Publications by authors named "Eric Liebler"

29 Publications

  • Page 1 of 1

NOn-invasive Vagus nerve stimulation in acute Ischemic Stroke (NOVIS): a study protocol for a randomized clinical trial.

Trials 2020 Oct 26;21(1):878. Epub 2020 Oct 26.

Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.

Background: Secondary damage due to neurochemical and inflammatory changes in the penumbra in the first days after ischemic stroke contributes substantially to poor clinical outcome. In animal models, vagus nerve stimulation (VNS) inhibits these detrimental changes and thereby reduces tissue injury. The aim of this study is to investigate whether non-invasive cervical VNS (nVNS) in addition to the current standard treatment can improve penumbral recovery and limit final infarct volume.

Methods: NOVIS is a single-center prospective randomized clinical trial with blinded outcome assessment. One hundred fifty patients will be randomly allocated (1:1) within 12 h from clinical stroke onset to nVNS for 5 days in addition to standard treatment versus standard treatment alone. The primary endpoint is the final infarct volume on day 5 assessed with MRI.

Discussion: We hypothesize that nVNS will result in smaller final infarct volumes as compared to standard treatment due to improved penumbral recovery. The results of this study will be used to assess the viability and approach to power a larger trial to more definitively assess the clinical efficacy of nVNS after stroke.

Trial Registration: ClinicalTrials.gov NCT04050501 . Registered on 8 August 2019.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-020-04794-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586413PMC
October 2020

Non-invasive vagus nerve stimulation for primary headache: A clinical update.

Cephalalgia 2020 10 27;40(12):1370-1384. Epub 2020 Jul 27.

Institute for Medical Informatics, Biometry and Epidemiology, Medical Faculty of the University of Duisburg-Essen, Essen, Germany.

Background: Non-invasive vagus nerve stimulation (nVNS) is a proven treatment for cluster headache and migraine. Several possible mechanisms of action by which nVNS mitigates headache have been identified.

Methods: We conducted a narrative review of recent scientific and clinical research into nVNS for headache, including findings from mechanistic studies and their possible relationships to the clinical effects of nVNS.

Results: Findings from animal and human studies have provided possible mechanistic explanations for nVNS efficacy in headache involving four core areas: Autonomic nervous system functions; cortical spreading depression inhibition; neurotransmitter regulation; and nociceptive modulation. We discuss how overlap and interplay among these areas may underlie the utility of nVNS in the context of clinical evidence supporting its safety and efficacy as acute and preventive therapy for both cluster headache and migraine. Possible future nVNS applications are also discussed.

Conclusion: Significant progress over the past several years has yielded valuable mechanistic and clinical evidence that, combined with the excellent safety and tolerability profile of nVNS, suggests that it should be considered a first-line treatment for both acute and preventive treatment of cluster headache, an effective option for acute treatment of migraine, and a highly relevant, practical option for migraine prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0333102420941864DOI Listing
October 2020

A Randomized Sham-Controlled Cross-Over Study on the Short-Term Effect of Non-Invasive Cervical Vagus Nerve Stimulation on Spinal and Supraspinal Nociception in Healthy Subjects.

Headache 2020 Sep 27;60(8):1616-1631. Epub 2020 Jun 27.

Department of Neurology, University of Munich, Munich, Germany.

Objective: The aim of the present study was to test the effects of vagus nerve stimulation (VNS) on the descending pain inhibition, quantified by the nociceptive flexor (RIII) reflex and the conditioned pain modulation (CPM) paradigm, and on supraspinal nociceptive responses, assessed by pain intensity and unpleasantness ratings and late somatosensory evoked potentials (SEPs), in healthy subjects.

Background: Non-invasive vagus nerve stimulation (nVNS) showed promising effects on headache and pain treatment. Underlying mechanisms are only incompletely understood but may include the activation of the descending pain inhibitory system and/or the modification of emotional responses to pain.

Methods: Twenty-seven adult, healthy, and pain-free subjects participated in this double-blind cross-over study conducted at a university research center. They received 4 minutes of cervical nVNS or sham stimulation in randomized order. RIII reflexes, pain ratings, and SEPs were assessed before, during, and 5, 15, 30, and 60 minutes after nVNS/sham stimulation, followed by CPM testing. The primary outcome was the nVNS effect on the RIII reflex size. Three subjects were excluded after the preparatory session (before randomization), 1 subject was excluded after outlier analysis, leaving 23 for analysis.

Results: RIII reflex areas were 917.1 ± 563.8 µV × ms (mean ± SD) before, 952.4 ± 467.4 µV × ms during and 929.2 ± 484.0 µV × ms immediately after nVNS and 858.4 ± 489.2 µV × ms before, 913.9 ± 539.7 µV × ms during and 862.4 ± 476.0 µV × ms after sham stimulation, revealing no differences between the immediate effects of nVNS and sham stimulation (F  = 0.67, P = .574). There also were no effects of nVNS over sham on RIII reflex areas up to 60 minutes after nVNS (F  = 1.29, P = .283). Similarly, there was no statistically significant effect of nVNS on pain intensity ratings and thresholds, RIII reflex thresholds, late SEP amplitudes, and the CPM effect, compared to sham. Pain unpleasantness ratings statistically significantly decreased from 4.4 ± 2.4 (NRS 0-10) to 4.1 ± 2.5 during nVNS compared to sham stimulation (F  = 8.74, P = .007), but there were no longer lasting effects (5-60 minutes after stimulation).

Conclusions: The present study does not support an acute effect of nVNS on descending pain inhibition, pain intensity perception or supraspinal nociception in healthy adults. However, there was a small effect on pain unpleasantness during nVNS, suggesting that nVNS may preferentially act on affective, not somatosensory pain components.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/head.13891DOI Listing
September 2020

The Use of Non-invasive Vagus Nerve Stimulation to Treat Respiratory Symptoms Associated With COVID-19: A Theoretical Hypothesis and Early Clinical Experience.

Neuromodulation 2020 Aug 12;23(6):784-788. Epub 2020 May 12.

Anesthesia Pain Care Consultants, Tamarac, FL, USA.

Objectives: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pandemic with no specific therapeutic agents and substantial mortality, and finding new treatments is critical. Most cases are mild, but a significant minority of patients develop moderate to severe respiratory symptoms, with the most severe cases requiring intensive care and/or ventilator support. This respiratory compromise appears to be due to a hyperimmune reaction, often called a cytokine storm. Vagus nerve stimulation has been demonstrated to block production of cytokines in sepsis and other medical conditions. We hypothesize that non-invasive vagus nerve stimulation (nVNS) might provide clinical benefits in patients with respiratory symptoms similar to those associated with COVID-19.

Materials And Methods: Information on two case reports was obtained via email correspondence and phone interviews with the patients.

Results: Both patients reported clinically meaningful benefits from nVNS therapy. In case 1, the patient used nVNS to expedite symptomatic recovery at home after hospital discharge and was able to discontinue use of opioid and cough suppressant medications. In case 2, the patient experienced immediate and consistent relief from symptoms of chest tightness and shortness of breath, as well as an improved ability to clear his lungs.

Conclusions: Preliminary observations and a strong scientific foundation suggest that nVNS might provide clinical benefits in patients with COVID-19 via multiple mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ner.13172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267613PMC
August 2020

Patient experience with non-invasive vagus nerve stimulator: gammaCore patient registry.

Am J Manag Care 2020 02;26(1 Suppl):S15-S19

profecyINTEL, LLC, Bridgewater, NJ. Email:

gammaCore is cleared by the FDA for acute and preventive treatment of cluster headache and the acute treatment of migraine in adults. Previously, only 2 treatments were approved for acute treatment of cluster headache while none were approved for preventive treatment. Following the initial FDA clearance, based on the ACT-1 and ACT-2 studies, a gammaCore Patient Registry (GPR) was designed to provide insights on the use of gammaCore and prescription patterns in the real-world setting and to characterize respective benefits and challenges during the acute treatment of episodic cluster headache. GPR was a prospective observational registry in which patients with episodic cluster headache (3rd edition of the International Classification of Headache Disorders criteria) who were prescribed gammaCore were invited to voluntarily enroll and provide information on their experiences between July 2017 and June 2018. Participants provided baseline information and were trained to self-administer treatment with gammaCore for cluster pain. Participants were also requested to record information for each cluster attack. Of the 182 patients who provided baseline demographic and cluster headache characteristics, 152 provided health index baseline data using EuroQol Health Index tool, 5-level format (EQ5D-5L) and 17 patients provided attack data on a total of 192 cluster headache attacks. The mean age was 49 years; 65% were male and 82% were white; the mean number of months of known diagnosis of cluster headache was 57; the mean number of attacks per cluster headache 4-week period was 14; and the mean pain score was 3.7 (0-4 scale) with a mean attack duration of 74 minutes. Sixty-seven percent of patients had used preventive treatments and 83% had used abortive treatments for cluster headaches; 25% of participants reported at least 1 comorbidity. The mean EQ5D-5L score (scale 0-1) was 0.83. Of the 192 cluster headache attacks reported, gammaCore was used in 116 (60%) attacks. Within this group, the mean pain score at the start of the attacks was 2.7, the mean number of stimulations used was 3.6, and the pain score after 30 minutes was 1.3. At 30 minutes, the pain of 81 (70%) attacks was reduced to none (27%) or mild (43%) (a pain score of 0 or 1) and in 94 (81%) attacks, patients experienced a reduction of at least 1 point in the pain score. This real-world observational evidence suggests that gammaCore adds clinically meaningful value to patients with episodic cluster headache by providing rapid pain relief and confirms that there is significant interest among prescribers in providing this new treatment and technology. This evidence further supports the need to redefine gammaCore as no longer investigational or experimental during considerations for reimbursement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.37765/ajmc.2020.42545DOI Listing
February 2020

Real-world assessment of concomitant opioid utilization and associated trends in patients with migraine.

Am J Manag Care 2020 02;26(1 Suppl):S8-S14

Magellan Method, a Division of Magellan Rx Management, Middletown, RI. Email:

Migraine is a debilitating condition that affects approximately 16% of adults and is the fifth leading cause of emergency department visits in the United States. There are several treatment options for migraines; opioids are frequently prescribed. Results from a recent study showed that more than half of the patients with chronic migraine and a third of the patients with episodic migraine received an opioid prescription in the past year. The American Headache Society recognizes the magnitude of this issue and is working to educate providers on the danger of prescribing opioids in the migraine population The objective of this article is to assess the utilization trends of prescription opioid products and evaluate the impact of opioid utilization on healthcare costs in this patient population. This retrospective claims database analysis used real-world medical claims from multiple health plans. The study period was from January 1, 2009, to September 30, 2017. Patients were included if they were 18 years or older and continuously enrolled in the study period for at least 3 years. Patients were included in the migraine cohort if they had any diagnosis of migraine headache during the study period, while patients without a headache related diagnosis were included in the control cohort. Control patients were propensity matched 1:1 to migraine patients. Discrete (count) data are represented by frequencies and percentages. Continuous results are presented as means, medians, and standard deviations. In the study, 107,216 patients met the inclusion criteria, with 53,608 assigned to each cohort. In the migraine and control cohorts, respectively, 28% and 11% were prescribed opioids. In both cohorts, a majority of the patients were female (81.8%). In both cohorts, opioid use was associated with higher total costs compared with patients who were not prescribed opioids: $82,007 for 200 morphine milligram equivalents (MME)/day or more versus $19,792 for no opioid in patients with migraine; and $54,200 for 200 MME/day or more versus $12,060 for no opioid use in control patients; P <.0001. Patients with more than 2 comorbidities who were prescribed opioids had higher costs than patients with more than 2 comorbidities who were not prescribed opioids and patients with less than 2 comorbidities who were prescribed opioids ($65,980, $32,152, and $35,964, respectively, for patients with migraine, and $52,883, $24,641, and $35,748, respectively, for control patients; P <.0001). Patients with migraine have more than twice the healthcare costs as patients without migraines. The additional increase in healthcare costs in patients with migraine who use opioids for treatment and/or have 2 or more comorbidities is significant. Control of the pain associated with migraine, specifically among those with multiple comorbid conditions, may contribute to substantial reductions in healthcare costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.37765/ajmc.2020.42544DOI Listing
February 2020

Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial.

Cephalalgia 2019 Oct 15;39(12):1475-1487. Epub 2019 Sep 15.

Leiden University Medical Center, Leiden, The Netherlands.

Introduction: Non-invasive vagus nerve stimulation (nVNS; gammaCore®) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data.

Methods: This multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-week open-label period of nVNS. Patients were to administer two 120-second stimulations bilaterally to the neck three times daily (6-8 hours apart).

Results: Of 477 enrolled patients, 332 comprised the intent-to-treat (ITT) population. Mean reductions in migraine days per month (primary outcome) were 2.26 for nVNS (n = 165; baseline, 7.9 days) and 1.80 for sham (n = 167; baseline, 8.1 days) ( = 0.15). Results were similar across other outcomes. Upon observation of suboptimal adherence rates, post hoc analysis of patients with ≥ 67% adherence per month demonstrated significant differences between nVNS (n = 138) and sham (n = 140) for outcomes including reduction in migraine days (2.27 vs. 1.53;  = 0.043); therapeutic gains were greater in patients with aura than in those without aura. Most nVNS device-related adverse events were mild and transient, with application site discomfort being the most common.

Conclusions: Preventive nVNS treatment in episodic migraine was not superior to sham stimulation in the ITT population. The "sham" device inadvertently provided a level of active vagus nerve stimulation. Post hoc analysis showed significant effects of nVNS in treatment-adherent patients. PREMIUM; NCT02378844; https://clinicaltrials.gov/ct2/show/NCT02378844.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0333102419876920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791025PMC
October 2019

Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A meta-analysis.

Cephalalgia 2019 Jul 10;39(8):967-977. Epub 2019 Jun 10.

2 NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, UK.

Background: Two randomized, double-blind, sham-controlled trials (ACT1, ACT2) evaluated non-invasive vagus nerve stimulation (nVNS) as acute treatment for cluster headache. We analyzed pooled ACT1/ACT2 data to increase statistical power and gain insight into the differential efficacy of nVNS in episodic and chronic cluster headache.

Methods: Data extracted from ACT1 and ACT2 were pooled using a fixed-effects model. Main outcome measures were the primary endpoints of each study. This was the proportion of participants whose first treated attack improved from moderate (2), severe (3), or very severe (4) pain intensity to mild (1) or nil (0) for ACT1 and the proportion of treated attacks whose pain intensity improved from 2-4 to 0 for ACT2.

Results: The pooled population included 225 participants (episodic: n = 112; chronic: n = 113) from ACT1 (n = 133) and ACT2 (n = 92) in the nVNS (n = 108) and sham (n = 117) groups. Interaction was shown between treatment group and cluster headache subtype ( < 0.05). nVNS was superior to sham in episodic but not chronic cluster headache (both endpoints  < 0.01). Only four patients discontinued the studies due to adverse events.

Conclusions: nVNS is a well-tolerated and effective acute treatment for episodic cluster headache.

Trial Registration: The studies were registered at clinicaltrials.gov (ACT1: NCT01792817; ACT2: NCT01958125).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0333102419856607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637721PMC
July 2019

Non-invasive neuromodulation for migraine and cluster headache: a systematic review of clinical trials.

J Neurol Neurosurg Psychiatry 2019 07 1;90(7):796-804. Epub 2019 Mar 1.

Headache and Craniofacial Pain Unit, Neurology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.

Non-invasive neuromodulation therapies for migraine and cluster headache are a practical and safe alternative to pharmacologics. Comparisons of these therapies are difficult because of the heterogeneity in study designs. In this systematic review of clinical trials, the scientific rigour and clinical relevance of the available data were assessed to inform clinical decisions about non-invasive neuromodulation. PubMed, Cochrane Library and ClinicalTrials.gov databases and the WHO's International Clinical Trials Registry Platform were searched for relevant clinical studies of non-invasive neuromodulation devices for migraine and cluster headache (1 January 1990 to 31 January 2018), and 71 were identified. This analysis compared study designs using recommendations of the International Headache Society for pharmacological clinical trials, the only available guidelines for migraine and cluster headache. Non-invasive vagus nerve stimulation (nVNS), single-transcranial magnetic stimulation and external trigeminal nerve stimulation (all with regulatory clearance) were well studied compared with the other devices, for which studies frequently lacked proper blinding, sham controls and sufficient population sizes. nVNS studies demonstrated the most consistent adherence to available guidelines. Studies of all neuromodulation devices should strive to achieve the same high level of scientific rigour to allow for proper comparison across devices. Device-specific guidelines for migraine and cluster headache will be soon available, but adherence to current guidelines for pharmacological trials will remain a key consideration for investigators and clinicians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2018-320113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585264PMC
July 2019

Correction to: Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial.

J Headache Pain 2018 12 18;19(1):120. Epub 2018 Dec 18.

Neurophysiology and Pain Unit, University of Bari Aldo Moro, Bari, Italy.

Following publication of the original article [1], the authors notified us o that the Table 1 citation within the legend was not presented as initially requested.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-018-0949-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755543PMC
December 2018

Non-invasive vagus nerve stimulation for treatment of cluster headache: early UK clinical experience.

J Headache Pain 2018 Nov 23;19(1):114. Epub 2018 Nov 23.

University Hospitals of North Midlands, Newcastle Road, Stoke-on-Trent, ST4 6QG, UK.

Background: Evidence supports the use of non-invasive vagus nerve stimulation (nVNS; gammaCore®) as a promising therapeutic option for patients with cluster headache (CH). We conducted this audit of real-world data from patients with CH, the majority of whom were treatment refractory, to explore early UK clinical experience with nVNS used acutely, preventively, or both.

Methods: We retrospectively analysed data from 30 patients with CH (29 chronic, 1 episodic) who submitted individual funding requests for nVNS to the National Health Service. All patients had responded to adjunctive nVNS therapy during an evaluation period (typical duration, 3-6 months). Data collected from patient interviews, treatment diaries, and physician notes were summarised with descriptive statistics. Paired t tests were used to examine statistical significance.

Results: The mean (SD) CH attack frequency decreased from 26.6 (17.1) attacks/wk. before initiation of nVNS therapy to 9.5 (11.0) attacks/wk. (P < 0.01) afterward. Mean (SD) attack duration decreased from 51.9 (36.7) minutes to 29.4 (28.5) minutes (P < 0.01), and mean (SD) attack severity (rated on a 10-point scale) decreased from 7.8 (2.3) to 6.0 (2.6) (P < 0.01). Use of abortive treatments also decreased. Favourable changes in the use of preventive medication were also observed. No serious device-related adverse events were reported.

Conclusions: Significant decreases in attack frequency, severity, and duration were observed in these patients with CH who did not respond to or were intolerant of multiple preventive and/or acute treatments. These real-world findings complement evidence from clinical trials demonstrating the efficacy and safety of nVNS in CH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-018-0936-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755582PMC
November 2018

Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial.

J Headache Pain 2018 Nov 1;19(1):101. Epub 2018 Nov 1.

Neurophysiology and Pain Unit, University of Bari Aldo Moro, Bari, Italy.

Background: Non-invasive vagus nerve stimulation (nVNS) has been shown to be practical, safe, and well tolerated for treating primary headache disorders. The recent multicenter, randomized, double-blind, sham-controlled PRESTO trial provided Class I evidence that for patients with episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. We report additional pre-defined secondary and other end points from PRESTO that demonstrate the consistency and durability of nVNS efficacy across a broad range of outcomes.

Methods: After a 4-week observation period, 248 patients with episodic migraine with/without aura were randomly assigned to acute treatment of migraine attacks with nVNS (n = 122) or a sham device (n = 126) during a double-blind period lasting 4 weeks (or until the patient had treated 5 attacks). All patients received nVNS therapy during the subsequent 4-week/5-attack open-label period.

Results: The intent-to-treat population consisted of 243 patients. The nVNS group (n = 120) had a significantly greater percentage of attacks treated during the double-blind period that were pain-free at 60 (P = 0.005) and 120 min (P = 0.026) than the sham group (n = 123) did. Similar results were seen for attacks with pain relief at 60 (P = 0.025) and 120 min (P = 0.018). For the first attack and all attacks, the nVNS group had significantly greater decreases (vs sham) in pain score from baseline to 60 min (P = 0.029); the decrease was also significantly greater for nVNS at 120 min for the first attack (P = 0.011). Results during the open-label period were consistent with those of the nVNS group during the double-blind period. The incidence of adverse events (AEs) and adverse device effects was low across all study periods, and no serious AEs occurred.

Conclusions: These results further demonstrate that nVNS is an effective and reliable acute treatment for multiple migraine attacks, which can be used safely while preserving the patient's option to use traditional acute medications as rescue therapy, possibly decreasing the risk of medication overuse. Together with its practicality and optimal tolerability profile, these findings suggest nVNS has value as a front-line option for acute treatment of migraine.

Trial Registration: ClinicalTrials.gov identifier: NCT02686034 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-018-0929-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755599PMC
November 2018

Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial.

J Headache Pain 2018 Oct 19;19(1):98. Epub 2018 Oct 19.

Headache and Pain Unit, IRCCS San Raffaele Pisana, Rome, Italy.

Background: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication.

Methods: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation.

Results: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037).

Conclusions: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events.

Trial Registration: ClinicalTrials.gov identifier: NCT02686034 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-018-0928-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742918PMC
October 2018

Effect of Non-invasive Vagus Nerve Stimulation on Resting-State Electroencephalography and Laser-Evoked Potentials in Migraine Patients: Mechanistic Insights.

Front Hum Neurosci 2018 13;12:366. Epub 2018 Sep 13.

Applied Neurophysiology and Pain Unit, SMBNOS Department, Polyclinic General Hospital, Bari Aldo Moro University, Bari, Italy.

A recent multicenter trial provided Class I evidence that for patients with an episodic migraine, non-invasive vagus nerve stimulation (nVNS) significantly increases the probability of having mild pain or being pain-free 2 h post-stimulation. Here we aimed to investigate the potential effect of nVNS in the modulation of spontaneous and pain related bioelectrical activity in a subgroup of migraine patients enrolled in the PRESTO trial by using resting-state electroencephalography and trigeminal laser-evoked potentials (LEPs). LEPs were recorded for 27 migraine patients who received active or sham nVNS over the cervical vagus nerve. We measured power values for frequencies between 1-100 Hz in a resting-state condition and the latency and amplitude of N1, N2, and P2 components of LEPs in a basal condition during and after active or sham vagus nerve stimulation (T0, T1, T2). The P2 evoked by the right and the left trigeminal branch was smaller during active nVNS. The sham device also attenuated the P2 amplitude evoked by the left trigeminal branch at T1 and T2, but this attenuation did not reach significance. No changes were observed for N1 amplitude, N1, N2, P2 latency, or pain rating. nVNS induced an increase of EEG power in both slow and fast rhythms, but this effect was not significant as compared to the sham device. These findings suggest that nVNS acts on the cortical areas that are responsible for trigeminal pain control and pave the ground for future studies aimed at confirming the possible correlations with clinical outcomes, including the effect on symptoms that are directly correlated with trigeminal pain processing and modulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnhum.2018.00366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146235PMC
September 2018

Noninvasive vagus nerve stimulation as acute therapy for migraine: The randomized PRESTO study.

Neurology 2018 07 15;91(4):e364-e373. Epub 2018 Jun 15.

From the Headache Science Centre (C.T.), IRCCS C. Mondino Foundation, Pavia; University of Pavia (C.T.); Headache Center (L.G.), Carlo Besta Neurological Institute and Foundation, Milan; Neurophysiology and Pain Unit (M.d.T.), University of Bari Aldo Moro; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) (G.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Clinical and Molecular Medicine (P.M.), Sapienza University, Rome; Department of Neuroscience (I.R.), University of Turin, Italy; MedLogix Communications, LLC (S.D.), Itasca IL; Headache Centre (P.G.), University Hospital of Careggi, Florence; IRCCS Neuromed (A.A.), Pozzilli (IS); Neurologic Clinic (P.S.), Santa Maria della Misericordia Hospital, Perugia, Italy; electroCore, LLC (E.L.), Basking Ridge, NJ; and Headache and Pain Unit (P.B.), IRCCS San Raffaele Pisana, Rome, Italy.

Objective: To evaluate the efficacy, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS; gammaCore; electroCore, LLC, Basking Ridge, NJ) for the acute treatment of migraine in a multicenter, double-blind, randomized, sham-controlled trial.

Methods: A total of 248 participants with episodic migraine with/without aura were randomized to receive nVNS or sham within 20 minutes from pain onset. Participants were to repeat treatment if pain had not improved in 15 minutes.

Results: nVNS (n = 120) was superior to sham (n = 123) for pain freedom at 30 minutes (12.7% vs 4.2%; = 0.012) and 60 minutes (21.0% vs 10.0%; = 0.023) but not at 120 minutes (30.4% vs 19.7%; = 0.067; primary endpoint; logistic regression) after the first treated attack. A post hoc repeated-measures test provided further insight into the therapeutic benefit of nVNS through 30, 60, and 120 minutes (odds ratio 2.3; 95% confidence interval 1.2, 4.4; = 0.012). nVNS demonstrated benefits across other endpoints including pain relief at 120 minutes and was safe and well-tolerated.

Conclusion: This randomized sham-controlled trial supports the abortive efficacy of nVNS as early as 30 minutes and up to 60 minutes after an attack. Findings also suggest effective pain relief, tolerability, and practicality of nVNS for the acute treatment of episodic migraine.

Clinicaltrialsgov Identifier: NCT02686034.

Classification Of Evidence: This study provides Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 hours poststimulation (absolute difference 13.2%).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000005857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070381PMC
July 2018

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

Cephalalgia 2018 04 12;38(5):959-969. Epub 2017 Dec 12.

2 Leiden University Medical Centre, Leiden, the Netherlands.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0333102417744362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896689PMC
April 2018

Peripheral vagal nerve stimulation modulates the nociceptive withdrawal reflex in healthy subjects: A randomized, cross-over, sham-controlled study.

Cephalalgia 2018 09 20;38(10):1658-1664. Epub 2017 Nov 20.

1 Headache Science Centre, C. Mondino National Neurological Institute, Pavia, Italy.

Introduction The mechanism of action of non-invasive vagal nerve stimulation in the treatment of migraine is elusive. We studied its effect in a human model of pain, the nociceptive withdrawal reflex. Methods We enrolled 10 healthy subjects who underwent active non-invasive vagal nerve stimulation and sham treatment in a randomized, cross-over, sham-controlled study. Non-invasive vagal nerve stimulation was delivered with gammaCore®. The assessment of the nociceptive withdrawal reflex was performed at baseline (T0) and at 5 (T5) and 30 (T30) minutes after stimulation. Results Non-invasive vagal nerve stimulation significantly increased the reflex threshold to single stimulus at both T5 and T30 and the temporal summation threshold at T30. Sham treatment did not modify any parameters. Discussion These findings are consistent with a modulation of central descending pathways for pain control. An altered spinal and supraspinal control of pain has been described in primary headache, so this effect may partially explain the therapeutic effect of non-invasive vagal nerve stimulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0333102417742347DOI Listing
September 2018

Cost-effectiveness of gammaCore (non-invasive vagus nerve stimulation) for acute treatment of episodic cluster headache.

Am J Manag Care 2017 Nov;23(16 Suppl):S300-S306

Cluster headache is a debilitating disease characterized by excruciatingly painful attacks that affects 0.15% to 0.4% of the US population. Episodic cluster headache manifests as circadian and circannual seasonal bouts of attacks, each lasting 15 to 180 minutes, with periods of remission. In chronic cluster headache, the attacks occur throughout the year with no periods of remission. While existing treatments are effective for some patients, many patients continue to suffer. There are only 2 FDA-approved medications for episodic cluster headache in the United States, while others, such as high-flow oxygen, are used off-label. Episodic cluster headache is associated with comorbidities and affects work, productivity, and daily functioning. The economic burden of episodic cluster headache is considerable, costing more than twice that of nonheadache patients. gammaCore adjunct to standard of care (SoC) was found to have superior efficacy in treatment of acute episodic cluster headaches compared with sham-gammaCore used with SoC in ACT1 and ACT2 trials. However, the economic impact has not been characterized for this indication. We conducted a cost-effectiveness analysis of gammaCore adjunct to SoC compared with SoC alone for the treatment of acute pain associated with episodic cluster headache attacks. The model structure was based on treatment of acute attacks with 3 outcomes: failures, nonresponders, and responders. The time horizon of the model is 1 year using a payer perspective with uncertainty incorporated. Parameter inputs were derived from primary data from the randomized controlled trials for gammaCore. The mean annual costs associated with the gammaCore-plus-SoC arm was $9510, and mean costs for the SoC-alone arm was $10,040. The mean quality-adjusted life years for gammaCore-plus-SoC arm were 0.83, and for the SoC-alone arm, they were 0.74. The gammaCore-plus-SoC arm was dominant over SoC alone. All 1-way and multiway sensitivity analyses were cost-effective using a threshold of $20,000. gammaCore dominance, representing savings, was driven by superior efficacy, improvement in quality of life (QoL), and reduction in costs associated with successful and consistent abortion of episodic attacks. These findings serve as additional economic evidence to support coverage for gammaCore. Additional real-world data are needed to characterize the long-term impact of gammaCore on comorbidities, utilization, QoL, daily functioning, productivity, and social engagement of these patients, and for other indications.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2017

Review of non-invasive vagus nerve stimulation (gammaCore): efficacy, safety, potential impact on comorbidities, and economic burden for episodic and chronic cluster headache.

Am J Manag Care 2017 Nov;23(17 Suppl):S317-S325

The FDA has cleared gammaCore (non-invasive vagus nerve stimulator [nVNS]) for the treatment of episodic cluster headache (eCH). With the exception of subcutaneous sumatriptan, all other treatments are used off label and have many limitations. The FDA approval process for devices differs from that of drugs. We performed a review of the literature to evaluate new evidence on various aspects of gammaCore treatment and impact. The ACute Treatment of Cluster Headache Studies (ACT1 and ACT2), both double-blind sham-controlled randomized trials, did not meet the primary endpoints of the trials but each demonstrated significant superiority of gammaCore among patients with eCH. In ACT1, gammaCore resulted in a higher response rate (RR) (RR, 3.2; 95% CI, 1.6-8.2; P = .014), higher pain-free rate for >50% of attacks (RR, 2.3; 95% CI, 1.1-5.2; P = .045), and shorter duration of attacks (mean difference [MD], -30 minutes; P <.01) compared with the sham group. In ACT2, gammaCore resulted in higher odds of achieving pain-free attacks in 15 minutes (OR, 9.8; 95% CI, 2.2-44.1; P = .01), lower pain intensity in 15 minutes (MD, -1.1; P <.01), and higher rate of achieving responder status at 15 minutes for ≥50% of treated attacks (RR, 2.8; 95% CI, 1.0-8.1; P = .058) compared with the sham group. The PREVention and Acute Treatment of Chronic Cluster Headache (PREVA) study also demonstrated that gammaCore plus standard of care (SOC) was superior to SOC alone in patients with chronic cluster headache (CH). Medical costs, pharmacy refills, and pharmacy costs were higher in patients coded for CH in claims data compared with controls with nonheadache codes. gammaCore is easy to use, practical, and safe; delivery cannot be wasted; and patients prefer using gammaCore compared with SOC. The treatment improves symptoms and reduces the need for CH rescue medications. Current US reimbursement policies, which predate nVNS and are based on expensive, surgically implanted, and permanent implanted vagus nerve stimulation (iVNS), need to be modified to distinguish nVNS from iVNS. gammaCore, cleared by the FDA in April 2017, provides substantial value to patients and also to payers. There is sufficient evidence to support the need to modify current reimbursement policies to include coverage for gammaCore (nVNS) for eCH.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2017

Proof of concept: short-term non-invasive cervical vagus nerve stimulation in patients with drug-refractory gastroparesis.

Frontline Gastroenterol 2017 Oct 24;8(4):325-330. Epub 2017 May 24.

Royal Free London NHS Foundation Trust, London, UK.

Background: Gastric electric stimulation (GES) is a treatment approach to refractory gastroparesis, possibly acting centrally via afferent vagus nerve stimulation (VNS). Non-invasive VNS (nVNS) is a potential alternative to GES that could eliminate the safety risks of or identify likely responders to implantable neurostimulators.

Objective: This open-label proof-of-concept study assessed the effects of nVNS in patients with severe drug-refractory gastroparesis.

Methods: Patients used the Gastroparesis Cardinal Symptom Index (GCSI) to grade symptoms in diaries daily for 2 weeks before treatment (baseline) and during ≥3 weeks of nVNS therapy. Adverse events (AEs) were also diarised. Treatment was self-administered using an nVNS device (gammaCore, electroCore) and consisted of 120 s stimulations to the vagus nerve in the neck (two stimulations to each side three times daily during weeks 1 and 2; three stimulations to each side three times daily during week 3 and beyond). was defined as a ≥1 point decrease from baseline in GCSI score.

Results: Thirty-five patients enrolled; 23 were compliant with study procedures and were included in the analysis; 7 continued treatment beyond 3 weeks. Response rates were 35% (8/23) at 3 weeks and 43% (10/23) for the duration of therapy (3-6 weeks). For the entire cohort and the 10 responders, improvements from baseline were noted for mean total GCSI and GCSI subscale scores (nausea/vomiting, postprandial fullness/early satiety, bloating). No serious AEs were reported.

Conclusions: These preliminary results provide a signal that nVNS may be useful for treating refractory gastroparesis. Larger controlled studies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/flgastro-2017-100809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641854PMC
October 2017

Non-invasive vagus nerve stimulation (nVNS) as symptomatic treatment of migraine in young patients: a preliminary safety study.

Neurol Sci 2017 May;38(Suppl 1):197-199

Headache and Pain Unit, Department of Neurological Motor and Sensorial Science, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Pisana, Rome, Italy.

Recent clinical experiences and clinical trials have demonstrated the safety, tolerability, and efficacy of non-invasive vagus nerve stimulation (nVNS; gammaCore) for the acute and prophylactic treatment of migraine. nVNS has a favorable adverse event profile, making it an attractive option for sensitive patient populations. We explored the safety, tolerability, and efficacy of nVNS as acute migraine treatment in adolescents. A group of adolescent patients suffering from migraine without aura were trained to use gammaCore to manage their migraine attacks. 46.8% of the treated migraine attacks (22/47) were considered successfully treated and did not require any rescue medication. No device-related adverse events were recorded. This preliminary study suggests that nVNS may represent a safe, well-tolerated, and effective for acute migraine treatment in adolescents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-017-2942-5DOI Listing
May 2017

Effects of non-invasive vagus nerve stimulation on attack frequency over time and expanded response rates in patients with chronic cluster headache: a post hoc analysis of the randomised, controlled PREVA study.

J Headache Pain 2017 Dec 14;18(1):22. Epub 2017 Feb 14.

Department of Neurology, Ludwig-Maximilian University, Marchioninistr 15, Munich, D81377, Germany.

Background: In the PREVention and Acute treatment of chronic cluster headache (PREVA) study, attack frequency reductions from baseline were significantly more pronounced with non-invasive vagus nerve stimulation plus standard of care (nVNS + SoC) than with SoC alone. Given the intensely painful and frequent nature of chronic cluster headache attacks, additional patient-centric outcomes, including the time to and level of therapeutic response, were evaluated in a post hoc analysis of the PREVA study.

Findings: After a 2-week baseline phase, 97 patients with chronic cluster headache entered a 4-week randomised phase to receive nVNS + SoC (n = 48) or SoC alone (n = 49). All 92 patients who continued into a 4-week extension phase received nVNS + SoC. Compared with SoC alone, nVNS + SoC led to a significantly lower mean weekly attack frequency by week 2 of the randomised phase; the attack frequency remained significantly lower in the nVNS + SoC group through week 3 of the extension phase (P < 0.02). Attack frequencies in the nVNS + SoC group were significantly lower at all study time points than they were at baseline (P < 0.05). Response rates were significantly greater with nVNS + SoC than with SoC alone when response was defined as attack frequency reductions of ≥25%, ≥50%, and ≥75% from baseline (≥25% and ≥50%, P < 0.001; ≥75%, P = 0.009). The 100% response rate was 8% with nVNS + SoC and 0% with SoC alone.

Conclusions: Prophylactic nVNS led to rapid, significant, and sustained reductions in chronic cluster headache attack frequency within 2 weeks after its addition to SoC and was associated with significantly higher ≥25%, ≥50%, and ≥75% response rates than SoC alone. The rapid decrease in weekly attack frequency justifies a 4-week trial period to identify responders to nVNS, with a high degree of confidence, among patients with chronic cluster headache.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-017-0731-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309191PMC
December 2017

Non-invasive Vagus Nerve Stimulation (nVNS) as mini-prophylaxis for menstrual/menstrually related migraine: an open-label study.

J Headache Pain 2016 Dec 3;17(1):91. Epub 2016 Oct 3.

Headache and Pain Unit, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Pisana, Via della Pisana 235, 00163, Rome, Italy.

Background: Menstrual migraine and menstrually related migraine attacks are typically longer, more disabling, and less responsive to medications than non-menstrual attacks. The aim of this study was to evaluate the efficacy, safety, and tolerability of non-invasive vagus nerve stimulation for the prophylactic treatment of menstrual migraine/menstrually related migraine.

Methods: Fifty-six enrolled subjects (menstrual migraine, 9 %; menstrually related migraine, 91 %), 33 (59 %) of whom were receiving other prophylactic therapies, entered a 12-week baseline period. Fifty-one subjects subsequently entered a 12-week treatment period to receive open-label prophylactic non-invasive vagus nerve stimulation adjunctively (31/51; 61 %) or as monotherapy (20/51; 39 %) on day -3 before estimated onset of menses through day +3 after the end of menses.

Results: The number of menstrual migraine/menstrually related migraine days per month was significantly reduced from baseline (mean ± standard error, 7.2 ± 0.7 days) to the end of treatment (mean ± standard error, 4.7 ± 0.5 days; P < 0.001) (primary end point). Of all subjects, 39 % (95 % confidence interval: 26 %, 54 %) (20/51) had a ≥ 50 % reduction (secondary end point). For the other secondary end points, clinically meaningful reductions in analgesic use (mean change ± standard error, -3.3 ± 0.6 times per month; P < 0.001), 6-item Headache Impact Test score (mean change ± standard error, -3.1 ± 0.7; P < 0.001), and Migraine Disability Assessment score (mean change ± standard error, -11.9 ± 3.4; P < 0.001) were observed, along with a modest reduction in pain intensity (mean change ± standard error, -0.5 ± 0.2; P = 0.002). There were no safety/tolerability concerns.

Conclusions: These findings suggest that non-invasive vagus nerve stimulation is an effective treatment that reduces the number of menstrual migraine/menstrually related migraine days and analgesic use without safety/tolerability concerns in subjects with menstrual migraine/menstrually related migraine. Randomised controlled studies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-016-0684-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047863PMC
December 2016

Non-Invasive Vagus Nerve Stimulation for the ACute Treatment of Cluster Headache: Findings From the Randomized, Double-Blind, Sham-Controlled ACT1 Study.

Headache 2016 Sep;56(8):1317-32

Department of Neurology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.

Objective: To evaluate non-invasive vagus nerve stimulation (nVNS) as an acute cluster headache (CH) treatment.

Background: Many patients with CH experience excruciating attacks at a frequency that is not sufficiently addressed by current symptomatic treatments.

Methods: One hundred fifty subjects were enrolled and randomized (1:1) to receive nVNS or sham treatment for ≤1 month during a double-blind phase; completers could enter a 3-month nVNS open-label phase. The primary end point was response rate, defined as the proportion of subjects who achieved pain relief (pain intensity of 0 or 1) at 15 minutes after treatment initiation for the first CH attack without rescue medication use through 60 minutes. Secondary end points included the sustained response rate (15-60 minutes). Subanalyses of episodic cluster headache (eCH) and chronic cluster headache (cCH) cohorts were prespecified.

Results: The intent-to-treat population comprised 133 subjects: 60 nVNS-treated (eCH, n = 38; cCH, n = 22) and 73 sham-treated (eCH, n = 47; cCH, n = 26). A response was achieved in 26.7% of nVNS-treated subjects and 15.1% of sham-treated subjects (P = .1). Response rates were significantly higher with nVNS than with sham for the eCH cohort (nVNS, 34.2%; sham, 10.6%; P = .008) but not the cCH cohort (nVNS, 13.6%; sham, 23.1%; P = .48). Sustained response rates were significantly higher with nVNS for the eCH cohort (P = .008) and total population (P = .04). Adverse device effects (ADEs) were reported by 35/150 (nVNS, 11; sham, 24) subjects in the double-blind phase and 18/128 subjects in the open-label phase. No serious ADEs occurred.

Conclusions: In one of the largest randomized sham-controlled studies for acute CH treatment, the response rate was not significantly different (vs sham) for the total population; nVNS provided significant, clinically meaningful, rapid, and sustained benefits for eCH but not for cCH, which affected results in the total population. This safe and well-tolerated treatment represents a novel and promising option for eCH. ClinicalTrials.gov identifier: NCT01792817.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/head.12896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113831PMC
September 2016

Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study.

Neurology 2016 Aug 13;87(5):529-38. Epub 2016 Jul 13.

From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion.

Objective: To evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks.

Methods: In this first prospective, multicenter, double-blind, sham-controlled pilot study of nVNS in CM prophylaxis, adults with CM (≥15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months). The primary endpoints were safety and tolerability. Efficacy endpoints in the intent-to-treat population included change in the number of headache days per 28 days and acute medication use.

Results: Fifty-nine participants (mean age, 39.2 years; mean headache frequency, 21.5 d/mo) were enrolled. During the randomized phase, tolerability was similar for nVNS (n = 30) and sham treatment (n = 29). Most adverse events were mild/moderate and transient. Mean changes in the number of headache days were -1.4 (nVNS) and -0.2 (sham) (Δ = 1.2; p = 0.56). Twenty-seven participants completed the open-label phase. For the 15 completers initially assigned to nVNS, the mean change from baseline in headache days after 8 months of treatment was -7.9 (95% confidence interval -11.9 to -3.8; p < 0.01).

Conclusions: Therapy with nVNS was well-tolerated with no safety issues. Persistent prophylactic use may reduce the number of headache days in CM; larger sham-controlled studies are needed.

Clinicaltrialsgov Identifier: NCT01667250.

Classification Of Evidence: This study provides Class II evidence that for patients with CM, nVNS is safe, is well-tolerated, and did not significantly change the number of headache days. This pilot study lacked the precision to exclude important safety issues or benefits of nVNS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000002918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970666PMC
August 2016

Cost-effectiveness analysis of non-invasive vagus nerve stimulation for the treatment of chronic cluster headache.

J Headache Pain 2016 22;17:43. Epub 2016 Apr 22.

Department of Neurology and Headache Center, University Hospital Essen, Hufelandstrasse 55, 45122, Essen, Germany.

Background: Cluster headache (CH) is a debilitating condition that is generally associated with substantial health care costs. Few therapies are approved for abortive or prophylactic treatment. Results from the prospective, randomised, open-label PREVA study suggested that adjunctive treatment with a novel non-invasive vagus nerve stimulation (nVNS) device led to decreased attack frequency and abortive medication use in patients with chronic CH (cCH). Herein, we evaluate whether nVNS is cost-effective compared with the current standard of care (SoC) for cCH.

Methods: A pharmacoeconomic model from the German statutory health insurance perspective was developed to estimate the 1-year cost-effectiveness of nVNS + SoC (versus SoC alone) using data from PREVA. Short-term treatment response data were taken from the clinical trial; longer-term response was modelled under scenarios of response maintenance, constant rate of response loss, and diminishing rate of response loss. Health-related quality of life was estimated by modelling EQ-5D™ data from PREVA; benefits were defined as quality-adjusted life-years (QALY). Abortive medication use data from PREVA, along with costs for the nVNS device and abortive therapies (i.e. intranasal zolmitriptan, subcutaneous sumatriptan, and inhaled oxygen), were used to assess health care costs in the German setting.

Results: The analysis resulted in mean expected yearly costs of €7096.69 for nVNS + SoC and €7511.35 for SoC alone and mean QALY of 0.607 for nVNS + SoC and 0.522 for SoC alone, suggesting that nVNS generates greater health benefits for lower overall cost. Abortive medication costs were 23 % lower with nVNS + SoC than with SoC alone. In the alternative scenarios (i.e. constant rate of response loss and diminishing rate of response loss), nVNS + SoC was more effective and cost saving than SoC alone.

Conclusions: In all scenarios modelled from a German perspective, nVNS was cost-effective compared with current SoC, which suggests that adjunctive nVNS therapy provides economic benefits in the treatment of cCH. Notably, the current analysis included only costs associated with abortive treatments. Treatment with nVNS will likely promote further economic benefit when other potential sources of cost savings (e.g. reduced frequency of clinic visits) are considered.

Trial Registration: Clinicaltrials.gov identifier NCT01701245 , 03OCT2012.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-016-0633-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840129PMC
October 2016

Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study.

Cephalalgia 2016 May 21;36(6):534-46. Epub 2015 Sep 21.

Ludwig Maximilian University of Munich, Munich, Germany.

Background: Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demon.strate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was examined as adjunctive prophylactic treatment of chronic CH.

Methods: PREVA was a prospective, open-label, randomised study that compared adjunctive prophylactic nVNS (n = 48) with standard of care (SoC) alone (control (n = 49)). A two-week baseline phase was followed by a four-week randomised phase (SoC plus nVNS vs control) and a four-week extension phase (SoC plus nVNS). The primary end point was the reduction in the mean number of CH attacks per week. Response rate, abortive medication use and safety/tolerability were also assessed.

Results: During the randomised phase, individuals in the intent-to-treat population treated with SoC plus nVNS (n = 45) had a significantly greater reduction in the number of attacks per week vs controls (n = 48) (-5.9 vs -2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; p = 0.02). Higher ≥50% response rates were also observed with SoC plus nVNS (40% (18/45)) vs controls (8.3% (4/48); p < 0.001). No serious treatment-related adverse events occurred.

Conclusion: Adjunctive prophylactic nVNS is a well-tolerated novel treatment for chronic CH, offering clinical benefits beyond those with SoC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0333102415607070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853813PMC
May 2016

Non-invasive vagus nerve stimulation for acute treatment of high-frequency and chronic migraine: an open-label study.

J Headache Pain 2015 30;16:61. Epub 2015 Jun 30.

Headache and Pain Unit, Department of Neurological Motor and Sensorial Sciences, IRCCS San Raffaele Pisana, Via della Pisana 235, 00163, Rome, Italy,

Background: The treatment of migraine headache is challenging given the lack of a standardized approach to care, unsatisfactory response rates, and medication overuse. Neuromodulation therapy has gained interest as an alternative to pharmacologic therapy for primary headache disorders. This study investigated the effects of non-invasive vagus nerve stimulation (nVNS) in patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM).

Findings: In this open-label, single-arm, multicenter study, patients with HFEM or CM self-treated up to 3 consecutive mild or moderate migraine attacks that occurred during a 2-week period by delivering two 120-s doses of nVNS at 3-min intervals to the right cervical branch of the vagus nerve. Of the 50 migraineurs enrolled (CM/HFEM: 36/14), 48 treated 131 attacks. The proportion of patients reporting pain relief, defined as a ≥50% reduction in visual analog scale (VAS) score, was 56.3% at 1 h and 64.6% at 2 h. Of these patients, 35.4% and 39.6% achieved pain-free status (VAS = 0) at 1 and 2 h, respectively. When all attacks (N = 131) were considered, the pain-relief rate was 38.2% at 1 h and 51.1% at 2 h, whereas the pain-free rate was 17.6% at 1 h and 22.9% at 2 h. Treatment with nVNS was safe and well tolerated.

Conclusion: Non-invasive vagus nerve stimulation may be effective as acute treatment for HFEM or CM and may help to reduce medication overuse and medication-associated adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-015-0542-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485661PMC
February 2016
-->