Methotrexate Response In Treatment of UC

描述（由申请人提供）： 尽管接受了5-氨基水杨酸盐和类固醇治疗，但活动性溃疡性结肠炎（UC）患者仍面临临床挑战，因为与活动性克罗恩病（CD）患者相比，药物治疗的替代方案要少得多。甲氨蝶呤（MTX）是CD患者的既定治疗药物。到目前为止，在UC患者中使用MTX的小型临床试验未能证明显着的临床益处。然而，在这些比较研究中，与CD试验相比，UC试验中使用的MTX剂量较低（分别为12.5 mg和25 mg），并且使用了不同的给药途径（UC中口服，CD中肌内）。相比之下，回顾性收集的数据表明，在UC患者中使用与CD患者相同的MTX给药途径和剂量具有显著的治疗疗效。我们假设25 mg MTX皮下应用在UC患者中具有显著的临床疗效，这些患者患有类固醇依赖性疾病过程或已经失败或不耐受抗TNF药物、硫唑嘌呤或6-MP治疗。利用克罗恩病和结肠炎临床研究联盟的框架，我们计划进行一项多中心、安慰剂对照的临床研究，研究MTX在活动性UC患者中的短期和长期疗效。本研究计划在25-30家中心纳入160例患者。本U34申请的具体范围是最终确定研究方案和所有相关研究手册和表格（操作手册、数据和安全性监测计划、研究者手册、知情同意书）。我们还将为本研究制定和建立一个具体的基于网络的数据监测和管理计划。此外，将启动IRB批准流程，并与所有相关研究中心签订分包合同，并与中心药房和中心实验室签订合同和标准操作规程。

DESCRIPTION (provided by applicant): Patients with active ulcerative colitis (UC) despite of a therapy with 5-aminosalicylates and steroids represent a clinical challenge, since the alternatives in medical therapy are considerably fewer compared to those for patients with active Crohn's disease (CD). Methotrexate (MTX) is an established therapeutic agent in patients with CD. Small clinical trials employing MTX in UC patients failed so far to demonstrate a significant clinical benefit. In these comparative studies, however, lower MTX doses were applied in the UC trials compared to CD trials (12.5 vs 25 mg, respectively) and different routes of administration (oral in UC, intramuscularly in CD) were used. In contrast, retrospectively collected data employing the same route of application and dose of MTX in UC patients as in patients with CD suggest a significant therapeutic efficacy. We hypothesize that 25 mg subcutaneously applied MTX has significant clinical efficacy in UC patients, who suffer from steroid-dependent disease course or who have failed or did not tolerate a therapy with anti-TNF agents, azathioprine or 6-MP. Using the framework of the Crohn's and Colitis Clinical Research Alliance we plan to perform a multicenter, placebo-controlled clinical study investigating the short and long-term efficacy of MTX in patients with active UC. The study is planned for 160 patients in 25-30 centers. The specific scope of this U34 application is to finalize the study protocol and all related study manuals and forms (manual of operations, data and safety monitoring plan, investigator brochure, consent forms). We will also develop and establish a specific web-based data monitoring and management plan for this study. Furthermore, the IRB approval process will be initiated and subcontracts will be developed with all involved sites and contracts and standard operating procedures will be established with a central pharmacy and a central laboratory.