Test-Treat strategy to prevent ulcerative colitis relapse

描述（由申请人提供）： James Lewis 博士是宾夕法尼亚大学医学和流行病学副教授，他一直积极参与与炎症性肠病和药物安全相关的以患者为导向的研究。他工作的主题是评估用于治疗炎症性肠病的药物的安全性并改进这些患者的治疗策略。 本申请中提出的新科学包括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，这是肠道炎症的标志物，可以高度预测静止期溃疡性结肠炎患者复发的风险。 60 名患有静态溃疡性结肠炎且 FCP 水平升高的患者将被随机分配，要么每天增加 2 克美沙拉嗪剂量，要么维持当前剂量。 FCP 将在 6 周后再次测量（主要终点）。 6 周时粪便中 FCP 水平降低至 50mcg/gm 以下将是主要结果。将使用费舍尔精确检验对组间实现这一结果的患者比例进行比较。 6周后，所有患者将接受美沙拉嗪治疗，剂量比随机分组前规定的剂量高2克（即对照组将​​交叉到实验组）。 FCP 将在第 12 周再次测量。所有随机患者以及因基线 FCP 浓度低而被排除在随机试验之外的患者将随访至第 48 周，以确定临床复发率。 在 K24 资助期间，刘易斯博士将继续担任对以患者为导向的研究感兴趣的胃肠病学研究员、初级教师、住院医生和医学生的主要导师。此外，在获奖期间，刘易斯博士将担任该大学临床流行病学理学硕士项目中临床试验轨道的主任，从而使他能够进一步扩大他的指导作用。该 K24 奖项对于让 Lewis 博士有足够的保护时间从临床活动中继续发展他的研究计划和纪念活动至关重要。

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.