mark their current level of pain on the line, which is measured in centimeters (cm).
Measured: From enrollment to the end of treatment at 2 weeks
Muscle stiffness
Muscle stiffness, defined as the resistance of the tissue to an external force, will be measured in the upper trapezius using the MyotonPro device. Stiffness reflects the biomechanical integrity of muscle tissue. Unit of Measure: Newtons per meter (N/m)
Measured: Frome enrollment to the end of treatment at 8 weeks
Pressure Pain Threshold - Trapezius muscle
Pressure pain threshold (PPT) at the mid-belly of the upper trapezius will be assessed using a calibrated analog pressure algometer. PPT is defined as the minimum force required to elicit pain and reflects mechanical pain sensitivity. Unit of Measure: Kilograms per square centimeter (kg/cm²).
Measured: From enrollment to the end of treatment period at 2 weeks
SDNN (Standard Deviation of NN intervals)
SDNN will be used to assess overall heart rate variability, reflecting both sympathetic and parasympathetic nervous system activity over a 10-minute resting period. Unit of Measure: milliseconds (ms).
Measured: From enrollment to the end of treatment at 2 weeks
Mechanical Stress Relaxation Time
Mechanical Stress Relaxation Time, defined as the time required for tissue to return to its original state following a mechanical impulse, will be measured using the MyotonPro device. This parameter reflects the viscoelastic properties of skeletal muscle. Unit of Measure: milliseconds (ms).
Measured: From enrollment to the end of treatment at 8 weeks
Muscle Oscillation Frequency
Frequency, representing the natural oscillation frequency of muscle tissue in response to a brief mechanical impulse, will be measured using the MyotonPro device. It reflects the intrinsic muscle tone and biomechanical behavior of the tissue. Unit of Measure: Hertz (Hz).
Measured: From enrollment to the end of treatment at 8 weeks.
Pressure Pain Threshold - Lumbar Paraspinal Muscles
PPT at the lumbar paraspinal region (L5 level) will be measured using an analog pressure algometer to assess localized pain sensitivity. Unit of measurement: Kilograms per square centimeter (kg/cm²)
Measured: From enrollment to the end of treatment at 8 weeks
Pressure Pain Threshold - Calf Muscles
PPT at the junction of the gastrocnemius and soleus muscles in the calf will be measured using a pressure algometer to evaluate distal pain sensitivity. Unit of Measure: Kilograms per square centimeter (kg/cm²)
Measured: From enrollment to the end of treatment at 8 weeks
Muscle Elasticity (Logarithmic Decrement)
Elasticity, measured as logarithmic decrement, describes the ability of muscle tissue to return to its original shape after deformation. It will be measured using the MyotonPro on the upper trapezius. Lower values indicate greater elasticity. Unit of Measure: Unitless (logarithmic decrement)
Measured: From enrollment to the end of treatment at 8 weeks
RMSSD (Root Mean Square of Successive Differences)
RMSSD will be used as a marker of short-term parasympathetic activity. Unit of Measure: milliseconds (ms).
Measured: Baseline, after 2 weeks and after 8 weeks
SDANN (Standard Deviation of Average NN intervals)
SDANN will be used to evaluate longer-term components of heart rate variability associated with sympathetic activity. Unit of Measure: milliseconds (ms)
Measured: Baseline, after 2 weeks, and after 8 weeks
LF Power (Low Frequency Power)
LF Power will be analyzed to assess contributions from both sympathetic and parasympathetic nervous systems in frequency domain. Unit of Measure: milliseconds² (ms²).
Measured: Baseline, after 2 weeks and after 8 weeks
HF Power (High Frequency Power)
HF Power will be measured to evaluate parasympathetic (vagal) nervous system activity. Unit of Measure: milliseconds² (ms²).
Measured: Baseline, after 2 weeks and after 8 weeks
LF/HF Ratio
LF/HF ratio will be used as a marker of autonomic balance, indicating the relative influence of sympathetic to parasympathetic tone. Unit of Measure: Ratio (unitless).
Measured: Baseline, after 2 weeks and after 8 weeks
VLF Power (Very Low Frequency Power)
VLF Power will be measured to assess longer-term regulatory systems, including thermoregulation and hormonal factors. Unit of Measure: milliseconds² (ms²).
Measured: Baseline, after 2 weeks and after 8 weeks
ULF Power (Ultra Low Frequency Power)
ULF Power will be assessed to capture circadian and ultradian influences on autonomic regulation. Unit of Measure: milliseconds² (ms²).
Measured: Baseline, after 2 weeks and after 8 weeks
Secondary outcomes (5)
Quality of Life (Quality of Life Scale - QOLS)
The Quality of Life Scale (QOLS) will be used to evaluate participants' perceived well-being and life satisfaction across physical, social, and personal domains. The scale includes 16 items scored from 1 to 7, with total scores ranging from 16 to 112. Unit of Measure: Total score (range: 16-112). Higher scores indicate better quality of life.
Measured: From enrollment to the end of treatment period at 2 weeks.
Positive Affect Score (PANAS)
The Positive and Negative Affect Schedule (PANAS) will be used to assess emotional state. The positive affect subscale contains 10 items, each rated from 1 (very slightly or not at all) to 5 (extremely), yielding scores from 10 to 50. Unit of Measure: Total score (range: 10-50). Higher scores indicate a higher level of positive emotional state.
Measured: From enrollment to the end of treatment period at 2 weeks
Depression Severity (Patient Health Questionnaire-9)
The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-report scale measuring depression symptom severity. Each item is rated from 0 (not at all) to 3 (nearly every day), with a total score ranging from 0 to 27. Unit of Measure: Total score (range: 0-27). Higher scores indicate more severe depressive symptoms.
Measured: From enrollment to the of treatment period at 2 weeks
Negative Affect Score (Positive and Negative Affect Schedule - PANAS)
The PANAS negative affect subscale consists of 10 items, each scored from 1 to 5, with a total score ranging from 10 to 50. This subscale measures levels of distress and negative emotionality. Unit of Measure: Total score (range: 10-50). Higher scores indicate greater negative emotional states.
Measured: From enrollment to the end of treatment at 8 weeks
Muscle Creep/Compliance
Creep (or compliance), representing the viscoelastic behavior of muscle over time, will be assessed using the MyotonPro device. This parameter reflects the ability of muscle tissue to deform gradually under sustained stress. Unit of Measure: Deborah number (or dimensionless unit, based on device output)
Measured: From enrollment to the end of treatment at 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2025
- Study start30 Aug 2025 (estimated)
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Widspread Chronic Pain, FibromyalgiaStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of North Georgia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohammad(Reza) Nourbakhsh, University of North Georgia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07080749
- Sponsor's protocol ID
- IRB Number 2025-048
- Status last verified
- Jul 2025
- First submitted
- 3 Jul 2025
- Last updated
- 23 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD that underlie results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Vagus Nerve Stimulation on Pain, Muscle Stiffness, Heart Rate, And Functional Activities in Individuals With Chronic Widespread Pain - A Double Blinded Randomized Control Trial
- ClinicalTrials.gov ID
- NCT07080749
- Acronym / sponsor ID
- IRB Number 2025-048
- Conditions
- Widspread Chronic Pain, Fibromyalgia
- Keywords
- Vagal Nerve Stimulation, Deep Exhalation, Ear Electrical Stimulation, Chronic Pain, Central Sensitization
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of North GeorgiaUniversity, hospital or other
- Study start
- 30 Aug 2025 (estimated)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Aug 2026 (estimated)
- First posted
- 23 Jul 2025 (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.
The goal of this clinical trial is to examine the effect of vagus nerve stimulation (VNS) on chronic, widespread pain in adults. The study will also evaluate which method of VNS-electrical ear stimulation or deep exhalation breathing-has a more significant impact on pain intensity, quality of life, and emotional well-being.
The main questions it aims to answer are:
Does vagus nerve stimulation reduce pain intensity in individuals with chronic, widespread pain?
Which intervention-electrical ear stimulation or deep exhalation breathing-provides a greater improvement in autonomic function, emotional status, and quality of life?
Researchers will compare two active interventions-electrical ear stimulation and deep exhalation breathing-to a no-treatment control group to determine relative effectiveness on pain and related outcomes.
Participants will:
Be randomly assigned to one of three groups:
- Electrical Ear Stimulation: Apply a small, non-invasive device to the ear for 20 minutes, twice daily for two weeks.
- Deep Exhalation Breathing: Perform balloon-blowing exercises (four deep exhalations per set) once every waking hour each day for two weeks.
- Control Group: Receive no intervention during the two-week period. These participants will complete baseline testing, return after two weeks for follow-up testing, and then be debriefed. They will have the option to withdraw or receive an active treatment after study data collection concludes.
Complete four questionnaires to assess pain, emotional state, and quality of life.
Undergo physiological assessments including heart rate variability, neck muscle tissue flexibility (via MyotonPro), and pressure pain sensitivity (via pressure algometer), both before and after the 2-week period.
Participation includes two in-person sessions (approximately 1 hour each) and daily home practice (for intervention groups) lasting 40-60 minutes per day for two weeks. The study involves minimal risk, and no compensation is provided. Participation is voluntary, and confidentiality will be strictly maintained.
Detailed description
Detailed Description:
Study Overview:
This randomized controlled clinical trial investigates the effects of two forms of non-invasive vagus nerve stimulation (VNS) on chronic widespread pain (CWP). The study is designed to explore whether stimulating the vagus nerve through auricular electrical stimulation (AES) or deep forced exhalation (DFE) improves pain, muscle stiffness, and functional status in individuals with CWP.
Vagal nerve stimulation (VNS) has been associated with modulation of the autonomic nervous system, leading to downstream effects on inflammation, pain perception, and emotional regulation. This study compares the effectiveness of these two intervention methods with a control group that receives no treatment during the study period.
Research Questions:
- Does VNS via deep forced exhalation improve pain, muscle stiffness, and functional outcomes in individuals with chronic widespread pain?
- Does VNS via auricular electrical stimulation improve these same outcomes?
- Is one intervention more effective than the other in improving autonomic and pain-related parameters?
Hypotheses:
- Null Hypothesis: Neither deep forced exhalation nor auricular electrical stimulation will produce significant improvements in pain, muscle stiffness, or functional capacity.
- Alternative Hypothesis: Both interventions will lead to significant improvements in pain, muscle stiffness, and functional outcomes compared to a control group.
Study Procedures and Assessments:
Participants will be randomly assigned to one of three groups:
- Auricular Electrical Stimulation (AES)
- Deep Forced Exhalation (DFE)
- No-Treatment Control Each participant will undergo the same battery of assessments at baseline and after the two-week intervention or observation period.
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- Heart Rate Variability (HRV): Assessed using the Polar H10 chest strap sensor.
- Equipment preparation: The investigator ensures the Polar H10 sensor and strap are clean and functional. Electrode areas are moistened with water or gel to improve signal quality. Bluetooth is enabled on the recording device (e.g., smartphone).
- Participant setup: Participants wear clothing allowing chest access. The chest strap is positioned snugly around the torso, just below the chest muscles and centered on the sternum. The Polar H10 sensor is connected to the chest strap for data collection. and ensure it activates (indicated by a blinking LED light).
- Data collection: The participant sits in a relaxed upright posture in a quiet, temperature-controlled room. After a 5-minute acclimation period, HRV data is recorded for 10 minutes. Participants are instructed not to talk, move, or use electronic devices during this time.
- Muscle Stiffness and Tissue Compliance: Measured using the MyotonPRO device on the upper trapezius. • Equipment preparation: The MyotonPRO is calibrated before each session.
- Participant setup: The participant wears clothing that allows shoulder access and avoids caffeine, alcohol, or vigorous activity for at least 2 hours prior. The participant lies supine for at least 5 minutes before testing.
- Measurement: The skin is cleaned and the midpoint of the trapezius marked. The probe is placed perpendicular to the skin, and 3-5 consecutive measurements are taken on each side. The device records stiffness (N/m), elasticity, relaxation time, frequency, and compliance. Data is stored under a participant ID for analysis.
- Pain Pressure Threshold (PPT): Assessed with a handheld analog pressure algometer at three locations: mid trapezius, L5 lumbar paraspinal, and gastrocnemius-soleus junction.
- Setup: The participant avoids caffeine, alcohol, and intense activity for at least 2-3 hours. They rest for 5-10 minutes in a quiet room before testing.
- Protocol: Skin is marked, and the procedure is explained. Pressure is applied at ~30 kPa/sec until the participant signals when it transitions to pain. Three trials are performed at each site with 30-60 second rests. The average of three values is recorded.
- Pain Level: Measured using the Visual Analog Scale (VAS), a 10 cm line from "no pain" to "worst pain imaginable."
- Quality of Life: Measured with the Quality of Life Scale (QOLS), covering physical, emotional, and social domains.
- Emotional State: Assessed using the Positive and Negative Affect Schedule (PANAS), which rates 10 positive and 10 negative emotions.
- Depression Severity:
Evaluated using the Patient Health Questionnaire-9 (PHQ-9), a 9-item tool commonly used in research and clinical practice.
Intervention Protocols:
- Auricular Electrical Stimulation (AES):
- Objective: Stimulate the auricular branch of the vagus nerve (ABVN) using taVNS.
- Site: Cymba conchae of the left ear.
- Equipment: Standard taVNS device, clip electrodes with conductive gel, timer, and alcohol swabs.
- Stimulation Parameters:
- Waveform: Biphasic rectangular
- Pulse width: 200-300 µs
- Frequency: 20 Hz
- Intensity: Starting at 0.1 mA, increased until tingling is comfortable but not painful
- Duration: 20 minutes per session, twice daily for 2 weeks
- Contraindications: Cardiac arrhythmia, implanted pacemakers, pregnancy, epilepsy, skin infection at site, metal implants near ear.
- Procedure: First session is supervised. Participants are trained to apply the device at home. Instructions emphasize safety, comfort, and proper use. Participants remain seated or semi-reclined during stimulation, and are instructed to avoid standing or walking while stimulated.
- Deep Forced Exhalation (DFE):
- Objective: Stimulate vagal tone through autonomic regulation via breathwork.
- Equipment: Latex-free balloons and logbook.
- Procedure: Participants take a deep breath, blow continuously into the balloon, then block airflow with the tongue. This is repeated for 4 breaths. The procedure is practiced once per hour during waking hours. Participants sit comfortably and avoid physical strain.
- Control Group:
Participants undergo all pre- and post-study assessments but receive no intervention during the two-week period. They are debriefed afterward and may opt to receive either treatment following data collection.
Safety Considerations:
Potential AES risks include local irritation, tingling, warmth, lightheadedness, or bradycardia. All participants are screened and monitored during the first session. Instructions emphasize safe positioning, hydration, and gradual adjustment of intensity. Participants are advised to stop the session and contact the research team if they feel unwell.
DFE carries low risk, with occasional lightheadedness or fatigue reported. This is minimized by recommending seated practice and gradual breath intensity. Participants are asked to rest after each session.
Expected Benefits:
Participants may experience decreased pain sensitivity, improved autonomic regulation, better emotional well-being, and improved quality of life. These outcomes are not guaranteed, and no monetary compensation is offered for participation.
Contact Information:
Dr. Reza Nourbakhsh Email: Reza.nourbakhsh@ung.edu Phone: 706-864-1766
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Vagal Nerve Stimulation through deep exhalation. | Active comparator | Other: Vagal nerve stimulation through deep exhalation exerciseVagal nerve stimulation will be performed through deep exhalation exercise, performed once every hour during the waking hours each day. |
| Vagal Nerve Stimulation through ear electrical stimulation | Active comparator | Other: Vagal nerve stimulation through ear electrical stimulationVagal nerve stimulation will be performed through applying low frequency electrical stimulation to the external ear lobe for 20 minutes twice a day. |
| No intervention | Other | Other: No intervention (observational study)Participants in this group will not receive any treatment for vagal nerve stimulation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adults 18 years of age or older
- Diagnosed by a healthcare provider with chronic widespread pain or fibromyalgia
Key exclusion criteria (13 listed)
- Cardiovascular disorders: Such as arrhythmia (irregular heartbeat), heart failure, coronary artery disease, or history of heart surgery
- Neurological disorders: Including epilepsy, Parkinson's disease, multiple sclerosis, neuropathy, or seizures
- Endocrine disorders: Such as uncontrolled diabetes, thyroid disease (hypothyroidism or hyperthyroidism), or adrenal disorders
- Gastrointestinal disorders: Including inflammatory bowel disease (Crohn's disease, ulcerative colitis), irritable bowel syndrome, or chronic acid reflux (GERD)
- Respiratory disorders: Such as asthma, chronic bronchitis, emphysema, or sleep apnea
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 |
|---|---|---|
| Vagal nerve stimulation through deep exhalation exerciseDeep Exhalation Treatment: Participants will receive a set of standard balloons to use for deep exhalation. They will sit in a comfortable position, take a deep breath in and blow their breath continuously out into the balloon. They repeat the deep exhalation process for a total of 4 consecutive breaths. They perform this breathing exercise once every hour during waking hours each day. | Other | Vagal Nerve Stimulation through deep exhalation. |
| Vagal nerve stimulation through ear electrical stimulationEar Electrical Stimulation Treatment: Participants will receive a small electrical stimulator and electrode set to be applied to their left ear. The investigators will train the participants to use the device safely and effectively. Once they are comfortable with the procedure, they will perform the procedure at home for 20 minutes twice daily. | Other | Vagal Nerve Stimulation through ear electrical stimulation |
| No intervention (observational study)The no intervention group will not receive treatment immediately after their baseline assessments, they will be scheduled for another visit after two weeks, then a new set of baseline measurements will be recorded as the post intervention data. | Other | No intervention |
Primary outcome
Pain Intensity
Time frame: From enrollment to the end of treatment at 2 weeks
Pain intensity will be assessed using the Visual Analog Scale (VAS), a 10 cm horizontal line anchored by "no pain" and "worst imaginable pain." Participants mark their current level of pain on the line, which is measured in centimeters (cm).
Muscle stiffness
Time frame: Frome enrollment to the end of treatment at 8 weeks
Muscle stiffness, defined as the resistance of the tissue to an external force, will be measured in the upper trapezius using the MyotonPro device. Stiffness reflects the biomechanical integrity of muscle tissue. Unit of Measure: Newtons per meter (N/m)
Pressure Pain Threshold - Trapezius muscle
Time frame: From enrollment to the end of treatment period at 2 weeks
Pressure pain threshold (PPT) at the mid-belly of the upper trapezius will be assessed using a calibrated analog pressure algometer. PPT is defined as the minimum force required to elicit pain and reflects mechanical pain sensitivity. Unit of Measure: Kilograms per square centimeter (kg/cm²).
SDNN (Standard Deviation of NN intervals)
Time frame: From enrollment to the end of treatment at 2 weeks
SDNN will be used to assess overall heart rate variability, reflecting both sympathetic and parasympathetic nervous system activity over a 10-minute resting period. Unit of Measure: milliseconds (ms).
Mechanical Stress Relaxation Time
Time frame: From enrollment to the end of treatment at 8 weeks
Mechanical Stress Relaxation Time, defined as the time required for tissue to return to its original state following a mechanical impulse, will be measured using the MyotonPro device. This parameter reflects the viscoelastic properties of skeletal muscle. Unit of Measure: milliseconds (ms).
Muscle Oscillation Frequency
Time frame: From enrollment to the end of treatment at 8 weeks.
Frequency, representing the natural oscillation frequency of muscle tissue in response to a brief mechanical impulse, will be measured using the MyotonPro device. It reflects the intrinsic muscle tone and biomechanical behavior of the tissue. Unit of Measure: Hertz (Hz).
Pressure Pain Threshold - Lumbar Paraspinal Muscles
Time frame: From enrollment to the end of treatment at 8 weeks
PPT at the lumbar paraspinal region (L5 level) will be measured using an analog pressure algometer to assess localized pain sensitivity. Unit of measurement: Kilograms per square centimeter (kg/cm²)
Pressure Pain Threshold - Calf Muscles
Time frame: From enrollment to the end of treatment at 8 weeks
PPT at the junction of the gastrocnemius and soleus muscles in the calf will be measured using a pressure algometer to evaluate distal pain sensitivity. Unit of Measure: Kilograms per square centimeter (kg/cm²)
Muscle Elasticity (Logarithmic Decrement)
Time frame: From enrollment to the end of treatment at 8 weeks
Elasticity, measured as logarithmic decrement, describes the ability of muscle tissue to return to its original shape after deformation. It will be measured using the MyotonPro on the upper trapezius. Lower values indicate greater elasticity. Unit of Measure: Unitless (logarithmic decrement)
RMSSD (Root Mean Square of Successive Differences)
Time frame: Baseline, after 2 weeks and after 8 weeks
RMSSD will be used as a marker of short-term parasympathetic activity. Unit of Measure: milliseconds (ms).
SDANN (Standard Deviation of Average NN intervals)
Time frame: Baseline, after 2 weeks, and after 8 weeks
SDANN will be used to evaluate longer-term components of heart rate variability associated with sympathetic activity. Unit of Measure: milliseconds (ms)
LF Power (Low Frequency Power)
Time frame: Baseline, after 2 weeks and after 8 weeks
LF Power will be analyzed to assess contributions from both sympathetic and parasympathetic nervous systems in frequency domain. Unit of Measure: milliseconds² (ms²).
HF Power (High Frequency Power)
Time frame: Baseline, after 2 weeks and after 8 weeks
HF Power will be measured to evaluate parasympathetic (vagal) nervous system activity. Unit of Measure: milliseconds² (ms²).
LF/HF Ratio
Time frame: Baseline, after 2 weeks and after 8 weeks
LF/HF ratio will be used as a marker of autonomic balance, indicating the relative influence of sympathetic to parasympathetic tone. Unit of Measure: Ratio (unitless).
VLF Power (Very Low Frequency Power)
Time frame: Baseline, after 2 weeks and after 8 weeks
VLF Power will be measured to assess longer-term regulatory systems, including thermoregulation and hormonal factors. Unit of Measure: milliseconds² (ms²).
ULF Power (Ultra Low Frequency Power)
Time frame: Baseline, after 2 weeks and after 8 weeks
ULF Power will be assessed to capture circadian and ultradian influences on autonomic regulation. Unit of Measure: milliseconds² (ms²).
5 secondary outcomes
Quality of Life (Quality of Life Scale - QOLS)
Time frame: From enrollment to the end of treatment period at 2 weeks.
Positive Affect Score (PANAS)
Time frame: From enrollment to the end of treatment period at 2 weeks
Depression Severity (Patient Health Questionnaire-9)
Time frame: From enrollment to the of treatment period at 2 weeks
Negative Affect Score (Positive and Negative Affect Schedule - PANAS)
Time frame: From enrollment to the end of treatment at 8 weeks
Muscle Creep/Compliance
Time frame: From enrollment to the end of treatment at 8 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2025.
- Individual participant dataSharing planned: Yes. IPD that underlie results in a publication
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vagal nerve stimulation through deep exhalation exercise and Vagal nerve stimulation through ear electrical stimulation in people with Widspread Chronic Pain, Fibromyalgia, run by University of North Georgia at 1 site in United States.
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 2 inclusion and 13 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: opening soon, as of the sponsor's last update on 23 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohammad Reza Nourbakhsh, PT, Ph.D. (706 864 1766, Reza.nourbakhsh@ung.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain Intensity (time frame: From enrollment to the end of treatment at 2 weeks). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jul 2025.