Abstract：
BACKGROUND: Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia.
METHODS: This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels).
BACKGROUND: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen\'s University Health Sciences Research Ethics Board (Queen\'s HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings.
BACKGROUND: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.
METHODS: This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels).
BACKGROUND: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen\'s University Health Sciences Research Ethics Board (Queen\'s HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings.
BACKGROUND: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.
摘要：
背景：纤维肌痛与慢性广泛性疼痛和睡眠障碍有关。多学科,多模式管理通常包括药物治疗；然而，目前用于治疗纤维肌痛的药物仅对30-60%的治疗个体提供有意义的益处.两种或两种以上不同药物的组合在临床实践中很常见，期望获得更好的疗效。耐受性或两者兼而有之；然而，需要进一步的研究来确定哪些组合实际上提供了额外的好处。因此，我们正在计划一项临床试验,以评估褪黑素(MLT)-普瑞巴林(PGB)联合应用于纤维肌痛患者.
方法：这将是一个单中心，双盲,随机化，双假人,三个时期，交叉试验比较MLT-PGB组合与每种单药治疗的54名符合2016年美国风湿病学会纤维肌痛标准的成年参与者.参与者将获得最大耐受剂量的MLT，PGB和MLT-PGB结合6周。主要结果将是每日疼痛强度（0-10）;次要结果将包括纤维肌痛影响问卷，SF-36调查，医学结果研究睡眠量表，贝克抑郁量表(BDI-II)，不良事件和其他措施。主要和次要结果的分析将涉及具有序列的线性混合模型，period,治疗,一阶保留和基线疼痛评分作为固定效应，参与者作为随机效应，以测试三种治疗方法之间是否存在任何治疗差异，并估计每种治疗方法的平均每日疼痛强度的最小二乘平均值。调整结转和时期效应(即，疼痛水平的稳定性)。
背景：本试验已在国际标准随机对照试验编号登记处注册，ISRCTN#18278231已获得女王大学健康科学研究伦理委员会（女王HSREB协议#6040998）的伦理批准，目前正在审查加拿大卫生部天然和非处方健康产品局的临床试验申请。所有参与者将在试验参与前提供书面知情同意书。试验完成后，结果将在一个或多个生物医学杂志出版物中传播，并在一个或多个科学会议上发表。
背景：本试验已在国际标准随机对照试验编号登记处注册，ISRCTN18278231。
方法：这将是一个单中心，双盲,随机化，双假人,三个时期，交叉试验比较MLT-PGB组合与每种单药治疗的54名符合2016年美国风湿病学会纤维肌痛标准的成年参与者.参与者将获得最大耐受剂量的MLT，PGB和MLT-PGB结合6周。主要结果将是每日疼痛强度（0-10）;次要结果将包括纤维肌痛影响问卷，SF-36调查，医学结果研究睡眠量表，贝克抑郁量表(BDI-II)，不良事件和其他措施。主要和次要结果的分析将涉及具有序列的线性混合模型，period,治疗,一阶保留和基线疼痛评分作为固定效应，参与者作为随机效应，以测试三种治疗方法之间是否存在任何治疗差异，并估计每种治疗方法的平均每日疼痛强度的最小二乘平均值。调整结转和时期效应(即，疼痛水平的稳定性)。
背景：本试验已在国际标准随机对照试验编号登记处注册，ISRCTN#18278231已获得女王大学健康科学研究伦理委员会（女王HSREB协议#6040998）的伦理批准，目前正在审查加拿大卫生部天然和非处方健康产品局的临床试验申请。所有参与者将在试验参与前提供书面知情同意书。试验完成后，结果将在一个或多个生物医学杂志出版物中传播，并在一个或多个科学会议上发表。
背景：本试验已在国际标准随机对照试验编号登记处注册，ISRCTN18278231。
