Randomized Placebo-Controlled Trial of Glutamine for Patients with IBS

G.Nicholas Verne，医学博士，对授权#AT005291的修订 项目总结 肠易激综合征(IBS)是一种常见的胃肠道疾病，估计有20%的人会受到影响 美国人口。IBS患者的生活质量显著下降，并利用大量的健康 护理资源。IBS患者患有慢性腹痛，伴有腹泻、便秘和/或 腹胀(Verne&Cerda，1997)。已经提出了几种可能导致肠易激综合征的机制，包括： 受体和神经肽的改变，细菌过度生长和微生物区系改变，肠道改变 运输、焦虑和抑郁症状，以及肠膜通透性增加。最近的几个 研究表明，腹泻型肠易激综合征(D-IBS)患者的肠道通透性增加 可能导致慢性胃肠道症状(Dunlop等人，2006年；Spiller 2000；2007；周等人，2009年b)。我们的 实验室最近评估了以腹泻为主的IBS患者，并报告说他们增加了 膜通透性(周等人，2009年)。我们现在已经获得了口服谷氨酰胺的初步证据 补充剂恢复膜通透性并改善这些IBS的慢性胃肠道症状 病人。 基于这些新的发现，我们假设口服谷氨酰胺补充剂将改善IBS 腹泻型IBS患者的症状严重程度分级和肠膜通透性恢复。 我们建议进行一项随机、双盲、安慰剂对照的临床试验，研究谷氨酰胺10克口服 在100名以腹泻为主的IBS患者中，TID与安慰剂10g，po，tid进行8周的比较。肠易激综合征症状 在基线、2周、4周、6周和8周时测量严重程度评分和肠膜通透性。

G. Nicholas Verne, M.D. Revision to Grant # AT005291 PROJECT SUMMARY Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is estimated to affect 20% of the US population. IBS patients have significantly decreased quality of life and utilize large amounts of health care resources. IBS patients suffer from chronic abdominal pain associated with diarrhea, constipation, and/or bloating (Verne & Cerda, 1997). Several mechanisms that may lead to IBS have been proposed including: alterations in receptors and neuropeptides, bacterial overgrowth and altered microbiota, altered intestinal transit, anxiety and depressive symptoms, and increased intestinal membrane permeability. Several recent studies have shown that diarrhea-predominant IBS (D-IBS) patients have increased intestinal permeability that may lead to chronic gastrointestinal symptoms (Dunlop et al., 2006; Spiller 2000; 2007; Zhou et al., 2009b). Our laboratory recently evaluated diarrhea-predominant IBS patients and reported that they have increased membrane permeability (Zhou et al, 2009). We now have obtained preliminary evidence that oral glutamine supplementation restores membrane permeability and improves chronic gastrointestinal symptoms in these IBS patients. Based on these new findings, we hypothesize that oral glutamine supplementation will improve the IBS Symptom Severity Scale and restore intestinal membrane permeability in diarrhea-predominant IBS patients. We propose to conduct a randomized, double-blind, placebo-controlled clinical trial studying glutamine 10 g po tid compared to placebo 10 g po tid for 8 weeks in 100 diarrhea-predominant IBS patients. The IBS Symptom Severity Scale and intestinal membrane permeability will be measured at baseline, 2, 4, 6, and at 8 weeks.