Translational Trial of Propranolol & Rehabilitation for Treating Fibromyalgia

 描述（由申请人提供）：在本U34申请中，我们建议有2年的计划期，以便我们准备开展一项临床研究，评价普萘洛尔用于增强激活康复治疗纤维肌痛综合征（FMS）的获益的疗效。FMS是一种常见的慢性疼痛疾病，无法治愈。文献表明，没有单一的方式是普遍有效的，最好的证据建议使用多模式的方法，包括激活运动，认知行为治疗和教育。此外，研究表明，FMS患者经历肾上腺素能功能障碍，特别是对运动的反应，并且重新调节这一点对于成功治疗可能非常重要。然而，运动后疼痛和疲劳，特别是迟发性肌肉酸痛（DOMS），是非常常见的FMS，使患者难以遵守康复方案。我们的初步工作表明，1）低剂量普萘洛尔有助于恢复FMS患者的肾上腺素能反应，2）低剂量普萘洛尔减轻FMS患者的临床疼痛，3）激活康复可以改善FMS症状，4）普萘洛尔可以改善DOMS。此外，在我们以前的工作与感觉，肾上腺素能和免疫基因表达，我们已经表明，这些表达谱响应运动之间FMS和健康人有很大的不同。因此，我们假设普萘洛尔可能有助于FMS和DOMS的疼痛，从而增强康复努力的效果，其效果应反映在基因表达谱的变化中。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低剂量普萘洛尔与康复治疗组或安慰剂与康复治疗组。我们将进行一系列的基因表达分析来跟踪这些变化。我们的目的是1）检查普萘洛尔对治疗FMS的多模式康复的益处的增强作用，以及2）评估和量化基因表达谱在普萘洛尔应答和激活FMS患者康复中的作用。在规划阶段，我们会：1）进行可行性分析 患者招募，2）完善研究方案，3）制定招募策略，特别是增加少数民族受试者，4）制定操作程序手册并完成监管活动，5）开发数据库并完善分析程序，6）完善安全性监测并建立外部安全性监测委员会，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.