Combined Behavioral & Analgesic Trial for Fibromyalgia (COMBAT-FM)

描述（由申请人提供）：纤维肌痛（FM）是一种慢性广泛疼痛综合征，具有许多并发症状（例如，睡眠困难，疲劳，抑郁，焦虑），发病机制未知，没有良好复制的生物标志物，估计在美国影响3-6百万人口。FM患者报告的症状多样性与FM是一种多系统疾病的观点是一致的，涉及生物、心理和社会机制的复杂相互作用。虽然一些药理学的评估显示出有益的效果，但没有一个是治愈的。这些治疗减少了大约35%的疼痛，但不超过一半的患者有临床意义的改善。非药物治疗也报告了类似的结果，特别是认知行为疗法（CBT），在减轻疼痛和改善功能方面，它已被证明能产生与药物相同的效果。这些单一疗法的适度效果已经引起了对药物和非药物治疗联合试验的呼吁。目前还没有研究像美国疼痛协会建议的那样评估CBT和药物联合治疗的增量益处。拟议研究的一个主要目的是评估CBT的改良版本，CBTfm，针对疲劳，睡眠，疼痛，抑郁和焦虑和曲马多的组合，曲马多是一种具有镇痛，抗血清素能特性的药物，并抑制神经对去甲肾上腺素的再摄取。根据已发表的文献和循证临床实践指南，我们假设CBTfm+曲马多联合治疗的改善效果明显大于健康教育+曲马多、健康教育+安慰剂或CBTfm+安慰剂。第二个目标是使用活动描记术（一种对睡眠和活动的客观测量方法）来评估患者对睡眠质量和活动的感知与这两个关键变量的客观指标之间的“知觉分离”。有证据表明，FM患者避免活动不仅是因为当前的疲惫，还因为他们认为如果他们活动会加重疲劳和疼痛，我们假设患者的感知与睡眠和活动的客观指标之间存在弱关系。FM治疗对FM有效的机制尚不清楚。第三个目标是评估心理和神经生理变量作为结果的潜在介质。最后，第四个目标是测试疲劳对FM中由疼痛、睡眠和情绪障碍引起的活动水平的中介效应模型。这些结果将对制定FM的最佳治疗方案、了解治疗结果的机制以及这种普遍疼痛状况下睡眠、疲劳、活动、疼痛和情绪之间的关联具有重要意义。

DESCRIPTION (provided by applicant): Fibromyalgia (FM) is a chronic widespread pain syndrome with a number of concurrent symptoms (e.g., sleep difficulties, fatigue, depression, anxiety), unknown pathogenesis, and no well-replicated biological markers that is estimated to affect 3-6 million people in the United States. The diversity of symptoms reported by FM patients is consistent with the view that FM is a multisystem disorder, involving a complex interaction of biological, psychological, and social mechanisms. Although evaluations of a number pharmacological have shown beneficial effects none are curative. These treatments reduce pain by approximately 35% but no more than half of patients experience clinically meaningful improvements. Similar outcomes have been reported by nonpharmacological treatments, particularly cognitive-behavior therapy (CBT), which has been shown to produce equivalent benefits to medication in reducing pain and improving function. The modest outcomes of these montherapies have led to calls for combination trials of drugs and nondrug treatments. No studies have evaluated the incremental benefits of combining CBT and medication as suggested in the American Pain Society. A primary objective of the proposed research is to evaluate the combination of a modified version of CBT, CBTfm that targets fatigue, sleep, pain, depression, and anxiety and tramadol, a medication that has analgesic, antiserotonergic properties, and inhibits the neuronal reuptake of norepinephrine for FM. Based on published literature and evidence-based clinical practice guideline, we hypothesize that the combination of CBTfm+Tramadol will lead to significantly greater improvement than Health Education + Tramadol, Health Education + Placebo, or CBTfm +Placebo. A second objective is to use actigraphy, an objective measure of sleep and activity, to evaluate the "perceptual dissociation" between patients' perceptions of their sleep quality and activity and objective indices of these two key variables. Based on evidence that FM patients avoid activity not only because of current exhaustion but also because of believe that fatigue and pain will worsen if they are active, we hypothesize that there will be a weak relationship between patients' perceptions and the objective indices of sleep and activity. The mechanisms by which treatments for FM are effective for FM are unknown. A 3rd objective is to evaluate psychological and neurophysiological variables as potential mediators of outcome. Finally, the 4th objective is to test a model of the mediational effects of fatigue on activity level, arising from pain, sleep and mood disturbance in FM. The results will have important implications for developing optimal treatment programs for FM, the mechanisms understanding treatment outcome, and the associations among sleep, fatigue, activity, pain, and mood in this prevalent pain condition.