Translational Trial of Propranolol & Rehabilitation for Treating Fibromyalgia

 描述(申请人提供)：在这份U34申请中，我们建议有一个2年的规划期，使我们能够准备进行一项临床研究，评估心得安用于增强激活康复治疗纤维肌痛综合征(FMS)的疗效。FMS是一种常见的慢性疼痛障碍，无法治愈。文献表明，没有一种单一的方法是普遍有效的，最好的证据建议使用多模式方法，包括激活运动、认知行为疗法和教育。此外，研究表明，FMS患者会经历肾上腺素能功能障碍，特别是对运动的反应，重新调节这一功能可能对成功的治疗非常重要。然而，运动后疼痛和疲劳，特别是延迟性肌肉酸痛(DOMS)在FMS中非常常见，这使得患者很难遵守康复方案。我们的初步工作提示：1)小剂量心得安有助于恢复FMS患者的肾上腺素能反应，2)小剂量心得安可减轻FMS患者的临床疼痛，3)激活康复可改善FMS症状，4)心得安可改善DOMS。此外，在我们之前关于感觉、肾上腺素和免疫基因表达的工作中，我们已经表明，FMS和健康人对运动的反应的这些表达谱有很大的不同。因此，我们假设心得安可能有助于FMS和DOMS的疼痛，从而增强康复努力的效果，其作用应反映在基因表达谱的变化上。在这项拟议的研究中，我们将招募200名有DOMS病史的FMS女性，她们将被随机分配到小剂量心得安康复治疗组和安慰剂组康复治疗组。我们将进行一系列的基因表达分析来跟踪这些变化。我们的目标是1)检测心得安对多模式康复治疗FMS益处的促进作用，以及2)评估和量化基因表达谱在心得安对FMS患者的反应和激活康复中的作用。在规划阶段，我们将1)进行可行性分析 对于患者招募，2)完善研究方案，3)制定招募战略，特别是增加来自少数族裔群体的参与者，4)制定操作程序手册和完成监管活动，5)开发数据库和完善分析程序，6)完善安全监测和建立外部安全监测委员会，7)为研究临床医生制定培训手册，8)准备U01申请。

 DESCRIPTION (provided by applicant): In this U34 application, we propose to have a 2 year planning period that will allow us to prepare for conducting a clinical study evaluating the efficacy of the use of propranolol for enhancing the benefit of activating rehabilitation for treatng fibromyalgia syndrome (FMS). FMS is a common chronic pain disorder with no cure. Literature indicates that no single modality is universally effective and the best evidence recommends the use of multimodal approach including activating exercise, cognitive behavioral therapy, and education. Furthermore, research has yielded that FMS patients experience adrenergic dysfunction, especially in response to exercise, and re-regulation of this may be very important for successful treatment. However, post exertion pain and fatigue, particularly delayed onset muscle soreness (DOMS), are very common in FMS, making it difficult for patients to comply with rehabilitative regimen. Our preliminary work suggests that 1) low dose propranolol helps restore the adrenergic response in FMS patients, 2) low dose propranolol reduces clinical pain in FMS patients, 3) activating rehabilitation can improve FMS symptoms, and 4) propranolol may improve DOMS. Furthermore, in our previous work with sensory, adrenergic and immune gene expression, we have shown that those expression profiles in response to exercise greatly differ between FMS and healthy people. Thus, we hypothesize that propranolol may help pain in FMS and DOMS, thereby enhancing the effect of rehabilitative effort, and the effects should be reflected in the changes in the gene expression profiles. In this proposed study, we will recruit 200 FMS women with a history of DOMS, who will be randomly assigned to either low dose propranolol with rehabilitation or placebo with rehabilitation. We will perform a series of gene expression analyses to track the changes. We aim to 1) examine the enhancing effect of propranolol on the benefit of multimodal rehabilitation for treating FMS, and 2) evaluate and quantify the role of the gene expression profiles in response to propranolol and activating rehabilitation for FMS patients. During the planning stage, we will 1) conduct feasibility analyses for patient recruitment, 2) refine the study protocol, 3) develop recruitment strategies particulary to increase participants from the ethnic minority groups, 4) develop the Manual of Operating Procedures and complete regulatory activities, 5) develop database and refinement of the analytical procedures, 6) refine the safety monitoring and establish an external safety monitoring board, 7) develop a training manual for study clinicians, and 8) prepare a U01 application.