Translational Trial of Propranolol & Rehabilitation for Treating Fibromyalgia

普萘洛尔的转化试验

• 批准号: 9130756
• 负责人: Akiko Okifuji
• 金额: $ 32.78万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9130756
• 关键词: Acute; Address; Adrenal Glands; Adrenergic Agents; Adrenergic beta-Antagonists; Affect; Anxiety; Cell Respiration; Chronic; Clinical; Clinical Research; Clinical Trials; Clinical Trials Data Monitoring Committees; Cognitive Therapy; Combined Modality Therapy; Data; Databases; Development; Dose; Double-Blind Method; Drops; Education; Etiology; Exercise; Exercise stress test; Exertion; Fatigue; Fibromyalgia; Flare; Functional disorder; Gene Expression; Genes; Health; Hour; Hypothalamic structure; Immune; Literature; Manuals; Measurement; Mediating; Minority Groups; Modality; Modeling; Molecular; Molecular Profiling; Monitor; Muscle; Pain; Pain Disorder; Participant; Patient Recruitments; Patients; Performance; Persistent pain; Physiological; Pituitary Gland; Placebos; Population; Preparation; Procedures; Propranolol; Protocols documentation; Public Health; Randomized; Randomized Controlled Trials; Recording of previous events; Recruitment Activity; Regimen; Regulation; Rehabilitation therapy; Research; Rheumatism; Role; Safety; Sensory; Series; Societies; Staging; Symptoms; Testing; Therapeutic; Therapeutic Effect; Time; Training; Translational trial; Woman; Work; beta-adrenergic receptor; central sensitization; chronic pain; cost; efficacy testing; ethnic minority population; exercise intensity; exercise intolerance; experience; fibromyalgia pain; immune activation; improved; pain symptom; programs; response; success

 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.

 描述（由申请人提供）：在此 U34 申请中，我们建议有 2 年的规划期，这将使我们能够准备开展一项临床研究，评估使用普萘洛尔的功效，以增强激活康复治疗纤维肌痛综合征 (FMS) 的益处。 FMS 是一种常见的慢性疼痛疾病，无法治愈。文献表明，没有一种单一方式是普遍有效的，最好的证据建议使用多方式方法，包括激活运动、认知行为治疗和教育。此外，研究表明，FMS 患者会出现肾上腺素能功能障碍，尤其是对运动的反应，对此进行重新调节可能对于成功治疗非常重要。然而，劳累后疼痛和疲劳，特别是迟发性肌肉酸痛（DOMS）在FMS中非常常见，使得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）低剂量普萘洛尔可减轻 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，在我们之前对感觉、肾上腺素和免疫基因表达的研究中，我们已经表明，FMS 和健康人之间对运动的反应的表达谱有很大差异。因此，我们推测普萘洛尔可能有助于缓解 FMS 和 DOMS 的疼痛，从而增强康复努力的效果，并且这种效果应该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，她们将被随机分配接受低剂量普萘洛尔康复治疗或安慰剂康复治疗。我们将进行一系列基因表达分析来跟踪变化。我们的目标是 1) 检查普萘洛尔对治疗 FMS 的多模式康复益处的增强作用，以及 2) 评估和量化基因表达谱对普萘洛尔的反应和激活 FMS 患者康复的作用。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）制定招募策略，特别是增加少数民族参与者，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）完善安全监测并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。