Mindfulness, Stress, and IBD Flare-Up

描述（由申请人提供）：背景。目前炎症性肠病（IBD）的治疗还远远不够理想，许多对常规药物不满意的IBD患者（Pts）转向CAM，希望找到更有效、更低毒性的治疗方法。越来越多的证据表明，压力经历（压力源）会引发IBD病程的突然发作和/或恶化，我们的试点数据和文献综述表明，IBD患者有高水平的压力（对压力源的反应更频繁和更严重）。高压力会激活脑肠轴（BGA），导致肠肥大细胞释放促炎介质，并在肠道中创造促炎/促氧化环境，从而增加爆发的风险。我们推测，基于cam的应力降低技术可能会防止这些影响。这是创新的，因为传统疗法侧重于减轻粘膜免疫炎症反应，而我们的方法侧重于预防它们。正念减压（MBSR）计划是一种广泛使用的CAM干预措施，可以减少压力反应，减轻炎症，促进各种健康状况下的正常免疫功能。但正念减压疗法尚未在IBD中进行测试，其各种作用的机制在很大程度上是未知的。假设：正念减压会减少应激反应，使肠道环境正常化，并降低IBD患者的发作频率和严重程度。目标。确定中重度溃疡性结肠炎（UC）患者在缓解期进行1年MBSR练习后，压力减轻是否能减轻或预防炎症、氧化组织损伤和急性发作。方法：我们将招募100名患者进行I/IIa期随机、双盲、安慰剂对照试验。患者将被分配到(a)正念减压训练（小组会议，每次1.5小时，8周；n=50;）或(b)时间和注意力对照组（n=50），进行类似的会议，但只通过结构化讲座提供非ibd重点教育信息。两组患者将被随访1年或直到病情发作。预测：(1)主要结果：MBSR会减少肠道炎症（大便钙保护蛋白）；(2)次要结局：MBSR可减少氧化组织损伤（粘膜蛋白氧化），降低应激反应（24 h尿皮质醇、ACTH、心理反应）。问卷调查)，预防突发事件（临床、内镜和组织学指标），并被广泛接受和容忍（结构化问卷调查、拒绝参与率、退出率）。意义：验证我们的假设将(1)建立使用MBSR预防IBD爆发的概念证明，(2)为未来的临床试验（我们设想R01）提供有关效应大小、可行性（MBSR的接受和耐受性）和适当对照组的信息，(3)阐明压力在IBD中的作用和MBSR作用的机制。

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.