Novel Use of Ketotifen (Mast Cell Stablizier)in Fibromyalgia: A Pilot Study

酮替芬（肥大细胞稳定剂）在纤维肌痛中的新用途：初步研究

• 批准号: 8322817
• 负责人: Dennis Chua Ang
• 金额: $ 2.88万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8322817
• 关键词: Accounting; Affect; Biological Markers; Biopsy; Blood; CCL2 gene; Cells; Clinical Trials; Corticotropin-Releasing Hormone; Data; Development; Disease; Drug Delivery Systems; Economics; Eotaxin; FDA approved; Fibromyalgia; Foundations; Functional disorder; Health; Human; IL8 gene; Immune; Immunologics; Inflammation Mediators; Inflammatory; Interleukin-6; Intervention; Investigation; Knowledge; Literature; Mast Cell Stabilizer; Mediator of activation protein; Medical; Minority; Monitor; Neuraxis; Norepinephrine; Outcome; Outcome Assessment; Outcome Measure; Pain; Pain Threshold; Pathogenesis; Pathway interactions; Patients; Peripheral; Pharmaceutical Preparations; Phase; Physical Function; Pilot Projects; Placebo Effect; Placebos; Population; Production; Productivity; Randomized; Randomized Clinical Trials; Reporting; Research; Role; Running; Serotonin; Severities; Severity of illness; Skin; Societies; Source; Stimulus; Substance P; Symptoms; Testing; Therapeutic; Translating; Treatment Efficacy; Treatment outcome; Work; afferent nerve; base; bench to bedside; central sensitization; chemokine; chronic pain; cytokine; design; effective therapy; efficacy testing; hypothalamic-pituitary-adrenal axis; improved; inflammatory pain; inhibitor/antagonist; innovation; mast cell; mortality; novel; novel therapeutic intervention; pregabalin; pressure; randomized placebo controlled trial; reuptake; tool; treatment effect; treatment trial

DESCRIPTION (provided by applicant): Despite the enormous societal and personal burden of fibromyalgia (FM), effective treatment for this condition remains suboptimal. Only one-third of patients in clinical trials derive at least some benefit from currently FDA-approved drugs for FM. Poor treatment outcomes may be accounted for by the absence of drugs that target other aspects of the pathophysiology of FM. Increased number of skin mast cell, a powerful inflammatory cell, has been noted in FM skin biopsies. Mast cells mediators (e.g., chemokines) maybe a potential source of increased peripheral stimuli reaching the central nervous system that induce and/or maintain central sensitization. Interestingly, blood levels of chemokines (i.e., IL-8, MCP-1 and eotaxin) have been reported to be elevated in patients with FM. Despite growing evidence of the immunologic basis of FM however, drug trials have largely focused on centrally-acting agents that influence the ascending (e.g., pregabalin) or the descending (e.g., serotonin-norepinephrine reuptake inhibitors) pain pathways. Perhaps adjunctive therapies directed against inflammatory mediators or towards mast cells may improve the dismal treatment outcomes in FM. Therefore, we propose to conduct a randomized clinical trial using ketotifen (mast cell stabilizer) for FM, and to obtain preliminary estimates of treatment effects for use in designing a larger trial. After a one week placebo run-in phase, 38 FM patients will be randomized to receive ketotifen or placebo for 10 weeks. Outcome assessments at baseline (week 0) and week 11 will include the following: weekly average pain severity, chemokine levels (i.e., IL-8, MCP-1 and eotaxin) and pressure pain threshold. The proposed research is innovative because it will be the first to investigate the effects of an immune-based therapy on FM-related pain, and also the first to evaluate chemokines as biomarkers of disease severity.

描述(由申请人提供)：尽管纤维肌痛(FM)给社会和个人带来了巨大的负担，但这种疾病的有效治疗仍然不是最理想的。在临床试验中，只有三分之一的患者至少从FDA批准的FM药物中获得了一些好处。不良的治疗结果可能是由于缺乏针对FM病理生理学的其他方面的药物。皮肤肥大细胞，一种强大的炎性细胞，在FM皮肤活检中被注意到数量增加。肥大细胞介质(例如，趋化因子)可能是到达中枢神经系统的外周刺激增加的潜在来源，从而诱导和/或维持中枢敏化。有趣的是，据报道，FM患者血液中趋化因子(即IL-8、MCP-1和嗜酸性粒细胞趋化因子)水平升高。然而，尽管越来越多的证据表明FM的免疫学基础，药物试验主要集中在影响上行(如普瑞巴林)或下行(如5-羟色胺-去甲肾上腺素再摄取抑制剂)疼痛通路的中枢作用剂。也许针对炎症介质或肥大细胞的辅助治疗可以改善FM的黯淡治疗结果。因此，我们建议使用酮替芬(肥大细胞稳定剂)治疗FM进行随机临床试验，并获得治疗效果的初步估计，用于设计更大规模的试验。经过一周的安慰剂磨合阶段后，38名FM患者将随机接受酮替芬或安慰剂治疗10周。基线(第0周)和第11周的结果评估将包括以下内容：每周平均疼痛严重程度、趋化因子水平(即IL-8、MCP-1和嗜酸性粒细胞趋化因子)和压痛阈值。这项拟议的研究具有创新性，因为它将是第一次调查基于免疫的治疗对FM相关疼痛的影响，也是第一次评估趋化因子作为疾病严重程度的生物标志物。