A CLINICAL TRIAL OF MYCOPHENOLATE MOFETIL IN MYASTHENIA GRAVIS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。目的：本研究的目的是检验MM（2.5克/天）联合泼尼松（20 mg/天）在MG的初始管理中比单独泼尼松更好地控制肌无力体征和症状的假设。一个开放标签的扩展将提供更多的信息，MM的安全性和耐受性的剂量范围从2.5至3克/天，并将提供初步的信息，逐渐减少和停止泼尼松的患者维持在MM。RESEARCH：这是一个随机的，双盲的，安慰剂对照的，多中心的，试验MM与中等剂量的泼尼松的MG患者是不严重的。双盲治疗为3个月，随后为6个月开放晚期。预期多中心入组80例患者。 方法：受试者将随机接受泼尼松20 mg /d+安慰剂或MM 2.5 g/d。将进行血液检查和ADL问卷调查，以确保安全性并检测初始改善。安全性评价和疾病严重程度评估将在研究药物治疗4、8和12周后进行。开放标签将继续在第13、14、15、16、20、28和36周进行安全性评价和评估。 临床相关性：MG是一种不常见的自身免疫性疾病，在美国影响约50，000名患者，其中乙酰胆碱受体的抗体导致神经肌肉传递失败，病理性疲劳和虚弱。大多数MG患者使用免疫抑制剂，但目前的治疗方法并不一致有效，并有严重副作用的风险。霉酚酸酯（MM）是一种选择性T细胞和B细胞抑制剂，用于预防同种异体移植物排斥反应，对MG有效且耐受性良好。与目前使用的类固醇保留药物相比，MM的主要优势是其抗肌无力作用的快速起效（6周内），这增加了MM初始治疗将减少每日皮质类固醇的持续时间/剂量并降低皮质类固醇相关毒性负担的可能性。这项研究将提供关于MM在MG中的安全性和有效性的关键数据，并代表了朝着器官特异性、无皮质类固醇免疫抑制治疗该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