Prednisone Ocular Myasthenia Gravis Trial Planning Grant

描述(申请人提供)：重症肌无力是一种慢性自身免疫性神经肌肉疾病，以肌肉无力为特征，在活动期间加剧，休息后改善，可导致危及生命的并发症，如呼吸衰竭。通常患者的眼肌无力局限于眼肌，但在1到2年内，大约三分之二的患者发展为全身性疾病。这项申请是为支持眼肌无力重症患者临床试验的最终计划而提出的。一项有240名患者参加的双掩蔽、安慰剂对照、随机临床试验将被设计用来检验这样一种假设，即用强的松进行皮质类固醇治疗，剂量不会引起重大不良事件或副作用，将减少全身肌肉受累的发生率，并在一年内改善与疾病相关的视力残疾。降低全身性重症肌无力的风险将降低总体残疾、肌无力危机、住院和昂贵的侵入性治疗(如胸腺切除术和血浆透出术)的风险。此外，如果建议的治疗方法减少复视并恢复双眼功能，患者可能能够更好地执行日常生活活动，如阅读、驾驶汽车、操作机械和工作。如果慢性小剂量糖皮质激素在减少全身性疾病的发生率和减少视力障碍方面是有益的，它将取代许多神经科医生使用的中到大剂量的治疗；通过避免高血压、感染、高血糖和骨质疏松症等重大并发症。在一年的获奖期内，我们的活动将致力于制定程序手册，最终确定研究方案，招募诊所地点，概述数据管理系统，详细说明研究药物的分配和跟踪，创建临床和患者手册，并通过执行委员会会议和电话会议准备和提交研究试验的拨款申请。

DESCRIPTION (provided by applicant): Myasthenia gravis, a chronic autoimmune neuromuscular disease, is characterized by muscle weakness that increases during periods of activity and improves after periods of rest and can result in life-threatening complications such as respiratory failure. Often patients present with weakness confined to the ocular muscles, Ocular Myasthenia Gravis but within 1 to 2 years, approximately two-thirds of patients develop generalized disease. This application is for funding to support the final planning of a clinical trial for patients with Ocular Myasthenia Gravis. A double masked, placebo-controlled, randomized clinical trial of 240 patients will be designed to test the hypothesis that corticosteroid therapy with prednisone, in doses that do not cause major adverse events or side effects, will reduce the incidence of systemic muscle involvement and improve disease-related visual disability at one year. Reducing the risk of Generalized Myasthenia Gravis will decrease the risk of overall disability, Myasthenic crises, hospitalizations, and costly invasive therapies such as thymectomy and plasmaphoresis. In addition, if the proposed therapy reduces double vision and restores binocular function, patients may be better able to perform activities of daily living such as reading, driving an automobile, handling machinery, and work. If chronic low dose corticosteroids are beneficial in decreasing the incidence of generalized disease as well as reducing visual disability, it will replace the moderate to high dose therapy used by many neurologists; there by avoiding the significant complications of hypertension, infections, hyperglycemia, and osteoporosis. Our activities during the one year award period will be directed towards developing a Manual of Procedures, finalizing Study protocol, recruiting clinic sites, outlining data management systems, detailing Study drug distribution and tracking, creating clinic and patient brochures, and preparing and submitting the grant applications for the Study trial, via executive committee meetings and teleconferences.