Test-Treat strategy to prevent ulcerative colitis relapse

描述（由申请人提供）： 博士James刘易斯是宾夕法尼亚大学医学和流行病学副教授，在那里他一直积极参与与炎症性肠病和药物安全性相关的以患者为导向的研究。他工作的主要主题是评估用于治疗炎症性肠病的药物的安全性，并改善这些患者的治疗策略。 在这项申请中提出的新科学包括一项针对临床静止期溃疡性结肠炎患者的随机对照试验。拟议的研究将测试增加美沙拉嗪剂量是否可以降低粪便钙卫蛋白（FCP）水平，这是一种肠道炎症的标志物，高度预测静止期溃疡性结肠炎患者的复发风险。60名患有静止期溃疡性结肠炎和FCP水平升高的患者将被随机分配至每天增加2 gm的美沙拉嗪剂量或维持当前剂量。6周后将再次测量FCP（主要终点）。第6周时FCP水平降低至50 mcg/gm粪便以下将是主要结局。将使用Fisher精确检验比较两组间达到该结局的患者比例。6周后，所有患者将接受美沙拉嗪治疗，剂量比随机化前即刻处方的剂量高2 gm（即对照组将交叉进入实验组）。将在第12周再次测量FCP。将对所有随机化患者以及因基线时FCP浓度低而从随机化试验中排除的患者进行随访至第48周，以确定临床复发率。 在资助K24期间，刘易斯博士将继续担任胃肠病学研究员、初级教师、居民和对以病人为导向的研究感兴趣的医学生的主要导师。此外，在获奖期间，刘易斯博士将担任该大学临床流行病学科学硕士项目的临床试验轨道主任，从而使他能够进一步扩大他的指导作用。这个K24奖将是必不可少的，让刘易斯博士有足够的时间从临床活动的保护，以继续发展他的研究计划和纪念活动。

DESCRIPTION (provided by applicant): Dr. James Lewis is Associate Professor of Medicine and Epidemiology at the University of Pennsylvania, where he has been actively involved in patient-oriented research related to inflammatory bowel diseases and medication safety. The major theme of his work has been to assess the safety of medications used in the treatment of inflammatory bowel diseases and to improve the therapeutic strategies for these patients. The new science proposed in this application includes a randomized controlled trial for patients with clinically quiescent ulcerative colitis. The proposed study will test whether increasing mesalamine dose can reduce fecal calprotectin (FCP) levels, a marker of intestinal inflammation that is highly predictive of the risk of relapse among patients with quiescent ulcerative colitis. Sixty patients with quiescent ulcerative colitis and elevated FCP levels will be randomized to either increase their mesalamine dose by 2gm per day or to maintain their current dose. FCP will be measured again after 6 weeks (the primary endpoint). Reduction in FCP levels below 50mcg/gm stool at 6 weeks will be the primary outcome. The proportion of patients achieving this outcome will be compared between groups using Fisher's exact test. After 6 weeks, all patients will be treated with mesalamine at a dose 2gm higher than that prescribed immediately prior to randomization (i.e. the control arm will cross-over into the experimental arm). FCP will be measured again at week 12. All randomized patients as well as those who were excluded from the randomized trial because of a low FCP concentration at baseline will be followed to week 48 to determine the rate of clinical relapse. During the period of funding for the K24, Dr. Lewis will continue to serve as primary mentor for gastroenterology fellows, junior faculty, residents and medical students interested in patient oriented research. In addition, during the period of the award, Dr. Lewis will serve as the director of the Clinical Trials track within the University's Master of Science in Clinical Epidemiology Program, thereby allowing him to further expand his mentoring role. This K24 award will be essential to allow Dr. Lewis sufficient protected time from clinical activities to continue to develop his research program and mementoring activities.