Transcutaneous Vagus Nerve Stimulation on Fibromyalgia- Double-blind, Sham-controlled Randomized Clinical Trial

NCT06912334 | Recruiting DMC

• 1 other identifier: 566/21-020-2024
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Stimulation of the vagus nerve, a parasympathetic nerve that controls the digestive, the vascular and immune systems, produces pain relief in various clinical conditions. Transmission via vagal afferents to the nucleus of the solitary tract has been proposed as the primary physiological mechanism that reduces pain intensity following vagal stimulation. Medication is one of the pillars of dealing with chronic pain, with several benefits, but also side effects. Fibromyalgia is an idiopathic chronic pain syndrome with few, effective and safe treatments. However, current research in the field of vagal innervation suggests psychophysiological and electrical ways by which the syndrome may be treated.The chronic pain symptoms of fibromyalgia patients may benefit from vagus nerve stimulation, by normalizing the autonomic and immune system dysfunction that causes their respective symptoms. However, the effects of multiple sessions of transcutaneous vagus nerve stimulation (tVNS) in fibromyalgia have not been evaluated in randomized clinical trials. The hypothesis of our study is to evaluate if the addition of transcutaneous stimulation of the auricular branch of the vagus nerves in patients with fibromyalgia, can lead to better pain control and quality of life. We will offer a 2-week treatment (14 sessions of 30 minutes) in a randomized double-blind controlled trial. The sample of the study, which will be conducted in the pain clinic of the Aretaieion University General Hospital, will be consisted of 120 patients, who will be divided into 2 groups (1st group: standard pharmacological treatment + active tVNS, 2nd group: standard pharmacological treatment + sham tVNS). The study is designed to determine, if standard pharmacological treatment combined with 14 sessions of tVNS is able to improve pain symptomatology in fibromyalgia and all symptoms of this syndrome, by using appropriate scales. This study examines a new and potentially impactful way to address a major public health issue where prevalence is high in given groups, its impact is multidimensional and treatment options are limited. The holistic treatment of chronic pain, including its neurobiological, cognitive, behavioral and psychological components, may become a valuable aid in the completion of the research project, with the ultimate aim of the study being the establishment of non-invasive stimulation of the vagus nerve for the treatment of chronic pain in clinical practice in the future.

Conditions

Transcutaneous Vagus Nerve Stimulation on Fibromyalgia

Keywords

vagus nerve; vagus nerve stimulation; tVNS; transcutaneous vagus nerve stimulation; fibromyalgia; FM; double blind; sham controlled; randomized clinical trial; pain; depression; sleep disorders; fatigue; fibro fog; 2016 revised FM ACR Classification Criteria

Outcome Measures

Primary Outcomes (1)

• Pain intensity and Fibromyalgia symptoms

  numerical rating scale pain score (NRS) and Brief Pain Inventory (BPI) and Fibromyalgia Symptoms according to 2016 FM ACR Classification Criteria

  2 weeks

Secondary Outcomes (5)

• Fatique

  2 weeks

• Depression

  2 weeks

• Sleep Disorders

  2 weeks

• Fibro Fog

  2 weeks

• Fibromyalgia Symptoms

  2 weeks

Study Arms (2)

active tVNS group

ACTIVE COMPARATOR

1st group Standard pharmacological Treatment according to EULAR + active tVNS, 30min/session, 7 days/week for 2 weeks (14 sessions total) Regarding the standard pharmacological treatment we will follow a stepwise approach according to the EULAR (European League Against Rheumatism) recommendations. The patients will be randomized by using randomization.org

Device: tVNS

sham tVNS group

SHAM COMPARATOR

2nd group Standard pharmacological Treatment according to EULAR + sham tVNS, 30min/session, 7 days/week for 2 weeks (14 sessions total) Regarding the standard pharmacological treatment we will follow a stepwise approach according to the EULAR (European League Against Rheumatism) recommendations. The patients will be randomized by using randomization.org

Device: tVNS

Interventions

tVNS DEVICE

tVNS L is a battery-driven electrical stimulator connected to an ear electrode which is positioned over the skin of the cymba conchae. Thus, auricular vagal stimulation will be applied using the typical ear electrodes of the tVNS® L device. tVNS will be applied over the left branch for safety reasons. For sham auricular tVNS, the anodal electrode will be placed over the center of the left ear lobe. The cathode will be placed over the antitragus. This method and these stimulation parameters have been previously used for reliable blinding in other clinical studies. Series of electrical pulses with 250 μs pulse width, 25 Hz frequency, and 28 s inter-burst interval (32 sec on/28 sec off duty cycle) will be applied in each intervention session. Auricular tVNS will be applied at 1mA - 5mA intensity for 30 min per session (1 session per day, 7 consecutive days a week, 14 sessions in total)

Also known as: NEMOS L tVNS device from the Neuraxon company

active tVNS group; sham tVNS group

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women between 18-79 years old
• Women diagnosed with Fibromyalgia according to the ACR 2016 Revised Classification Criteria
• Moderate to high pain intensity according to analog pain scales (above 4 points over 10), for more than 6 months
• Cognitive function sufficient to understand the experiments and follow instructions
• Ability to read and understand all information on the device display.
• Ability to adjust the strength of the stimulation or give feedback regarding their response to the device (feeling tingling/pulsating/pain).
• Ability to comply with the recommended therapy regiment of 30 min per day.
• The ear electrode needs to fit the patient.
• Patients with physical or mental disabilities
• The patient must be able to use the device by themselves or
• The patients' caretaker can operate the device on the patient. In this case the patient --must still be able to give feedback regarding their response to the device

You may not qualify if:

• Cardiac arrhythmias
• Pregnancy
• Serious mental disorder (dipolar disorder, schizophrenia etc.)
• Prior injury to the vagus nerve
• Individuals with scar tissue that may interfere with the stimulation
• Presence of an electrically or magnetically activated implant

Sponsors & Collaborators

• National and Kapodistrian University of Athens: lead

Study Sites (1)

Aretaieion University Hospital

Athens, Greece, 11523, Greece

RECRUITING

MeSH Terms

Conditions

Fibromyalgia; Pain; Depression; Sleep Wake Disorders; Fatigue

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization and Blinding Subjects that meet the inclusion criteria will be randomized to either the active (group 1) or the sham tVNS group (group 2). The assignment will be predetermined by a randomized assignment list, created prior to the enrollment of the first subject by an investigator from the Pain Clinic team who is not directly involved in subject treatment. The list will be created with randomization.org. There will be concealed allocation of treatment assignment such that investigators involved in subject screening, consent, and clinical scoring will be blinded to treatment condition. The subjects will be informed that they have a 50-50 chance of receiving either active or sham stimulation. Additionally, the assigned clinical evaluators will remain blinded to the stimulation condition. A medical provider not involved in the study will make the allocation of each patient according to the number.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assisitant Professor Of Anaesthesiology

Model Details: A double blind, sham-controlled randomized clinical trial * 1st group: Standard pharmacological Treatment according to EULAR + active tVNS, 30min/session, 7 days/week for 2 weeks (14 sessions total) * 2nd group: Standard pharmacological Treatment according to EULAR + sham tVNS, 30min/session, 7 days/week for 2 weeks (14 sessions total) * Regarding the standard pharmacological treatment we will follow a stepwise approach according to the EULAR (European League Against Rheumatism) recommendations.

Study Record Dates

• First Submitted: March 6, 2025
• First Posted: April 4, 2025
• Study Start: October 15, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-03

Locations

GR (1)