A CLINICAL TRIAL OF MYCOPHENOLATE MOFETIL IN MYASTHENIA GRAVIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目的：本研究的目的是验证MM(2.5g/d)联合泼尼松(20 mg/d)在MG的初始治疗中比单用强的松能更好地控制肌无力体征和症状的假设。开放标签的扩展将提供有关MM的安全性和耐受性的进一步信息，剂量在2.5克/天到3克/天之间，并将提供关于MM患者逐渐减少和停止使用强的松的初步信息。研究计划：这是一项随机、双盲、安慰剂对照、多中心的MM试验，在MG不严重的患者中使用中等剂量的强的松。双盲治疗是三(3)个月，然后是6个月的开放晚期。预计多中心登记的患者为80人。方法：受试者随机分为泼尼松20 mg/d、安慰剂或MM 2.5g/d，进行血常规和日常生活能力问卷调查，以确保安全性和初步改善。安全性评估和疾病严重程度评估将在研究用药4、8和12周后进行。开放式标签将在第13、14、15、16、20、28和36周继续进行安全评估和评估。临床意义：MG是一种不常见的自身免疫性疾病，在美国影响着大约50,000名患者，其中抗乙酰胆碱受体的抗体会导致神经肌肉传递失败、病理性疲劳和虚弱。大多数MG患者都使用免疫抑制药物，但目前的治疗方法并不统一有效，而且存在严重副作用的风险。初步报道表明，霉酚酸酯(MM)是一种用于预防同种异体移植排斥反应的T和B细胞的选择性抑制剂，在MG中是有效的，且耐受性良好。与目前使用的非类固醇药物相比，MM的一个主要优势是其抗肌无力作用迅速开始(在6周内)，这增加了MM最初治疗将缩短每日皮质类固醇的持续时间/剂量并减少与皮质类固醇相关的毒性负担的可能性。这项研究将提供有关MM治疗MG的安全性和有效性的关键数据，并代表着朝着器官特异性、非皮质类固醇免疫抑制治疗这种疾病的目标迈出的重要一步

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The goal of this study is to test the hypothesis that MM (2.5 Grams /day) in combination with prednisone (20 mg/d) provides better control of myasthenic signs and symptoms than prednisone alone in the initial management of MG. An open label extension will supply further information about the safety and tolerability of MM at does ranging from 2.5 to 3 grams/day and will give preliminary information about tapering and discontinuing prednisone in patients maintained on MM. RESEARCH PLAN: This is a randomized, double-blind, placebo-controlled, multicenter, trial of MM with moderate-dose prednisone in patients whose MG is not severe. Double blind treatment is three (3) months followed by a 6 month open late phase. Expected multicenter enrollment is 80 patients. METHODS: Subjects will be randomized to receive prednisone 20 mg /day with placebo or with MM 2.5 g/d. Blood work and ADL questionnaire will be administered to assure safety and detect initial improvement. Safety evaluation and assessment of disease severity will occur after 4, 8, and 12 weeks on study medication. Open Label will continue for with safety evaluation and assessments at 13, 14, 15, 16, 20, 28 and 36 weeks. CLINICAL RELEVANCE: MG is an uncommon autoimmune disease, affecting about 50,000 patients in the US, in which antibodies to the acetylcholine receptor cause failure of neuromuscular transmission, pathologic fatigue, and weakness. Immunosuppression is used in most MG patients but current treatments are not uniformly effective and carry risk of serious side effects. Preliminary reports have suggested that mycophenolate mofetil (MM), a selective inhibitor of T amp; B-cells used to prevent allograft rejection, is effective and well tolerated in MG. A major advantage of MM, compared to the steroid-sparing agents currently in use, is the rapid onset (within 6 weeks) of its anti-myasthenic action, raising the possibility that initial treatment with MM will lessen the duration/dose of daily corticosteroids and reduce the burden of corticosteroid-related toxicity. This study will furnish key data about the safety and efficacy of MM in MG and represents an important step toward the goal of organ-specific, corticosteroid-free immunosuppressive treatment for this diseas