The Effect of Vagus Nerve Stimulation on Pain and Functional Activities in Individuals With Chronic Widespread Pain

NCT07080749 | Not Yet Recruiting

• 1 other identifier: IRB Number 2025-048
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Widspread Chronic Pain, Fibromyalgia

Keywords

Vagal Nerve Stimulation; Deep Exhalation; Ear Electrical Stimulation; Chronic Pain; Central Sensitization

Outcome Measures

Primary Outcomes (16)

• 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).

  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)

  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).

  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).

  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).

  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).

  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)

  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)

  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)

  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).

  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)

  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).

  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).

  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).

  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).

  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).

  Baseline, after 2 weeks and after 8 weeks

Secondary Outcomes (5)

• Quality of Life (Quality of Life Scale - QOLS)

  From enrollment to the end of treatment period at 2 weeks.

• Positive Affect Score (PANAS)

  From enrollment to the end of treatment period at 2 weeks

• Depression Severity (Patient Health Questionnaire-9)

  From enrollment to the of treatment period at 2 weeks

• Negative Affect Score (Positive and Negative Affect Schedule - PANAS)

  From enrollment to the end of treatment at 8 weeks

• Muscle Creep/Compliance

  From enrollment to the end of treatment at 8 weeks

Study Arms (3)

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.

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.

Other: Vagal nerve stimulation through ear electrical stimulation

No intervention

OTHER

Participants in this group will not receive any treatment for vagal nerve stimulation.

Other: No intervention (observational study)

Interventions

Vagal nerve stimulation through deep exhalation exercise OTHER

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 deep exhalation.

Vagal nerve stimulation through ear electrical stimulation OTHER

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.

Vagal Nerve Stimulation through ear electrical stimulation

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.

No intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 18 years of age or older
• Diagnosed by a healthcare provider with chronic widespread pain or fibromyalgia

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of North Georgia: lead

Study Sites (1)

University of North Georgia

Dahlonega, Georgia, 30597, United States

Location

MeSH Terms

Conditions

Fibromyalgia; Chronic Pain

Interventions

Observation

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Central Study Contacts

Mohammad Reza Nourbakhsh, PT, Ph.D.

CONTACT

706 864 1766; Reza.nourbakhsh@ung.edu

Rachael Wlton-Mouw, PT, DPT

CONTACT

706 867 3086; rachael.waltonmouw@ung.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Physical Therapy

Study Record Dates

• First Submitted: July 3, 2025
• First Posted: July 23, 2025
• Study Start: August 30, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 6 months after publication with no end date
• Access Criteria: A data sharing agreement must be signed

Locations

US (1)