Mindfulness, Stress, and IBD Flare-Up

简介(申请人提供)：背景。目前炎症性肠病(IBD)的治疗还很不理想，许多对传统药物不满意的IBD患者(PT)纷纷转向CAM，希望找到更有效、更少毒性的治疗方法。越来越多的证据表明，应激经历(应激源)会触发IBD病程的突发和/或恶化，我们的试点数据和文献回顾表明，IBD Pts具有高水平的压力(对应激源的反应更频繁和更严重)。高应激可激活脑肠轴(BGA)，导致肠道肥大细胞释放促炎介质，并在肠道内创造促炎/促氧化环境，从而增加突发事件的风险。我们推测，基于CAM的应力减轻技术可能会阻止这些影响。这是创新的，因为传统的治疗方法侧重于减弱粘膜免疫炎症反应，而我们的方法侧重于预防它们。基于正念的压力减轻(MBSR)计划是一种广泛使用的CAM干预措施，可以在各种健康状况下减少压力反应、减轻炎症并促进正常的免疫功能。但MBSR尚未在IBD中进行测试，其各种影响的潜在机制在很大程度上尚不清楚。假设：MBSR将减少应激反应，使肠道环境正常化，并降低IBD Pts的发作频率和严重程度。目标。目的：确定缓解中重度溃疡性结肠炎(UC)的PTS患者进行MBSR治疗1年是否能减轻或预防炎症、氧化组织损伤和突发事件。方法：我们将在I/IIa期随机、双盲、安慰剂对照试验中招募100名PTS。PTS将被分配到(A)MBSR培训(小组会议，每次1.5小时，8周；n=50；)或(B)时间和注意力控制组(n=50)，类似会议，但只通过有组织的讲座提供非IBD重点的教育信息。这两组人都将被跟踪一年或直到爆发。预测：(1)主要结果MBSR将减少肠道炎症(粪便钙保护素)；(2)次要结果MBSR将减少氧化组织损伤(粘膜蛋白氧化)，降低应激反应(24小时尿皮质醇、ACTH、心理)。(问卷调查)，防止突发事件(临床、内窥镜和组织学指标)，以及良好接受和容忍(结构化问卷、拒绝参与率、辍学率)。意义：验证我们的假设将(1)为使用MBSR预防IBD的突发事件建立概念证据，(2)为未来的临床试验(我们设想R01)提供关于效应大小、可行性(MBSR的接受度和耐受性)和适当的对照组的信息，(3)阐明应激在IBD中的作用和MBSR效应的机制。

DESCRIPTION (provided by applicant): Background. Current treatment of inflammatory bowel diseases (IBD) is far from ideal and many IBD patients (Pts) dissatisfied with conventional medications have turned to CAM hoping to find more efficacy and less toxicity. Mounting evidence indicates that stressful experiences (stressors) trigger flare-up and/or worsen IBD's course, and our pilot data and review of the literature indicate that IBD Pts have high levels of stress (more frequent and more severe responses to stressors). High stress can activate the brain gut axis (BGA), cause intestinal mast cells to release proinflammatory mediators, and create a proinflammatory / prooxidant milieu in the gut, which increases the risk for flare-up. We surmised that CAM-based stress reduction techniques might prevent these effects. This is innovative as conventional therapies focus on attenuating mucosal immuno- inflammatory responses while our approach focuses on preventing them. The mindfulness based stress reduction (MBSR) program is a widely-used CAM intervention that reduces stress responses attenuates inflammation, and promotes normal immune functioning in a variety of health conditions. But MBSR has not been tested in IBD, and mechanisms underlying its various effects are largely unknown. Hypotheses: MBSR will reduce stress responses, normalize the gut milieu, and decrease flare-up frequency & severity in IBD Pts. Aims. To determine whether stress-reduction associated with 1 y of MBSR practice by Pts with moderately severe ulcerative colitis (UC), but who are in remission attenuates or prevents inflammation, oxidative tissue injury and flare-up. Methods: We will enroll 100 Pts in a Phase I/IIa randomized, double-blind, placebo- controlled trial. Pts will be assigned to (a) MBSR training (group sessions, 1.5 h each, 8 wks; n=50 ;) or (b) a time & attention control group (n=50) with similar sessions but only non-IBD focused educational information through structured lectures. Both groups will be followed for 1 y or until flare up. Predictions: (1) primary outcome MBSR will decrease gut inflammation (stool Calprotectin); (2) secondary outcomes MBSR will decrease oxidative tissue injury (mucosal protein oxidation), decrease stress responses (24 h urinary cortisol, ACTH, psych. questionnaires), prevent flare-up (clinical, endoscopic & histological indices), and be well- accepted and tolerated (structured questionnaires, rate of refusal to participate, drop-out rate). Significance: Validating our hypotheses will (1) establish proof of concept for use of MBSR in preventing flare up in IBD, (2) inform a future clinical trial (we envision an R01) regarding effect size, feasibility (acceptance and tolerance of MBSR) and appropriate control groups, (3) clarify the role of stress in IBD and mechanisms for MBSR effects.