Vagus Nerve Stimulation for Multiple Sclerosis
Recruiting in Palo Alto (17 mi)
Overseen ByJeffrey Bennett, MD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Colorado, Denver
No Placebo Group
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?The goal of this clinical trial is to learn if stimulating the vagus nerve in combination with a motor task in people with multiple sclerosis can improve motor function. The main questions it aims to answer are:
* Is stimulating the vagus nerve safe and feasible after demyelinating episodes?
* Does a paired motor task with vagus nerve stimulation improve motor function with someone who has multiple sclerosis?
Researchers will compare active vagus nerve stimulation to a sham stimulation to see if the paired vagus nerve stimulation can improve motor control.
Participants will:
* Come in for study visits over a six month period. Study visits are three times weekly for the first month, then single follow up visits at two, three, and six months.
* During study visits, participants will complete 30 minutes of the paired vagus nerve stimulation with a motor task, specifically the grooved peg test.
* At various timepoints in the study, motor and disability tests will be administered to see if there are any changes in motor control for that participants. These tests include the timed 25 foot walk test, expanded disability scale, the upper extremity portion of the Fugl-Meyer Assessment, and the Multiple Sclerosis Impact Scale - 29.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you are allowed to continue or start disease-modifying therapy to help manage multiple sclerosis during the study.
What data supports the effectiveness of the treatment Closed Loop Trans-Auricular Vagus Nerve Stimulation System for Multiple Sclerosis?
Vagus nerve stimulation (VNS) has been shown to be effective in treating epilepsy and depression, and it is being explored for various inflammatory and systemic diseases due to its ability to modulate the immune system and reduce inflammation. This suggests potential benefits for conditions like Multiple Sclerosis, which involves immune system dysfunction.
12345Is vagus nerve stimulation safe for humans?
Vagus nerve stimulation (VNS) is generally considered safe, with most side effects being mild and temporary, such as voice changes, tingling, or ear pain. Serious issues are rare, especially with non-invasive methods, which avoid surgery and allow patients to control the stimulation themselves.
16789How does the Closed Loop Trans-Auricular Vagus Nerve Stimulation System treatment for Multiple Sclerosis differ from other treatments?
This treatment is unique because it uses a non-invasive method to stimulate the vagus nerve through the ear, and it operates in a closed-loop system that adjusts stimulation based on real-time physiological data, potentially offering a more personalized therapy compared to traditional methods.
1231011Eligibility Criteria
This trial is for individuals with Multiple Sclerosis who can attend study visits over six months. They will perform a motor task paired with vagus nerve stimulation to see if it improves their motor function.Inclusion Criteria
I have noticeable difficulty using my dominant hand or my disability score is 2.5 or higher.
Exclusion Criteria
I do not have any uncontrolled serious health issues.
I have a history of seizures or epilepsy.
I have a brain condition or have had significant brain injury.
I have previously received treatments like total body irradiation or specific medications for remyelination.
My condition is primary progressive multiple sclerosis.
I have an ear infection or abnormal ear shape.
I cannot walk 25 feet without stopping.
Participant Groups
The trial tests whether stimulating the vagus nerve while doing a movement task (like the grooved peg test) is safe and helps improve motor control in people with MS, compared to sham stimulation.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Experimental - Active StimulationExperimental Treatment1 Intervention
Participants in this arm will receive active stimulation during the paired motor task.
Group II: Control - Sham StimulationPlacebo Group1 Intervention
Participants in this arm will receive sham stimulation during the paired motor task to create a control to the experimental group.
Closed Loop Trans-Auricular Vagus Nerve Stimulation System is already approved in United States, European Union for the following indications:
๐บ๐ธ Approved in United States as Vagus Nerve Stimulation for:
- Epilepsy
๐ช๐บ 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:
Clinical Translational Research Center at CU AnschutzAurora, CO
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Who is running the clinical trial?
University of Colorado, DenverLead Sponsor
References
Vagus nerve stimulation: a proven therapy for treatment of epilepsy strives to improve efficacy and expand applications. [2020]Vagus nerve stimulation (VNS) is an approved therapy for the treatment of adult patients and adolescents aged 12 years and older who have partial onset seizures refractory to antiepileptic medications. More than 50,000 patients worldwide have been implanted with the VNS system. Work continues to understand the mechanism of action of VNS with the goal of improving the treatment, particularly to identify patients who will be helped by VNS, to develop a closed-loop seizure detection system, and to improve the selection of stimulation parameters. VNS has also been approved for treatment-resistant depression, and it may have utility in the treatment of a variety of other medical disorders.
Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers. [2021]Cervical vagus nerve stimulation (VNS) is an emerging bioelectronic treatment for brain, metabolic, cardiovascular and immune disorders. Its desired and off-target effects are mediated by different nerve fiber populations and knowledge of their engagement could guide calibration and monitoring of VNS therapies.
Neuroimmunomodulation of vagus nerve stimulation and the therapeutic implications. [2023]Vagus nerve stimulation (VNS) is a technology that provides electrical stimulation to the cervical vagus nerve and can be applied in the treatment of a wide variety of neuropsychiatric and systemic diseases. VNS exerts its effect by stimulating vagal afferent and efferent fibers, which project upward to the brainstem nuclei and the relayed circuits and downward to the internal organs to influence the autonomic, neuroendocrine, and neuroimmunology systems. The neuroimmunomodulation effect of VNS is mediated through the cholinergic anti-inflammatory pathway that regulates immune cells and decreases pro-inflammatory cytokines. Traditional and non-invasive VNS have Food and Drug Administration (FDA)-approved indications for patients with drug-refractory epilepsy, treatment-refractory major depressive disorders, and headaches. The number of clinical trials and translational studies that explore the therapeutic potentials and mechanisms of VNS is increasing. In this review, we first introduced the anatomical and physiological bases of the vagus nerve and the immunomodulating functions of VNS. We covered studies that investigated the mechanisms of VNS and its therapeutic implications for a spectrum of brain disorders and systemic diseases in the context of neuroimmunomodulation.
Transcutaneous auricular vagus nerve stimulation attenuates inflammatory bowel disease in children: a proof-of-concept clinical trial. [2023]Vagus nerve stimulation is an investigational anti-inflammatory therapy targeting the nervous system to modulate immune activity. This study evaluated the efficacy and safety of transcutaneous auricular VNS (ta-VNS) in patients with pediatric-onset Crohn's disease (CD) or ulcerative colitis (UC).
Vagus Nerve Stimulation in Rodent Models: An Overview of Technical Considerations. [2023]Over the last several decades, vagus nerve stimulation (VNS) has evolved from a treatment for select neuropsychiatric disorders to one that holds promise in treating numerous inflammatory conditions. Growing interest has focused on the use of VNS for other indications, such as heart failure, rheumatoid arthritis, inflammatory bowel disease, ischemic stroke, and traumatic brain injury. As pre-clinical research often guides expansion into new clinical avenues, animal models of VNS have also increased in recent years. To advance this promising treatment, however, there are a number of experimental parameters that must be considered when planning a study, such as physiology of the vagus nerve, electrical stimulation parameters, electrode design, stimulation equipment, and microsurgical technique. In this review, we discuss these important considerations and how a combination of clinically relevant stimulation parameters can be used to achieve beneficial therapeutic results in pre-clinical studies of sub-acute to chronic VNS, and provide a practical guide for performing this work in rodent models. Finally, by integrating clinical and pre-clinical research, we present indeterminate issues as opportunities for future research.
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.
Vagus nerve stimulation for refractory epilepsy: a transatlantic experience. [2019]Vagus nerve stimulation (VNS) is an alternative treatment for medically or surgically refractory epilepsy. The long-term efficacy and safety of VNS were evaluated in a large patient series at Ghent University Hospital and Dartmouth-Hitchcock Medical Center. Between March 1995 and February 2003, seizure frequency and type as well as prescribed antiepileptic drugs and side effects were prospectively assessed in 131 patients treated with VNS in either center. Patients with a minimum follow-up duration of 6 months were included in the efficacy and safety analysis. A total of 118 of 131 implanted patients had a minimum postimplantation follow-up period of 6 months (mean, 33 months). The mean age of these patients was 32 years and the mean duration of refractory epilepsy was 22 years. The mean reduction in monthly seizure frequency in all patients was 55% (range, 0-100; SD = 31.6). Seven percent of patients were free of seizures with impaired consciousness, 50% of patients had a seizure frequency reduction of more than 50%, and 21% of patients were nonresponders. Fifteen patients reported stimulation-related side effects such as hoarseness or gagging. In a large patient series from two geographically distinct epilepsy centers located in two different continents, VNS proved to be efficacious and safe during long-term follow-up.
Adverse events in children receiving intermittent left vagal nerve stimulation. [2019]The purpose of this study was to determine the frequency of unexpected events during intermittent vagal nerve stimulation in 24 patients stimulated for a total of 61 patient years. The charts of 24 children undergoing periodic stimulation of the left vagal nerve on research protocols were reviewed to determine the nature and frequency of adverse events and the total length of time they were stimulated. Fifteen adverse events were discovered in 12 patients. Thirteen were likely related to the device, and four other events might have been related. Two of these resulted in voluntary termination of vagal nerve stimulation, and the rest were treatable. Vagal nerve stimulation was tolerated in this series of patients. As opposed to the more standard drug therapies, adverse events during vagal nerve stimulation do not necessitate termination of therapy, but these events frequently lead to unforeseen surgery under general anesthesia.
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 vagus nerve stimulation - A brief introduction and overview. [2022]Invasive cervical vagus nerve stimulation (VNS) is approved for the treatment of epilepsies, depression, obesity, and for stroke-rehabilitation. The procedure requires surgery, has side-effects, is expensive and not readily available. Consequently, transcutaneous VNS (tVNS) has been developed 20 years ago as non-invasive, less expensive, and easily applicable alternative. Since the vagus nerve reaches the skin at the outer acoustic canal and ear, and reflex-responses such as the ear-cough-reflex or the auriculo-cardiac reflex have been observed upon auricular stimulation, the ear seems well suited for tVNS. However, several sensory nerves with variable fiber-density and significant overlap innervate the outer ear: the auricular branch of the vagus nerve (ABVN), the auriculotemporal nerve, greater auricular nerve, and to some extent the lesser occipital nerve. VNS requires activation of Aฮฒ-fibers which are far less present in the ABVN than the cervical vagus nerve. Thus, optimal stimulation sites and parameters, and tVNS-algorithms need to be further explored. Unravelling central pathways and structures that mediate tVNS-effects is another challenge. tVNS impulses reach the nucleus of the solitary tract and activate the locus-coeruleus-norepinephrine system. However, many more brain areas are activated or deactivated upon VNS, including structures of the central autonomic network and the limbic system. Still, the realm of therapeutic tVNS applications grows rapidly and includes medication-refractory epilepsies, depressive mood disorders, headaches including migraine, pain, heart failure, gastrointestinal inflammatory diseases and many more. tVNS might become a standard tool to enhance autonomic balance and function in various autonomic, neurological, psychiatric, rheumatologic, as well as other diseases.
Auricular vagus nerve stimulator for closed-loop biofeedback-based operation. [2022]Auricular vagus nerve stimulation (aVNS) is a novel neuromodulatory therapy used for treatment of various chronic systemic disorders. Currently, aVNS is non-individualized, disregarding the physiological state of the patient and therefore making it difficult to reach optimum therapeutic outcomes. A closed-loop aVNS system is required to avoid over-stimulation and under-stimulation of patients, leading to personalized and thus improved therapy. This can be achieved by continuous monitoring of individual physiological parameters that serve as a basis for the selection of optimal aVNS settings. In this work we developed a novel aVNS hardware for closed-loop application, which utilizes cardiorespiratory sensing using embedded sensors (and/or external sensors), processes and analyzes the acquired data in real-time, and directly governs settings of aVNS. We show in-lab that aVNS stimulation can be arbitrarily synchronized with respiratory and cardiac phases (as derived from respiration belt, electrocardiography and/or photo plethysmography) while mimicking baroreceptor-related afferent input along the vagus nerve projecting into the brain. Our designed system identified > 90% of all respiratory and cardiac cycles and activated stimulation at the target point with a precision of ยฑ 100 ms despite the intrinsic respiratory and heart rate variability reducing the predictability. The developed system offers a solid basis for future clinical research into closed-loop aVNS in favour of personalized therapy.