Phase I: Safety and Tolerance of Lactobactocillus reuteri in Adults

描述（由申请人提供）：将进行一项一期研究，以确定罗伊氏乳杆菌DSM 17938,10 ^8 CFU每日治疗健康成人的安全性和耐受性。FDA要求我们在进行婴儿绞痛研究之前进行成人罗伊氏乳杆菌滴剂（葵花籽油）的安全性和有效性的1期研究。该研究包括每日单剂量5 × 10^ 8,5滴罗伊氏乳杆菌；如果有影响，我们会确定，受试者是否接受了推荐的制造剂量。这项研究将进行为期一年，前两个月是最关键的。在前两个月，患者将参加7次预约，并保持双周日记、血清化学和3个月和6个月的随访。不良事件将被记录。我们已于2009年4月24日收到IRB对该项目的最终批准（#08-0266）。这项研究的结果预计将显示出安全性和耐受性，并将使FDA批准在患有绞痛（和其他疾病）的婴儿中进行罗伊氏乳杆菌的研究。

DESCRIPTION (provided by applicant): A Phase 1 Study will be conducted in order to determine safety and tolerability of L. reuteri DSM 17938, 10^8 CFU daily, in treating healthy adults. It is required by the FDA that we conduct a Phase 1 study showing the safety and efficacy of L. reuteri (in sunflower oil) drops in adults before conducting our infant colic study. The study includes a single dose 5 x 10^8, 5 drops daily of L. reuteri; and we will determine the effects, if any, in subjects receiving recommended manufactured dose. This study will be conducted over a one year period with the first two months being the most critical. During the first two months, patients will attend 7 scheduled appointments and maintain bi-weekly diaries, serum chemistries, and 3 and 6-month follow-up visits. Adverse events will be recorded. We have received final IRB approval of this project on 4/24/2009 (#08-0266). Results of this study are expected to show safety and tolerability and will enable the FDA to approve studies of L. reuteri in infants with colic (and other illnesses). The long term goals are to elucidate mechanisms of intestinal disease in children ages (0 - 18 years) and identify viable treatments. Relevant to the NIH mission, this proposal is designed as a Phase I Study in Healthy Adults testing the efficacy and tolerability of L. reuteri. But in addition, we will determine effects of LR on baseline and stimulated levels of a cytokine panel in peripheral blood mononuclear cells (PBMC) after stimulation by PMA plus ionomycin; TLR2 and TLR4 expression in human PBMC; number of Treg cells in human PBMC; and fecal calprotectin assay. We also hope to conduct future research on probiotic therapeutic interventions in gastrointestinal diseases. Much more information is needed to characterize the complex gut microflora-immune system in association with gastrointestinal conditions in newborns such as colic. Public Health Relevance: Our studies would provide evidence for safety of probiotics, more specifically l. reuteri. Evidence could identify the early onset of gastrointestinal conditions, such as Irritable Bowel Syndrome. L. reuteri could possibly assist in the prevention of acute diarrhea and allergic disease. We will demonstrate if treatment of l. reuteri in healthy adults shows efficacy and tolerability. Also if physiologically, l. reuteri has an autoimmune effect on the human system, more specifically toll like receptors and cytokines identifying the specific strain as pro-inflammatory or anti-inflammatory. A mechanism could be identified for a particular probiotic and its effects on the gastrointestinal system.