Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study.
; ; et al
in Cephalalgia : An International Journal of Headache (2015)
Background: Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was ... [more ▼]
Background: Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate 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. [less ▲]Detailed reference viewed: 15 (3 ULg)
Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study.
; ; et al
in Lancet Neurology (2012), 11(5), 405-13
BACKGROUND: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a ... [more ▼]
BACKGROUND: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study. We aimed to assess the efficacy and safety of oral lasmiditan for the acute treatment of migraine. METHODS: In this multicentre, double-blind, parallel-group, dose-ranging study in 43 headache centres in five European countries, patients with migraine with and without aura and who were not using prophylaxis were randomly assigned (1:1:1:1:1) to treat one moderate or severe attack at home with 50 mg, 100 mg, 200 mg, or 400 mg lasmiditan, or placebo. Study drug and placebo were supplied in identical numbered tablet packs. The randomisation code was generated by an independent statistician. Patients and investigators were masked to treatment allocation. The primary endpoint was dose response for headache relief (moderate or severe becoming mild or none) at 2 h. The primary analysis was done in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00883051. FINDINGS: Between July 8 2009, and Feb 18, 2010, 512 patients were randomly assigned to treatment, 391 of whom received treatment. 86 patients received placebo (81 included in primary analysis) and 305 received lasmiditan (50 mg n=79, 100 mg n=81, 200 mg n=69, and 400 mg n=68 included in primary analysis). There was a linear association between headache response rate at 2 h and lasmiditan dose (Cochran-Armitage test p<0.0001). Every lasmiditan treatment dose significantly improved headache response at 2 h compared with placebo (lasmiditan 50 mg: difference 17.9%, 95% CI 3.9-32.1, p=0.022; 100 mg: 38.2%, 24.1-52.4, p<0.0001; 200 mg: 28.8%, 9.6-39.9, p=0.0018; 400 mg: 38.7%, 23.9-53.6, p<0.0001). The proportion of patients with treatment-emergent adverse events increased with increasing doses (53/82 [65%], 59/82 [72%], 61/71 [86%], and 59/70 [84%] for lasmiditan 50, 100, 200, and 400 mg, respectively vs 19/86 [22%] for placebo). Most adverse events were mild or moderate in intensity, with 16 of 82 (20%), 23 of 82 (28%), 28 of 71 (39%), and 31 of 70 (44%) of patients on lasmiditan 50, 100, 200, and 400 mg, respectively reporting a severe adverse event compared with five of 86 (6%) on placebo. The most common adverse events were CNS related and included dizziness, fatigue, vertigo, paraesthesia, and somnolence. INTERPRETATION: Oral lasmiditan seems to be safe and effective in the acute treatment of migraine. Further assessment in larger placebo-controlled and triptan-controlled trials are needed to assess the potential role of lasmiditan in acute migraine therapy. FUNDING: CoLucid Pharmaceuticals. [less ▲]Detailed reference viewed: 97 (0 ULg)
Factors predicting the probability of relapse after discontinuation of migraine preventive treatment with topiramate.
Schoenen, Jean ; ; et al
in Cephalalgia : An International Journal of Headache (2010), 30(11), 1290-5
INTRODUCTION: Demographic and clinical variables were examined in a post hoc analysis of the PROlonged Migraine Prevention with Topiramate (PROMPT) study to determine potential contribution to relapse ... [more ▼]
INTRODUCTION: Demographic and clinical variables were examined in a post hoc analysis of the PROlonged Migraine Prevention with Topiramate (PROMPT) study to determine potential contribution to relapse. METHODS: After a six-month open-label (OL) topiramate phase, patients were randomised to continue topiramate or switch to placebo in a six-month double-blind (DB) phase. 'Relapse' was investigated in terms of change in monthly migraine days after randomisation compared with the month before randomisation, and was analysed during the first ('initial relapse') and last month ('sustained relapse') of the DB phase. More than 40 potential predicting factors were entered into analyses of variance and covariance. RESULTS: For initial relapse, variable-by-treatment interactions were significant for the Headache Impact Test (HIT-6) at DB baseline, and decline in acute medication intake or reporting of 'anxiety' in the OL phase. For sustained relapse, no statistically significant interactions were observed. CONCLUSION: Relapse after topiramate discontinuation in migraine prophylaxis appears to be unaffected by patient characteristics or baseline migraine frequency. [less ▲]Detailed reference viewed: 21 (3 ULg)
Cessation versus continuation of 6-month migraine preventive therapy with topiramate (PROMPT): a randomised, double-blind, placebo-controlled trial
; ; et al
in Lancet Neurology (2007), 6(12), 1054-1062
Background Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis ... [more ▼]
Background Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis. We assessed the effects of discontinuation of topiramate after a treatment period of 6 months. Methods 818 patients who have migraines were enrolled from 88 clinics in 21 countries. After a 4-8-week lead-in period, patients received topiramate in a 26-week open-label phase. Daily dose was increased from 25 mg to 100 mg in steps of 25 mg every week; the dose could be adjusted further in the range 50-200 mg/day, but was stable for the final 4 weeks. Patients were randomly assigned to continue this dose or switch to placebo for a 26-week double-blind phase. The primary endpoint was the difference in number of days with migraine during the last 4 weeks of the double-blind phase compared with the last 4 weeks of the open-label phase. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-000321-29. Findings 559 patients (68.3%) completed the open-label phase; 514 entered the double-blind phase and were assigned to topiramate (n=255) or placebo (n=259). The mean increase in number of migraine days was greater in the placebo group (1.19 days in 4 weeks, 95% CI 0.71 to 1.66; p < 0.0001) than in the topiramate group (0.10, -0.36 to 0.56; p=0.5756; mean difference between groups -1.09, -1.75 to -0.43). Patients in the placebo group had a greater number of days on acute medication than did those in the topiramate group (mean difference between groups -0.95, -1.49 to -0.41; p=0.0007). Quality of life, as assessed by the MIDAS questionnaire, fell in the placebo group but remained stable in the topiramate group. Patients were more satisfied with the efficacy of topiramate than with that of placebo, whereas satisfaction with tolerability was similar in both treatment groups. Interpretation Sustained benefit was reported after discontinuation of topiramate, although number of migraine days did increase. These findings suggest that patients should be treated for 6 months, with the option to continue to 12 months in some patients. [less ▲]Detailed reference viewed: 23 (4 ULg)