Phase I: Safety and Tolerance of Lactobactocillus reuteri in Adults

第一阶段：罗伊氏乳杆菌在成人中的安全性和耐受性

• 批准号: 7920228
• 负责人: JON Marc RHOADS
• 金额: $ 11.4万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7920228
• 关键词: Abdominal colic; Acute; Adult; Adverse event; Age; Allergic Disease; Anti-Inflammatory Agents; Anti-inflammatory; Appointments and Schedules; Autoimmune Process; Bacteria; Biological Assay; Carbohydrates; Cell Count; Cells; Chemistry; Child; Clinical Research; Clostridium; Complementary and alternative medicine; Complex; Data; Desire for food; Diagnostic and Statistical Manual; Diarrhea; Dose; Drops; Exploratory/Developmental Grant; Future; Gases; Gastrointestinal Diseases; Goals; Health; Human; Immune system; Infant; Infantile Colic; Inflammatory; Inflammatory disease of the intestine; Intestinal Diseases; Ionomycin; Irritable Bowel Syndrome; Lactobacillus; Leukocyte L1 Antigen Complex; Mission; NIH Program Announcements; National Center for Complementary and Alternative Medicine; Newborn Infant; Patients; Peripheral Blood Mononuclear Cell; Phase; Placebos; Prevention; Probiotics; Production; Regulatory T-Lymphocyte; Research; Research Ethics Committees; Safety; Science; Serum; Sleep; Sunflower Oil; Symptoms; System; TLR2 gene; TLR4 gene; Technology; Therapeutic Intervention; Toll-like receptors; United States National Institutes of Health; Visit; base; cytokine; design; diaries; early onset; efficacy testing; follow-up; gastrointestinal; gastrointestinal system; gut microflora; improved; in vivo; phase 1 study; public health relevance

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.

描述（由申请人提供）：将进行1期研究，以确定L的安全性和耐受性。reuteri DSM 17938，每天10^8 CFU，治疗健康成人。 FDA要求我们进行一项1期研究，以证明L。在进行我们的婴儿绞痛研究之前，在成人中使用reuteri（向日葵籽油）。 该研究包括单剂量5 × 10^8，每天5滴L。reuteri;我们将确定接受推荐生产剂量的受试者中的影响（如有）。 这项研究将在一年内进行，前两个月是最关键的。 在前两个月，患者将参加7次预约，并保持每两周一次的日记，血清化学，以及3个月和6个月的随访。 将记录不良事件。 我们已于2009年4月24日收到该项目的最终IRB批准（#08-0266）。 这项研究的结果预计将显示安全性和耐受性，并将使FDA批准L。婴儿肠绞痛（和其他疾病）的reuteri。 长期目标是阐明儿童（0 - 18岁）肠道疾病的机制，并确定可行的治疗方法。 与NIH的使命相关，该提案被设计为在健康成人中进行的I期研究，以测试L. reuteri。 但此外，我们将确定LR对PMA加离子霉素刺激后外周血单核细胞（PBMC）中细胞因子组的基线和刺激水平的影响;人PBMC中TLR 2和TLR 4的表达;人PBMC中Treg细胞的数量;以及粪便钙卫蛋白测定。我们还希望进行未来的研究益生菌治疗干预胃肠道疾病。 需要更多的信息来描述复杂的肠道菌群-免疫系统与新生儿胃肠道疾病（如绞痛）的关系。 公共卫生相关性： 我们的研究将为益生菌的安全性提供证据，更具体地说，L。reuteri。 证据可以确定胃肠道疾病的早期发作，如肠易激综合征。 L. reuteri可能有助于预防急性腹泻和过敏性疾病。 我们将证明，如果治疗L。在健康成人中的罗伊氏试验显示出有效性和耐受性。如果生理上，L。罗伊氏菌对人类系统具有自身免疫作用，更具体地，Toll样受体和细胞因子将特定菌株鉴定为促炎或抗炎。可以确定特定益生菌的机制及其对胃肠道系统的影响。