Dauvilliers Y.,Montpellier University |
Bassetti C.,University of Bern |
Lammers G.J.,Leiden University |
Arnulf I.,Sleep Disorder Unit |
And 6 more authors.
The Lancet Neurology | Year: 2013
Background: Narcolepsy is characterised by excessive daytime sleepiness (EDS) and cataplexy. Histamine neurons are crucial to maintain wakefulness. We assessed the safety and efficacy of pitolisant (previously called BF2.649), a selective histamine H3 receptor inverse agonist that activates these neurons, in patients with narcolepsy. Methods: For this double-blind, randomised, parallel-group controlled trial, we recruited patients with narcolepsy from 32 sleep disorder centres in five European countries. Patients were eligible if they were aged 18 years or older, had not taken psychostimulants for at least 14 days, and had EDS (defined as an Epworth Sleepiness Scale [ESS] score of at least 14). Using a computer-generated randomisation sequence, we randomly allocated patients to receive pitolisant, modafinil, or placebo (1:1:1). Treatment lasted 8 weeks: 3 weeks of flexible dosing according to investigator's judgment (10 mg, 20 mg, or 40 mg a day of pitolisant; 100 mg, 200 mg or 400 mg a day of modafinil) followed by 5 weeks of stable dosing. Patients took four tablets a day in a double-dummy design to ensure masking. For the primary analysis, assessed in the intention-to-treat population, we assessed the superiority of pitolisant versus placebo, and the non-inferiority of pitolisant versus modafinil. This trial is registered with ClinicalTrials.gov, number NCT01067222. Findings: Between May 26, 2009, and June 30, 2010, we screened 110 patients, 95 of whom were eligible and randomly assigned to treatment: 30 to placebo, 32 to pitolisant, and 33 to modafinil. Over the 8-week treatment period, mean ESS score reductions were -3·4 (SD 4·2) in the placebo group, -5·8 (6·2) in the pitolisant group, and -6·9 (6·2) in the modafinil group. Our primary analysis of between-group differences in mean ESS score at endpoint (adjusted for baseline) showed pitolisant to be superior to placebo (difference -3·0, 95% CI -5·6 to -0·4; p=0·024), but not non-inferior to modafinil (difference 0·12, 95% CI -2·5 to 2·7; p=0·250). We recorded 22 adverse events with pitolisant, 26 with modafinil, and ten with placebo. Six severe adverse events were treatment-related: one with pitolisant (abdominal discomfort) and five with modafinil (abdominal pain, abnormal behaviour, amphetamine-like withdrawal symptoms, lymphoadenopathy, and inner ear disorders). Interpretation: Pitolisant at doses up to 40 mg was efficacious on EDS compared with placebo and well tolerated compared with modafinil. If these findings are substantiated in further studies, pitolisant could offer a new treatment option for patients with narcolepsy. Funding: Bioprojet, France. © 2013 Elsevier Ltd. Source
Petit E.,University of Franche Comte |
Mougin F.,University of Franche Comte |
Bourdin H.,EA 481 |
Bourdin H.,Sleep Disorder Unit |
And 3 more authors.
European Journal of Applied Physiology | Year: 2014
Purpose: The aim of the study was to examine the effects of a post-prandial 20 min nap on a short-term physical exercise and subsequent sleep in athletes keeping their usual sleep schedules and in 5-h phase-advance condition. Methods: Sixteen healthy young male athletes (age 22.2 ± 1.7 years, non-habitual nappers) participated in the study. After a baseline 8-h time in bed in normal and 5-h advanced sleep schedules, a standardized morning and lunch in a laboratory environment, subjects underwent either a nap (20 min of sleep elapsed from 3 epochs of stage 1 or 1 epoch of stage 2), or a rest without sleep by lying in a bed, between 13:00 and 14:00 hours in non-shifted condition or 08:00 and 09:00 hours in shifted condition, after which anaerobic exercises were performed twice 2 h apart. Core body temperature was recorded throughout the study period. Results: The nap extended sleep onset latency from 6.72 ± 3.83 to 11.84 ± 13.44 min, after shifted condition but did not modify sleep architecture of the post-trial night among athletes, whether shifted or not. Moreover, napping did not improve physical performance but it delayed acrophase and batyphase of core body temperature rhythm parameters. Conclusion: Napping showed no reliable benefit on short-term performances of athletes exercising at local time or after a simulated jet lag. © 2013 Springer-Verlag Berlin Heidelberg. Source
Dauvilliers Y.,Sleep Disorder Center |
Dauvilliers Y.,Sleep Disorders Center |
Arnulf I.,National Ref. Netwk. for Orphan Dis. Narcol. |
Arnulf I.,Sleep Disorder Unit |
And 21 more authors.
Brain | Year: 2013
An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects aged <18 years, and 4.7 (1.6-13.9) in those aged 18 and over. Sensitivity analyses considering date of referral for diagnosis or the date of onset of symptoms as the index date gave similar results, as did analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n = 32; mostly AS03-adjuvanted vaccine, n = 28) to non-exposed cases (n = 30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In this sub-analysis, H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association cannot be completely ruled out, the associations appeared robust to sensitivity analyses, and a specific analysis focusing on ASO3-adjuvanted vaccine found similar increase. © The Author (2013). Source
Arnulf I.,Paris-Sorbonne University |
Arnulf I.,Sleep Disorder Unit |
Arnulf I.,University Pierre and Marie Curie |
Grosliere L.,Paris-Sorbonne University |
And 7 more authors.
Consciousness and Cognition | Year: 2014
We tested whether dreams can anticipate a stressful exam and how failure/success in dreams affect next-day performance. We collected information on students' dreams during the night preceding the medical school entrance exam. Demographic, academic, sleep and dream characteristics were compared to the students' grades on the exam. Of the 719 respondents to the questionnaire (of 2324 total students), 60.4% dreamt of the exam during the night preceding it. Problems with the exam appeared in 78% of dreams and primarily involved being late and forgetting answers. Reporting a dream about the exam on the pre-exam night was associated with better performance on the exam (p= .01). The frequency of dreams concerning the exam during the first term predicted proportionally higher performance on the exam (R= 0.1, p= .01). These results suggest that the negative anticipation of a stressful event in dreams is common and that this episodic simulation provides a cognitive gain. © 2014 Elsevier Inc. Source
Karroum E.G.,Sleep Disorder Unit |
Karroum E.G.,University Pierre and Marie Curie |
Golmard J.-L.,University Pierre and Marie Curie |
Leu-Semenescu S.,Sleep Disorder Unit |
And 3 more authors.
Clinical Journal of Pain | Year: 2015
Objectives: Limb sensations in restless legs syndrome (RLS) include an urge to move, a discomfort, or even a frank pain. However, no large studies compared painful to nonpainful RLS as specific phenotypes. We investigated the painful form of RLS in a clinical series of primary RLS patients and a large sample of members of the French RLS association (AFE). Materials and Methods: Fifty-six patients with primary RLS (face-to-face interviewed) and 734 AFE members (received by ground mail an self-report questionnaire) responded to the presence/absence of painful RLS sensations and were included. They completed a French reconstruction of the McGill Pain Questionnaire (Questionnaire Douleur de Saint-Antoine [QDSA]) to assess their RLS sensations as well as questions about demographics and clinical RLS features. Results: Sixty-one percent of interviewed patients and 55% of AFE members had painful RLS sensations. The patients with painful RLS were more sleepy and tired than those with nonpainful sensations. The RLS severity and need for current, dopaminergic treatment were higher in AFE members with painful than with nonpainful RLS. In both the groups, the QDSA qualifier "burning" was the most frequent (37% to 44%) sensory discriminator of painful RLS. In the AFE sample, QDSA scores, and the distribution of words in all QDSA subclasses was skewed toward a more severe connotation with more than one third of patients selecting affective discriminating words like "exasperating," "exhausting," and "unbearable." Discussion: Painful RLS appears to be a severe, "burning" subtype of RLS, and could be a distinct disease or a clinical variant in a sensations continuum. © 2014 Wolters Kluwer Health, Inc. Source