Mindfulness, Stress, and IBD Flare-Up

描述（由申请人提供）：背景。目前炎症性肠病（IBD）的治疗远非理想，许多IBD患者（Pts）对传统药物不满意，已转向CAM，希望找到更多的疗效和更少的毒性。越来越多的证据表明，压力的经验（压力源）触发突发和/或恶化IBD的过程中，我们的试点数据和文献综述表明，IBD患者有高水平的压力（更频繁和更严重的反应，压力源）。高压力可以激活脑肠轴（BGA），导致肠道肥大细胞释放促炎介质，并在肠道中创造促炎/促氧化环境，这增加了突发的风险。我们推测，基于CAM的减压技术可能会防止这些影响。这是创新的，因为常规疗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，并促进各种健康状况下的正常免疫功能。但是正念减压疗法还没有在IBD中进行过测试，其各种作用的机制在很大程度上是未知的。假设：正念减压疗法将减少应激反应，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。确定减压是否与1年的正念减压疗法有关 中重度溃疡性结肠炎（UC）患者，但处于缓解期 减轻或预防炎症、氧化性组织损伤和突发。方法：我们将在I/IIa期随机、双盲、安慰剂对照试验中招募100名患者。患者将被分配到（a）MBSR训练（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），类似的会议，但只有非IBD重点教育信息，通过结构化讲座。两组均随访1年或直至发作。预测：（1）主要结果MBSR将减少肠道炎症（粪便钙卫蛋白）;（2）次要结果MBSR将减少氧化性组织损伤（粘膜蛋白氧化），减少应激反应（24小时尿皮质醇、ACTH、心理问卷），预防发作（临床、内窥镜和组织学指标），并具有良好的可接受性和耐受性（结构式问卷、拒绝参加率、辍学率）。重要性：验证我们的假设将（1）建立使用MBSR预防IBD发作的概念证据，（2）为未来的临床试验（我们设想的R 01）提供关于效应量，可行性（MBSR的接受和耐受性）和适当的对照组的信息，（3）澄清压力在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.