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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether stimulating the vagus nerve, a key nerve involved in pain control, can reduce pain in people with fibromyalgia. Participants will use either a device that stimulates the nerve (Transcutaneous Vagus Nerve Stimulation, or tVNS) or a placebo device to determine if there is a real benefit. The goal is to discover a new way to manage fibromyalgia pain and symptoms, which current treatments don't fully address. Individuals who have had fibromyalgia for at least three months and experience moderate to severe pain might be suitable for this study. As an unphased study, this trial offers a unique opportunity to explore innovative pain management solutions for fibromyalgia.

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 prior data suggests that this vagus nerve stimulation is safe for fibromyalgia patients?

Research has shown that transcutaneous vagus nerve stimulation (tVNS) is generally safe. Studies have found that tVNS is noninvasive, meaning it doesn't involve surgery or entering the body, and it has few side effects. People using tVNS for conditions like epilepsy and depression have reported side effects similar to those with standard vagus nerve stimulation (VNS), such as dry mouth and fatigue. However, these effects are usually mild. Overall, tVNS is well-tolerated and considered a promising new treatment option for fibromyalgia. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for fibromyalgia, which often involve medications like antidepressants, pain relievers, or anti-seizure drugs, transcutaneous Vagus Nerve Stimulation (tVNS) offers a non-invasive approach by directly targeting the nervous system. This technique uses electrical impulses to stimulate the vagus nerve through the skin, potentially helping to modulate pain and improve symptoms without the side effects typical of many medications. Researchers are excited about tVNS because it represents a novel mechanism of action, tapping into the body's own nerve pathways to manage fibromyalgia, which could lead to more personalized and effective treatments.

What evidence suggests that vagus nerve stimulation is effective for fibromyalgia?

Research has shown that stimulating the vagus nerve (VNS) might help reduce chronic pain associated with fibromyalgia. Studies have found that VNS can address issues in the body's autonomic nervous system and immune system, which are often present in fibromyalgia. In this trial, participants will receive either transcutaneous VNS (tVNS) or a sham control. The non-invasive method, tVNS, might interrupt the cycles that exacerbate pain and negative emotions in fibromyalgia patients. Some research suggests that tVNS can lower pain levels in individuals with chronic pain. These findings indicate that tVNS could be a promising new way to manage fibromyalgia symptoms. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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]

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 (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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06912334

Transcutaneous Vagus Nerve Stimulation on Fibromyalgia- ... The chronic pain symptoms of fibromyalgia patients may benefit from vagus nerve stimulation, by normalizing the autonomic and immune system dysfunction that ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10914987/

Evaluating the efficacy and acceptability of vagus nerve ... Recently, vagus nerve stimulation (VNS) has emerged as a promising therapy for fibromyalgia. Nonetheless, despite the increasing number of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1297319X25001289

Non-invasive auricular vagus nerve stimulation in ... If effective, tVNS may help to disrupt the pathological feedback loops that sustain heightened pain sensitivity and maladaptive cognitive-emotional responses, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11309651/

Transcutaneous vagus nerve stimulation effects on chronic pain The results of our analyses indicate that tVNS could be an effective intervention for managing pain intensity in chronic pain conditions. In the ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06912334/transcutaneous-vagus-nerve-stimulation-on-fibromyalgia-double-blind-sham-controlled-randomized-clinical-trial

Transcutaneous Vagus Nerve Stimulation on Fibromyalgia The chronic pain symptoms of fibromyalgia patients may benefit from vagus nerve stimulation, by normalizing the autonomic and immune system ...

6. academic.oup.com academic.oup.com/painmedicine/article/12/9/1406/1899449

Safety and Efficacy of Vagus Nerve Stimulation in Fibromyalgia Results. Side effects were similar to those reported in patients treated with VNS for epilepsy or depression and, in addition, dry mouth and fatigue were ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1110116423000157

Pain neuroscience education versus transcutaneous vagal ... To evaluate the effectiveness of pain neuroscience education (PNE) and transcutaneous vagal nerve stimulation (tVNS) for fibromyalgia (FM) patients.