scholarly journals Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study Protocol

2021 ◽  
Vol 15 ◽  
Author(s):  
Eric Azabou ◽  
Guillaume Bao ◽  
Félicie Costantino ◽  
Madalina Jacota ◽  
Chanez Lazizi ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Axial Spondyloarthritis ◽  
Vagal Nerve ◽  
Control Group ◽  
Attractive Alternative ◽  
Anatomical Site ◽  
Double Blind ◽  
Non Invasive ◽  
Asas Classification Criteria

Axial spondyloarthritis (SpA), is a major cause of chronic pain and disability that profoundly alters the quality of life of patients. Nearly half of patients with SpA usually develop drug resistance. Non-pharmacological treatments targeting inflammation are an attractive alternative to drug administration. Vagus nerve stimulation (VNS), by promoting a cholinergic anti-inflammatory reflex holds promise for treating inflammatory disease. Inflammatory reflex signaling, which is enhanced by electrically stimulating the vagus nerve, significantly reduces cytokine production and attenuates disease severity in animal models of endotoxemia, sepsis, colitis, and other preclinical models of inflammatory diseases. It has been proposed that vagal efferent fibers release acetylcholine (Ach), which can interact with α7-subunit-containing nicotinic receptors expressed by tissue macrophages and other immune cells to rapidly inhibit the synthesis/release of pro-inflammatory cytokines such as TNFα, IL-1β, IL-6, and IL-18. External vagal nerve stimulation devices are now available that do not require surgery nor implantation to non-invasively stimulate the vagal nerve. This double-blind randomized cross-over clinical trial aims to study the change in SpA disease activity, according to Assessment in Ankylosing Spondylitis 20 (ASAS20) definition, after 12 weeks of non-invasive VNS treatment vs. non-specific dummy stimulation (control group). One hundred and twenty adult patients with drug resistant SpA, meeting the ASAS classification criteria, will be included in the study. Patients will be randomized into two parallel groups according to a cross over design: either active VNS for 12 weeks, then dummy stimulation for 12 weeks, or dummy stimulation for 12 weeks, then active VNS for 12 weeks. The two stimulation periods will be separated by a 4 weeks wash-out period. A transcutaneous auricular vagus nerve stimulator Tens Eco Plus SCHWA MEDICOTM France will be used in this study. The active VNS stimulation will be applied in the cymba conchae of the left ear upon the auricular branch of the vagus nerve, using low intensity (2–5 mA), once à week, during 1 h. Dummy stimulation will be performed under the same conditions and parameters as active VNS stimulation, but at an irrelevant anatomical site: the left ear lobule. This multicenter study was registered on ClinicalTrials.gov: NCT04286373.

scholarly journals Non–Invasive Vagus Nerve Stimulation for the ACute Treatment of Cluster Headache: Findings From the Randomized, Double‐Blind, Sham‐Controlled ACT1 Study

2016 ◽  
Vol 56 (8) ◽  
pp. 1317-1332 ◽  
Author(s):  
Stephen D. Silberstein ◽  
Laszlo L. Mechtler ◽  
David B. Kudrow ◽  
Anne H. Calhoun ◽  
Candace McClure ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Acute Treatment ◽  
Double Blind ◽  
Non Invasive

scholarly journals Auricular Neuromodulation for Mass Vagus Nerve Stimulation: Insights From SOS COVID-19 a Multicentric, Randomized, Controlled, Double-Blind French Pilot Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Claire-Marie Rangon ◽  
Régine Barruet ◽  
Abdelmadjid Mazouni ◽  
Chloé Le Cossec ◽  
Sophie Thevenin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Vagus Nerve ◽  
Clinical Outcomes ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Treated Patient ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Non Invasive ◽  
The Impact

Importance: An exacerbated inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is believed to be one of the major causes of the morbidity and mortality of the coronavirus disease 2019 (COVID-19). Neuromodulation therapy, based on vagus nerve stimulation, was recently hypothesized to control both the SARS-CoV-2 replication and the ensuing inflammation likely through the inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway and could improve the clinical outcomes as an adjunct treatment. We proposed to test it by the stimulation of the auricular branch of the vagus nerve, i.e., auricular neuromodulation (AN), a non-invasive procedure through the insertion of semipermanent needles on the ears.Objective: The aim of this study was to assess the effect of AN on the clinical outcomes in patients affected by COVID-19.Design, Setting, and Participants: A multicenter, randomized, placebo-controlled, double-blind clinical trial included 31 patients with respiratory failure due to COVID-19 requiring hospitalization. Within 72 h after admission, patients received either AN (n = 14) or sham neuromodulation (SN, n = 15) in addition to the conventional treatments.Main Outcome and Measures: The primary endpoint of the study was the rate of a clinical benefit conferred by AN at Day 14 (D14) as assessed by a 7-point Clinical Progression Scale. The secondary endpoint of the study was the impact of AN on the rate of transfer to the intensive care unit (ICU) and on the survival rate at D14.Results: The AN procedure was well-tolerated without any reported side effects but with no significant improvement for the measures of both primary (p > 0.3) and secondary (p > 0.05) endpoints at the interim analysis. None of the AN-treated patients died but one in the SN group did (81 years). Two AN-treated patients (73 and 79 years, respectively) and one SN-treated patient (59 years) were transferred to ICU. Remarkably, AN-treated patients were older with more representation by males than in the SN arm (i.e., the median age of 75 vs. 65 years, 79% male vs. 47%).Conclusion: The AN procedure, which was used within 72 h after the admission of patients with COVID-19, was safe and could be successfully implemented during the first two waves of COVID-19 in France. Nevertheless, AN did not significantly improve the outcome of the patients in our small preliminary study. It is pertinent to explore further to validate AN as the non-invasive mass vagal stimulation solution for the forthcoming pandemics.Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT04341415].

scholarly journals Rationale and design for a randomized, single-center, double-blind, sham-controlled study of non-invasive vagus nerve stimulation for treatment of post-traumatic headache

Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S1.1-S1
Author(s):  
Bert Vargas ◽  
Eric Liebler ◽  
Stephen Bunt ◽  
Charlene Supent-Bell
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Acute Treatment ◽  
Preventive Therapy ◽  
Efficacy And Safety ◽  
Headache Disorders ◽  
Double Blind ◽  
Non Invasive ◽  
Post Traumatic

ObjectiveEvaluate the efficacy and safety of non-invasive vagus nerve stimulation (nVNS) for the treatment of post-traumatic headache (PTH).BackgroundWorldwide, ∼69 million people per year sustain a traumatic brain injury (TBI), many of whom develop PTH. Clinicians often treat PTH with drugs approved for primary headache disorders, and many patients self-treat with over-the-counter agents but have inadequate pain relief. There has been little study of therapies for PTH, and safe, effective treatments are needed.Design/MethodsThis randomized, double-blind, sham-controlled, parallel-group pilot study is enrolling adults who present 1–4 weeks after a head injury, meet International Classification of Headache Disorders 3rd edition (ICHD-3) criteria for acute headache attributed to mild TBI, and have ≥2 headaches/week with a migraine or probable migraine phenotype. After a 2-week run-in period, subjects are randomly assigned (1:1 allocation) to receive daily preventive therapy and as-needed acute treatment with nVNS or a sham device. Preventive therapy consists of two 120-second stimulations 3 times daily. Acute treatment comprises 2 stimulations at headache onset and 2 stimulations 20 minutes after the start of initial treatment. Subjects are not to use acute rescue medication for 120 minutes post-treatment. One North American site will enroll ≤80 subjects. The expected duration is 12 months (enrollment, 9 months; participation, 14 weeks).ResultsThe primary effectiveness end point is decrease in pain (on a 7-point scale) 60 minutes post-treatment for all treated headache attacks. Secondary end points include decrease in the frequency of headache days between the run-in period and the last 2 weeks of the double-blind period and responder rates (ie, percentages of subjects with ≥50% decrease in attack frequency). The primary safety end point is the incidence of treatment-related serious adverse events.ConclusionsThis study will assess the efficacy and safety of nVNS as a novel therapy for PTH.

Non-invasive vagus nerve stimulation for prevention of migraine: The multicenter, randomized, double-blind, sham-controlled PREMIUM II trial

Cephalalgia ◽  
2022 ◽  
pp. 033310242110688
Author(s):  
Umer Najib ◽  
Timothy Smith ◽  
Nada Hindiyeh ◽  
Joel Saper ◽  
Barbara Nye ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Sham Group ◽  
Active Group ◽  
Tolerability Profile ◽  
Migraine Prevention ◽  
Double Blind ◽  
Intention To Treat ◽  
Non Invasive

Aim Evaluate the efficacy and safety of non-invasive vagus nerve stimulation for migraine prevention. Methods After completing a 4-week diary run-in period, adults who had migraine with or without aura were randomly assigned to receive active non-invasive vagus nerve stimulation or sham therapy during a 12-week double-blind period. Results Of 336 enrolled participants, 113 (active, n = 56; sham, n = 57) completed ≥70 days of the double-blind period and were ≥66% adherent with treatment, comprising the prespecified modified intention-to-treat population. The COVID-19 pandemic led to early trial termination, and the population was ∼60% smaller than the statistical target for full power. Mean reduction in monthly migraine days (primary endpoint) was 3.12 for the active group and 2.29 days for the sham group (difference, −0.83; p = 0.2329). Responder rate (i.e. the percentage of participants with a ≥50% reduction in migraine days) was greater in the active group (44.87%) than the sham group (26.81%; p = 0.0481). Prespecified subgroup analysis suggested that participants with aura responded preferentially. No serious device-related adverse events were reported. Conclusions These results suggest clinical utility of non-invasive vagus nerve stimulation for migraine prevention, particularly for patients who have migraine with aura, and reinforce the well-established safety and tolerability profile of this therapy. Trial Registration: ClinicalTrials.gov (NCT03716505).

scholarly journals Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A randomized, double-blind, sham-controlled ACT2 study

Cephalalgia ◽  
2017 ◽  
Vol 38 (5) ◽  
pp. 959-969 ◽  
Author(s):  
Peter J Goadsby ◽  
Ilse F de Coo ◽  
Nicholas Silver ◽  
Alok Tyagi ◽  
Fayyaz Ahmed ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Acute Treatment ◽  
Chronic Cluster Headache ◽  
Double Blind ◽  
Non Invasive ◽  
Rescue Treatment ◽  
Full Analysis

Background Clinical observations and results from recent studies support the use of non-invasive vagus nerve stimulation (nVNS) for treating cluster headache (CH) attacks. This study compared nVNS with a sham device for acute treatment in patients with episodic or chronic CH (eCH, cCH). Methods After completing a 1-week run-in period, subjects were randomly assigned (1:1) to receive nVNS or sham therapy during a 2-week double-blind period. The primary efficacy endpoint was the proportion of all treated attacks that achieved pain-free status within 15 minutes after treatment initiation, without rescue treatment. Results The Full Analysis Set comprised 48 nVNS-treated (14 eCH, 34 cCH) and 44 sham-treated (13 eCH, 31 cCH) subjects. For the primary endpoint, nVNS (14%) and sham (12%) treatments were not significantly different for the total cohort. In the eCH subgroup, nVNS (48%) was superior to sham (6%; p < 0.01). No significant differences between nVNS (5%) and sham (13%) were seen in the cCH subgroup. Conclusions Combing both eCH and cCH patients, nVNS was no different to sham. For the treatment of CH attacks, nVNS was superior to sham therapy in eCH but not in cCH. These results confirm and extend previous findings regarding the efficacy, safety, and tolerability of nVNS for the acute treatment of eCH.

scholarly journals Non-invasive vagus nerve stimulation improves clinical and molecular biomarkers of Parkinson’s disease in patients with freezing of gait

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Banashree Mondal ◽  
Supriyo Choudhury ◽  
Rebecca Banerjee ◽  
Akash Roy ◽  
Koustav Chatterjee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Vagus Nerve ◽  
Motor Function ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Freezing Of Gait ◽  
Double Blind ◽  
Non Invasive ◽  
Markers Of Inflammation

AbstractNon-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled crossover trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson’s disease (PD) patients. In a subgroup of patients, we measured selected neurotrophin levels and markers of inflammation and oxidative stress in serum, before and after the experimental intervention. Thirty-three PD patients with associated freezing of gait were randomised to either nVNS or sham. After baseline assessments, patients were instructed to deliver 6 two-minute stimulations (total 12 min/day) of the nVNS/sham device (electroCore, Inc. USA) for one month at home. Patients were then re-assessed. After a washout period of one month, the same patients were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters were observed with nVNS, including walking speed, stance time and step length, compared to sham. Similarly, overall motor function (MDS-UPDRS III) also improved significantly following nVNS stimulation. Serum Tumor Necrosis Factor (TNF)-α and glutathione levels decreased and brain-derived neurotrophic factor (BDNF) levels increased significantly (p < 0.05) after treatment with nVNS. Here we present the first double-blind sham-controlled trial evidence of the efficacy and safety of nVNS in the treatment of gait and motor function in patients with PD.

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