Department of Human Genetics, Centre Hospitalier Universitaire de Quebec, Quebec City, Canada.
Clin Ther. 2012 May;34(5):1103-11. doi: 10.1016/j.clinthera.2012.03.060.
Despite the fact that excessive daytime sleepiness (EDS) is one of the most common manifestations in patients with myotonic dystrophy type 1 (DM1), no treatment is yet available. Methylphenidate is being studied for prospective use in the treatment of EDS.
The aim of this investigator-initiated study was to evaluate the efficacy and tolerability of a single 20-mg morning dose of methylphenidate for the treatment of EDS in adults with DM1.
This randomized, double-blind, placebo-controlled, 3-week crossover trial was conducted at 2 sites in Quebec. French-Canadian patients with DM1 with an Epworth Sleepiness Scale score ≥10 were invited to participate in this crossover trial of 20 mg/d of methylphenidate versus placebo, with 3 weeks in each arm of the study separated by a 2-week washout period. The primary efficacy end points were the Daytime Sleepiness Scale and the Epworth Sleepiness Scale at week 3. Secondary end points included the energy/vitality scale of the RAND 36-Item Health Survey, the Profile of Mood States questionnaire, and the mean sleep latency test. Assessment of tolerability profile included a physical examination, measurement of blood pressure, standard 12-lead ECG, and laboratory tests. Adverse event assessments were recorded based on patient reporting at each visit on clinical report forms.
In a total of 24 patients (12 men, 12 women; mean [SD] age, 46 [13] years), 17 completed the study. Treatment with methylphenidate showed a significant change in median scores on the Daytime Sleepiness Scale (-3.0 vs -0.5; P = 0.003) and the Epworth Sleepiness Scale (-3.0 vs -1.5; P = 0.039). The Profile of Mood States and the energy/vitality scale from the RAND 36-Item Health Survey showed no significant changes. Likewise, there was no significant change in mean sleep latency test results. One patient died during the trial, but the autopsy results eliminated methylphenidate as cause of death. Three patients discontinued methylphenidate due to treatment-emergent adverse events (1, diarrhea; 2, nervousness and irritability). Loss of appetite, nausea, and palpitations were the most common adverse events reported by more patients treated with methylphenidate than those receiving placebo.
A single 20-mg dose of methylphenidate significantly reduced daytime sleepiness in this small selected population of patients with DM1. ClinicalTrials.gov identifier: NCT01421992.
尽管日间嗜睡（EDS）是肌强直性营养不良 1 型（DM1）患者最常见的表现之一，但目前尚无治疗方法。哌醋甲酯正被研究用于治疗 EDS。
本研究旨在评估 20mg 单剂量哌醋甲酯治疗 DM1 成人 EDS 的疗效和耐受性。
这是一项在魁北克的 2 个地点进行的、由研究者发起的、随机、双盲、安慰剂对照、3 周交叉试验。被邀请参加这项 20mg/d 哌醋甲酯与安慰剂交叉试验的是患有 DM1、Epworth 嗜睡量表评分≥10 的法裔加拿大患者，每 3 周为一个研究臂，每个臂之间有 2 周的洗脱期。主要疗效终点为第 3 周的日间嗜睡量表和 Epworth 嗜睡量表。次要终点包括 RAND 36 项健康调查的能量/活力量表、心境状态问卷和平均睡眠潜伏期测试。耐受性评估包括体格检查、血压测量、标准 12 导联心电图和实验室检查。根据临床报告表上的患者报告，记录不良事件评估。
共有 24 名患者（12 名男性，12 名女性；平均[标准差]年龄，46[13]岁）完成了研究。哌醋甲酯治疗组日间嗜睡量表（-3.0 与-0.5；P=0.003）和 Epworth 嗜睡量表（-3.0 与-1.5；P=0.039）的中位数评分有显著变化。RAND 36 项健康调查的心境状态问卷和能量/活力量表没有显著变化。同样，平均睡眠潜伏期测试结果也没有显著变化。一名患者在试验期间死亡，但尸检结果排除了哌醋甲酯是死亡原因。由于治疗引起的不良事件，有 3 名患者停止使用哌醋甲酯（1 名，腹泻；2 名，紧张和易怒）。与服用安慰剂的患者相比，更多服用哌醋甲酯的患者报告了食欲不振、恶心和心悸等常见的不良事件。
在这个患有 DM1 的小选择人群中，单剂量 20mg 哌醋甲酯显著降低了白天的嗜睡程度。临床试验注册号：NCT01421992。
