Vagus Nerve Stimulation for Fibromyalgia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Massachusetts General Hospital
Disqualifiers: Cardiac arrhythmia, Major psychiatric disorder, others
No Placebo Group
Approved in 2 Jurisdictions
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.12345
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.13678
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.19101112
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.
I am between 18 and 70 years old.
Trial 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 (Device)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Active Control
Group I: Transcutaneous Vagus Nerve Stimulation(tVNS)Experimental Treatment1 Intervention
receive tVNS 30 minutes per session, twice/day for 4 weeks and maintain regular medication treatment without change.
Group II: Sham Control groupActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
References
Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. [2021]We performed an open-label Phase I/II trial to evaluate the safety and tolerability of vagus nerve stimulation (VNS) in patients with treatment-resistant fibromyalgia (FM) as well as to determine preliminary measures of efficacy in these patients.
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]Transcutaneous vagus nerve stimulation (TVNS) is a promising treatment for acute and chronic pain. However, experimental studies yielded controversial results. We examined if TVNS reduces the perceived intensity of repetitive painful heat stimulation and temporal summation of pain (TSP) in healthy volunteers in comparison with placebo and sham stimulation, as well as no intervention.
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]Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited.
Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]Non-invasive vagus nerve stimulation (VNS) may be administered via a novel, emerging neuromodulatory technique known as transcutaneous auricular vagus nerve stimulation (taVNS). Unlike cervically-implanted VNS, taVNS is an inexpensive and non-surgical method used to modulate the vagus system. taVNS is appealing as it allows for rapid translation of basic VNS research and serves as a safe, inexpensive, and portable neurostimulation system for the future treatment of central and peripheral disease. The background and rationale for taVNS is described, along with electrical and parametric considerations, proper ear targeting and attachment of stimulation electrodes, individual dosing via determination of perception threshold (PT), and safe administration of taVNS.
Role of vagus nerve stimulation in the treatment of chronic pain. [2023]Vagus nerve stimulation (VNS) can modulate vagal activity and neuro-immune communication. Human and animal studies have provided growing evidence that VNS can produce analgesic effects in addition to alleviating refractory epilepsy and depression. The vagus nerve (VN) projects to many brain regions related to pain processing, which can be affected by VNS. In addition to neural regulation, the anti-inflammatory property of VNS may also contribute to its pain-inhibitory effects. To date, both invasive and non-invasive VNS devices have been developed, with non-invasive devices including transcutaneous stimulation of auricular VN or carotid VN that are undergoing many clinical trials for chronic pain treatment. This review aims to provide an update on both preclinical and clinical studies of VNS in the management for chronic pain, including fibromyalgia, abdominal pain, and headaches, etc. We further discuss potential underlying mechanisms for VNS to inhibit chronic pain.
Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.
Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. [2023]Noninvasive transcutaneous vagus nerve stimulation (tVNS) has promising therapeutic potential in a wide range of applications across somatic and psychiatric conditions. Compared with invasive vagus nerve stimulation, good safety and tolerability profiles also support the use of tVNS in pediatric patients. Potential neurodevelopment-specific needs, however, raise concerns regarding the age-appropriate adjustment of treatment protocols and applied stimulation parameters.
Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on-off stimulation. Infection is the most serious implantation-associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6 months and depends on surgical skill and experience. The most frequent stimulation-associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non-invasive VNS delivery systems do not require surgery and permit patient-administered stimulation on demand. These non-invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.
Non-Invasive Transcutaneous Vagus Nerve Stimulation for the Treatment of Fibromyalgia Symptoms: A Study Protocol. [2022]Stimulation of the vagus nerve, a parasympathetic nerve that controls the neuro-digestive, vascular, and immune systems, induces pain relief, particularly in clinical conditions such as headache and rheumatoid arthritis. Transmission through vagal afferents towards the nucleus of the solitary tract (NST), the central relay nucleus of the vagus nerve, has been proposed as the main physiological mechanism that reduces pain intensity after vagal stimulation. Chronic pain symptoms of fibromyalgia patients might benefit from stimulation of the vagus nerve via normalization of altered autonomic and immune systems causing their respective symptoms. However, multi-session non-invasive vagal stimulation effects on fibromyalgia have not been evaluated in randomized clinical trials. We propose a parallel group, sham-controlled, randomized study to modulate the sympathetic-vagal balance and pain intensity in fibromyalgia patients by application of non-invasive transcutaneous vagus nerve stimulation (tVNS) over the vagal auricular and cervical branches. We will recruit 136 fibromyalgia patients with chronic moderate to high pain intensity. The primary outcome measure will be pain intensity, and secondary measures will be fatigue, health-related quality of life, sleep disorders, and depression. Heart rate variability and pro-inflammatory cytokine levels will be obtained as secondary physiological measures. We hypothesize that multiple tVNS sessions (five per week, for 4 weeks) will reduce pain intensity and improve quality of life as a result of normalization of the vagal control of nociception and immune-autonomic functions. Since both vagal branches project to the NST, we do not predict significantly different results between the two stimulation protocols.
Transcutaneous cervical vagus nerve stimulation improved motor cortex excitability in healthy adults: a randomized, single-blind, self-crossover design study. [2023]To investigate the effect of transcutaneous cervical vagus nerve stimulation (tcVNS) on motor cortex excitability in healthy adults.
The Effect of Transcutaneous Vagus Nerve Stimulation in Patients with Polymyalgia Rheumatica. [2021](1) Polymyalgia rheumatica (PMR) is an inflammatory disease characterised by pain, morning stiffness, and reduced quality of life. Recently, vagus nerve stimulation (VNS) was shown to have anti-inflammatory effects. We aimed to examine the effect of transcutaneous VNS (t-VNS) on PMR. (2) Fifteen treatment-naïve PMR patients completed the study. Patients underwent a 5-day protocol, receiving 2 min of t-VNS stimulation bilaterally on the neck, three times daily. Cardiac vagal tone (CVT) measured on a linear vagal scale (LVS), blood pressure, heart rate, patient-reported outcome, and biochemical changes were assessed. (3) t-VNS induced a 22% increase in CVT at 20 min after initial stimulations compared with baseline (3.4 ± 2.2 LVS vs. 4.1 ± 2.9 LVS, p = 0.02) and was accompanied by a 4 BPM reduction in heart rate (73 ± 11 BPM vs. 69 ± 9, p < 0.01). No long-term effects were observed. Furthermore, t-VNS induced a 14% reduction in the VAS score for the hips at day 5 compared with the baseline (5.1 ± 2.8 vs. 4.4 ± 2.8, p = 0.04). No changes in CRP or proinflammatory analytes were observed. (4) t-VNS modulates the autonomic nervous system in patients with PMR, but further investigation of t-VNS in PMR patients is warranted.
The role of the vagus nerve in fibromyalgia syndrome. [2022]Fibromyalgia (FM) syndrome is a common illness characterized by chronic widespread pain, sleep problems, fatigue, and cognitive difficulties. Dysfunctional neurotransmitter systems that influence the body's endogenous stress response systems are thought to underlie many of the major FM-related symptoms. A model of FM pathogenesis suggests biological and psychosocial variables interact to influence the genetic predisposition, but the precise mechanisms remain unclear. The Polyvagal Theory provides a theoretical framework from which to investigate potential biological mechanisms. The vagus nerve (VN) has anti-inflammatory properties via its afferent and efferent fibers. A low vagal tone (as assessed by low heart rate variability), has been observed in painful and inflammatory diseases, including FM, while the ventral branch of the VN is linked to emotional expression and social engagement. These anti-inflammatory and psychological (limbic system) properties of the VN may possess therapeutic potential in treating FM. This review paper summarizes the scientific literature regarding the potential role of the VN in transducing and/or therapeutically managing FM signs and symptoms.