Vagus Nerve Stimulation for Fibromyalgia

Overseen By Jianren Mao, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Cardiac arrhythmia, Major psychiatric disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Fibromyalgia (FM) is a syndrome with clinical symptoms involving multiple systems. The efficacy of current treatments is inadequate, and more alternative modalities are needed for the management of FM patients. The parasympathetic vagus nerve innervates and integrates sensory, motor, and autonomic systems and has been suggested to play a role in pain modulation. The role of vagus nerve stimulation (VNS) as a treatment option for FM patients is yet to be investigated. The investigators propose to examine the hypothesis that vagus nerve stimulation could improve pain and related comorbid symptoms for FM patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Vagus Nerve Stimulation for fibromyalgia?

Research suggests that Vagus Nerve Stimulation (VNS) can help reduce chronic pain, including fibromyalgia, by affecting brain regions involved in pain processing and reducing inflammation. Studies have shown that both invasive and non-invasive VNS methods, like transcutaneous stimulation, are being explored for their potential to manage chronic pain effectively. ^{1 2 3 4 5}

Is vagus nerve stimulation safe for humans?

Vagus nerve stimulation (VNS), including non-invasive methods like transcutaneous VNS (tVNS), is generally considered safe for humans. While surgically implanted VNS can have serious side effects like infection and voice changes, non-invasive VNS has fewer risks, with mild effects such as ear pain and headache. Studies show no significant difference in adverse events between active tVNS and control groups, making it a safe option for clinical use. ^{1 3 6 7 8}

How does transcutaneous vagus nerve stimulation (tVNS) differ from other treatments for fibromyalgia?

Transcutaneous vagus nerve stimulation (tVNS) is unique because it is a non-invasive treatment that targets the vagus nerve to help reduce pain and improve symptoms in fibromyalgia by normalizing the body's stress response and immune functions, unlike traditional medications that primarily focus on pain relief. ^{1 9 10 11 12}

Eligibility Criteria

This trial is for individuals aged 18 to 70 who have been diagnosed with Fibromyalgia (FM) for at least three months and are experiencing a pain score of 4 or higher. It's open to both men and women.

Inclusion Criteria

I have been diagnosed with fibromyalgia for at least three months.

My pain level is 4 or higher on a scale of 0 to 10.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcutaneous Vagus Nerve Stimulation (tVNS) or sham point stimulation for 30 minutes per session, twice a day for 4 weeks

4 weeks

Daily sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 4 and 8 weeks

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Transcutaneous Vagus Nerve Stimulation

Trial Overview The study is testing Transcutaneous Vagus Nerve Stimulation (VNS) as a potential treatment for FM, aiming to see if it can improve pain and related symptoms by stimulating the vagus nerve non-invasively.

Participant Groups

Group I: Transcutaneous Vagus Nerve Stimulation(tVNS) Experimental Treatment 1 Intervention

receive tVNS 30 minutes per session, twice/day for 4 weeks and maintain regular medication treatment without change.

Group II: Sham Control group Active Control 1 Intervention

receive sham point stimulation 30 minutes per session, twice/day for 4 weeks and maintain regular medication treatment without change.

Transcutaneous Vagus Nerve Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as Vagus Nerve Stimulation for:

• Epilepsy
• Depression

Approved in European Union as Vagus Nerve Stimulation for:

• Epilepsy
• Depression

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Findings from Research

In a Phase I/II trial involving 14 patients with treatment-resistant fibromyalgia, vagus nerve stimulation (VNS) was found to be generally safe and tolerable, with side effects similar to those seen in epilepsy and depression treatments, including dry mouth and fatigue.

After 3 months of VNS, 5 out of 12 patients showed significant improvement in pain and overall wellness, with some patients even losing their fibromyalgia diagnosis criteria, suggesting VNS could be a promising adjunct treatment for fibromyalgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. Lange, G., Janal, MN., Maniker, A., et al.[2021]

Transcutaneous vagus nerve stimulation (TVNS) significantly reduced perceived pain intensity during heat stimulation compared to no intervention, with a notable hypoalgesic effect especially in men before the onset of temporal summation of pain (TSP).

In women, TVNS also decreased the TSP response compared to no intervention, but overall, the effects of TVNS were comparable to those of placebo and sham stimulation, indicating that while TVNS shows promise, its efficacy may vary by gender.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Electrical Transcutaneous Vagus Nerve Stimulation on the Perceived Intensity of Repetitive Painful Heat Stimuli: A Blinded Placebo- and Sham-Controlled Randomized Crossover Investigation. Janner, H., Klausenitz, C., Gürtler, N., et al.[2019]

Transcutaneous vagus nerve stimulation (tVNS) was found to significantly increase salivary alpha amylase (SAA) levels and reduce the decline of salivary cortisol in healthy participants, indicating a modulation of hormonal indices related to noradrenergic function.

However, tVNS did not show any significant effects on psychophysiological measures such as P3 amplitude or pupil size, suggesting that while it may influence hormonal responses, it does not impact certain cognitive or physiological indices in the same way.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential. Warren, CM., Tona, KD., Ouwerkerk, L., et al.[2019]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Vagus nerve stimulation (VNS) has shown promise in providing pain relief, in addition to its established benefits for conditions like epilepsy and depression, by modulating neural activity and reducing inflammation.

Both invasive and noninvasive VNS devices are being tested in clinical trials for chronic pain management, including conditions like fibromyalgia and headaches, highlighting its potential as a new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of vagus nerve stimulation in the treatment of chronic pain. Shao, P., Li, H., Jiang, J., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Transcutaneous vagus nerve stimulation (tVNS) shows promise for treating various conditions in pediatric patients, but current studies lack specific protocols and justification for its use in this age group, as none of the 15 identified studies focused exclusively on children.

There are no dedicated tVNS devices for pediatric use, and existing studies do not adequately address neurodevelopmental considerations, highlighting the need for more research on age-appropriate stimulation parameters and protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. Sigrist, C., Torki, B., Bolz, LO., et al.[2023]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

The study proposes a randomized, sham-controlled trial involving 136 fibromyalgia patients to evaluate the effects of non-invasive transcutaneous vagus nerve stimulation (tVNS) on pain intensity and quality of life, aiming to normalize altered autonomic and immune responses.

The researchers hypothesize that multiple sessions of tVNS (five times a week for four weeks) will significantly reduce pain intensity and improve overall health-related quality of life by enhancing vagal control over pain and immune functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Invasive Transcutaneous Vagus Nerve Stimulation for the Treatment of Fibromyalgia Symptoms: A Study Protocol. Molero-Chamizo, A., Nitsche, MA., Bolz, A., et al.[2022]

Transcutaneous cervical vagus nerve stimulation (tcVNS) significantly increased motor cortex excitability in healthy adults, as evidenced by a notable increase in motor-evoked potential (MEP) amplitude after real stimulation compared to sham stimulation.

The study involved 28 healthy participants and demonstrated that real tcVNS not only increased MEP amplitude but also decreased MEP latency, indicating a faster response time in the motor cortex, while no significant changes were observed in the resting motor threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous cervical vagus nerve stimulation improved motor cortex excitability in healthy adults: a randomized, single-blind, self-crossover design study. Wang, MX., Wumiti, A., Zhang, YW., et al.[2023]

Transcutaneous vagus nerve stimulation (t-VNS) significantly increased cardiac vagal tone by 22% and reduced heart rate by 4 beats per minute in 15 treatment-naïve patients with polymyalgia rheumatica (PMR) over a 5-day treatment period.

Patients reported a 14% reduction in pain for their hips after 5 days of t-VNS, indicating potential short-term benefits for managing PMR symptoms, although no long-term effects or changes in inflammatory markers were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Transcutaneous Vagus Nerve Stimulation in Patients with Polymyalgia Rheumatica. Venborg, J., Wegeberg, AM., Kristensen, S., et al.[2021]

Fibromyalgia (FM) is linked to dysfunction in neurotransmitter systems and low vagal tone, which may contribute to symptoms like chronic pain and fatigue, suggesting a biological basis for the condition.

The vagus nerve (VN) has anti-inflammatory properties and is associated with emotional regulation, indicating that targeting VN function could offer new therapeutic strategies for managing FM symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of the vagus nerve in fibromyalgia syndrome. Martins, DF., Viseux, FJF., Salm, DC., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Effects of Electrical Transcutaneous Vagus Nerve Stimulation on the Perceived Intensity of Repetitive Painful Heat Stimuli: A Blinded Placebo- and Sham-Controlled Randomized Crossover Investigation. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Role of vagus nerve stimulation in the treatment of chronic pain. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Non-Invasive Transcutaneous Vagus Nerve Stimulation for the Treatment of Fibromyalgia Symptoms: A Study Protocol. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous cervical vagus nerve stimulation improved motor cortex excitability in healthy adults: a randomized, single-blind, self-crossover design study. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The Effect of Transcutaneous Vagus Nerve Stimulation in Patients with Polymyalgia Rheumatica. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

The role of the vagus nerve in fibromyalgia syndrome. [2022]