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

描述(申请人提供)：纤维肌痛(FM)是一种慢性广泛性疼痛综合征，具有许多并发症状(例如，睡眠困难、疲劳、抑郁、焦虑)，发病机制不明，并且没有良好复制的生物标志物，估计在美国影响300-600万人。FM患者报告的症状的多样性与FM是一种多系统障碍的观点是一致的，涉及生物、心理和社会机制的复杂相互作用。尽管对一些药理作用的评估显示了有益的效果，但没有一种是治愈的。这些治疗减少了大约35%的疼痛，但只有不超过一半的患者体验到了临床上有意义的改善。据报道，非药物治疗也有类似的结果，特别是认知行为治疗(CBT)，它在减轻疼痛和改善功能方面与药物产生了同等的好处。这些单一疗法的温和结果导致了对药物和非药物治疗进行联合试验的呼声。根据美国疼痛学会的建议，还没有研究评估CBT和药物联合治疗的增量益处。拟议研究的一个主要目标是评估针对疲劳、睡眠、疼痛、抑郁和焦虑的CBT的改良版本CBTfm与曲马多的组合，曲马多是一种具有止痛、抗5-羟色胺能特性并抑制FM神经元重新摄取去甲肾上腺素的药物。根据已发表的文献和循证临床实践指南，我们假设CBTfm+曲马多的联合治疗效果明显优于健康教育+曲马多、健康教育+安慰剂或CBTfm+安慰剂。第二个目标是使用动作图，一种衡量睡眠和活动的客观指标，来评估患者对其睡眠质量和活动的感知与这两个关键变量的客观指数之间的“感知分离”。根据FM患者避免活动的证据，不仅因为目前的疲惫，而且因为相信如果他们活动，疲劳和疼痛会恶化，我们假设患者的感知与睡眠和活动的客观指数之间将存在弱关系。治疗FM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学变量作为结果的潜在中介。最后，第四个目标是测试疲劳对FM中疼痛、睡眠和情绪障碍引起的活动水平的中介效应的模型。这些结果将对开发FM的最佳治疗方案、了解治疗结果的机制以及在这种普遍存在的疼痛情况下睡眠、疲劳、活动、疼痛和情绪之间的关系具有重要意义。 公共卫生相关性：拟议的研究涉及纤维肌痛(FM)的治疗，这是一种普遍存在的综合征，估计影响3至5名美国传教士。FM的特征是广泛的疼痛、疲劳、睡眠障碍、认知症状、抑郁、焦虑等症状。由于这些人口广泛使用卫生服务，FM可能会导致严重的残疾、复杂的管理决策和社会经济负担。目前还没有治愈FM的方法，现有的治疗方法只能在少数患者中减少大约35%的症状。这导致了将药理学和非药理学相结合的治疗方法的呼声。该项目将评估基于有前景的单独治疗的联合治疗的效果，即认知行为治疗和曲马多。这两种治疗方法都已被循证临床实践指南推荐为FM综合治疗方法的组成部分。这种结合有可能最大限度地发挥每个单独治疗的好处，减少痛苦，改善FM患者与健康相关的生活质量。

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. PUBLIC HEALTH RELEVANCE: The proposed research addresses treatment of fibromyalgia (FM), a prevalent syndrome that is estimated to affect 3 to 5 mission Americans. FM is characterized by widespread pain, fatigue, sleep disturbance, cognitive symptoms, depression, anxiety, among other symptoms. FM can lead to significant disability, complex management decision, and economic burden on society given this population's extensive use of health services. There is currently no cure for FM and available treatments only reduce symptoms by approximately 35% and in a minority of patients. This has led to calls for treatments that combine both pharmacological and nonpharmacological modalities. This project will evaluate the effects of a combination treatment based on promising individual treatments, namely, cognitive-behavior therapy and tramadol. Both of these treatments have been recommend as components of a comprehensive treatment approach to FM by evidence-based clinical practice guidelines. The combination has the potential to maximize the benefits of each individual treatment and to reduce suffering and improve the health-related quality of life for those with FM.