Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial
Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial
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DOI：
10.1016/s1474-4422(18)30203-5
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发表时间：
2018-08-01
期刊：
影响因子：
48
通讯作者：
van Engelen, Baziel G. M.
中科院分区：
文献类型：
--
作者：
Okkersen, Kees;Jimenez-Moreno, Cecilia;van Engelen, Baziel G. M.
背景强直性肌营养不良1型是成人肌营养不良症中最常见的形式，导致严重的疲劳，严重的身体功能障碍，并限制社会参与。在这项研究中，我们的目的是确定与单独的标准治疗相比，认知行为治疗与分级运动相结合是否能改善强直性肌营养不良1型患者的健康状况。方法我们在巴黎（法国）、慕尼黑（德国）、奈梅亨（荷兰）和纽卡斯尔（英国）。符合条件的参与者是年龄在18岁及以上的患者，确诊为强直性肌营养不良1型，他们严重疲劳（即，检查表上的得分>= 35-个体力量，子量表疲劳）。我们将参与者（1：1）随机分配到认知行为疗法加标准护理和可选的分级运动或仅标准护理。通过基于网络的中央系统进行随机化，并按研究中心分层。认知行为疗法的重点是解决患者主动性降低，增加体力活动，优化社会互动，调节睡眠-觉醒模式，应对疼痛，并解决有关疲劳和强直性肌营养不良1型的信念。认知行为疗法在10-14个疗程中进行了10个月的治疗。在奈梅亨和纽卡斯尔，可以在认知行为疗法中加入一个分级运动模块。主要结局是DM 1-Activ-c量表评分较基线的10个月变化，该量表是活动和社会参与能力的衡量指标（评分范围0-100）。主要结局的统计分析包括所有数据可用的参与者，使用混合效应线性回归模型，基线评分作为协变量。安全性数据以连续性表示。该试验注册于ClinicalTrials.gov，编号NCT 02118779。结果在2014年4月2日至2015年5月29日期间，我们随机分配了255名患者接受治疗：128名接受认知行为治疗加标准治疗，127名接受标准治疗。在128名被分配接受认知行为治疗的患者中，有33名（26%）还接受了分级运动模块。随访持续至2016年10月17日。DM 1-Activ-c评分从平均（SD）61.22从基线时的（17.35）分降至63.92分（17.41）认知行为治疗组第10个月（校正的平均差异为1.53，95% CI -0.14至3.20），从63.00（17.35）至60.79（18.49），标准治疗组（-2.02，-4.02至-0.01），组间平均差异为3.27分（95% CI 0.93至5.62，p=0.007）。认知行为治疗组65例（51%）患者发生244起不良事件，标准治疗组63例（50%）患者发生155起不良事件，其中最常见的是福尔斯（认知行为治疗组40例（31%）患者发生155起事件，标准治疗组33例（26%）患者发生71起事件）。24例严重不良事件记录在19（15%）患者的认知行为治疗组和23例（12%）患者的标准治疗组，其中最常见的是胃肠道和cardiac.Interpretation认知行为治疗增加了活动能力和社会参与的1型肌强直性营养不良症患者在10个月。由于没有治愈性治疗和很少的对症治疗，认知行为疗法可以考虑用于严重疲劳的1型强直性肌营养不良患者。版权所有（C）2018 Elsevier Ltd.保留所有权利。
Background Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1.Methods We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of >= 35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep-wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10-14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0-100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered with ClinicalTrials.gov, number NCT02118779.Findings Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 to cognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1-Activ-c score increased from a mean (SD) of 61.22 (17.35) points at baseline to 63.92 (17.41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1.53, 95% CI -0.14 to 3.20), and decreased from 63.00 (17.35) to 60.79 (18.49) in the standard care group (-2.02, -4.02 to -0.01), with a mean difference between groups of 3.27 points (95% CI 0.93 to 5.62, p=0.007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac.Interpretation Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1. Copyright (C) 2018 Elsevier Ltd. All rights reserved.