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）：将进行第一阶段研究，以确定罗伊氏乳杆菌 DSM 17938（每日 10^8 CFU）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先进行一期研究，证明罗伊氏乳杆菌（葵花籽油中）滴剂对成人的安全性和有效性。 该研究包括单剂量 5 x 10^8、每天 5 滴罗伊氏乳杆菌；我们将确定对接受推荐制造剂量的受试者的影响（如果有）。 这项研究将持续一年，其中前两个月最为关键。 在前两个月内，患者将参加 7 次预约，并保持每两周一次的日记、血清化学分析以及 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，并使 FDA 能够批准罗伊氏乳杆菌用于患有肠绞痛（和其他疾病）的婴儿的研究。 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 使命相关，该提案被设计为健康成人的 I 期研究，测试罗伊氏乳杆菌的功效和耐受性。 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TLR2和TLR4的表达；人PBMC中Treg细胞的数量；和粪便钙卫蛋白测定。我们还希望未来能够开展益生菌治疗胃肠道疾病的研究。 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，更具体地说是l。罗伊特里。 证据可以识别胃肠道疾病的早期发作，例如肠易激综合症。 罗伊氏乳杆菌可能有助于预防急性腹泻和过敏性疾病。 我们将演示 l 的治疗情况。罗伊氏菌在健康成人中显示出有效性和耐受性。另外，如果从生理上来说，l。罗伊氏菌对人体系统具有自身免疫作用，更具体地说是 Toll 样受体和细胞因子，可识别特定菌株的促炎性或抗炎性。可以确定特定益生菌及其对胃肠系统影响的机制。