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首页> 外文期刊>The journal of clinical hypertension. >Dietary Sodium: A Perspective on Recent Sodium Evidence-Its Interpretation and Controversies
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Dietary Sodium: A Perspective on Recent Sodium Evidence-Its Interpretation and Controversies

机译：膳食钠：近期钠证据的观点及其解释和争议

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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.
机译：背景：发作性睡病的特征是白天过度嗜睡（EDS）和瘫痪。组胺神经元对于保持清醒至关重要。我们评估了发作性睡病患者中pitolisant（以前称为BF2.649）的安全性和有效性，pitolisant是一种选择性的组胺H3受体反向激动剂，可激活这些神经元。方法：对于这项双盲，随机，平行分组对照试验，我们从欧洲五个国家的32个睡眠障碍中心招募了发作性睡病患者。如果患者年龄在18岁或18岁以上，未服用精神刺激药至少14天且具有EDS（定义为Epworth嗜睡量表[ESS]得分至少14），则符合条件。使用计算机生成的随机序列，我们随机分配患者接受pitolisant，莫达非尼或安慰剂（1：1：1）。治疗持续8周：根据研究者的判断，连续3周（每天10 mg，20 mg或40 mg pitolisant的剂量; 100 mg，200 mg或400 mg莫达非尼的剂量），然后连续5周稳定剂量。病人每天服用四片双假药以确保掩盖。对于在意向性治疗人群中评估的主要分析，我们评估了pitolisant相对于安慰剂的优越性，以及pitolisant相对于莫达非尼的非劣效性。该试验已在ClinicalTrials.gov上注册，编号为NCT01067222。研究结果：在2009年5月26日至2010年6月30日之间，我们筛选了110例患者，其中95例符合条件并随机分配治疗：安慰剂30例，皮托利松32例，莫达非尼33例。在8周的治疗期内，安慰剂组的ESS评分平均降低为-3·4（SD 4·2），皮立舒通组的-5·8（6·2）和-6·9（6· 2）在莫达非尼组中。我们对终点的ESS平均得分之间的组间差异的初步分析（针对基线进行了调整）显示，匹立莫桑优于安慰剂（差异-3·0，95％CI -5·6至-0·4; p = 0· 024），但不低于莫达非尼（差异0·12，95％CI -2·5至2·7; p = 0·250）。我们记录了22例pitolisant不良事件，26例莫达非尼和安慰剂10例不良事件。六个严重的不良事件与治疗有关：一个伴有垂体疏松（腹部不适），另外五个伴有莫达非尼（腹部疼痛，异常行为，苯丙胺样戒断症状，​​淋巴结肿大和内耳疾病）。解释：与安慰剂相比，剂量高达40 mg的Pitolisant对EDS有效，与莫达非尼相比耐受性良好。如果这些发现在进一步的研究中得到证实，那么pitolisant可以为发作性睡病患者提供新的治疗选择。资金来源：法国Bioprojet。

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