Road to discovery for combination probiotic BB-12 with LGG in treating autism spectrum disorder

益生菌 BB-12 与 LGG 组合治疗自闭症谱系障碍的发现之路

• 批准号: 9766942
• 负责人: JON Marc RHOADS
• 金额: $ 41.7万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-20 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766942
• 关键词: 15 year old; Abdomen; Abdominal Pain; Acute; Adolescent; Adult; Affect; Amino Acids; Ammonia; Antiinflammatory Effect; Bacteroides; Behavior; Behavioral; Bifidobacterium; Biological; Biological Markers; Blinded; Blood; Blood Tests; Child; Colony-forming units; Complex; Constipation; Consumption; DNA sequencing; Denmark; Diagnosis; Diarrhea; Dose; Enrollment; FDA approved; Feces; Food; Future; Gastrointestinal Diseases; Glutamates; Health; High Pressure Liquid Chromatography; Incidence; Infant; Inflammation; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Intestinal permeability; Intestines; Irritable Bowel Syndrome; Lactobacillus; Lactobacillus casei rhamnosus; Leukocyte L1 Antigen Complex; Link; Measures; Medicine; Meta-Analysis; Multicenter Trials; Oral; Pain; Parents; Participant; Pattern; Permeability; Phase; Phenols; Placebos; Plasma; Population; Probiotics; Quality of life; Questionnaires; Randomized; Recurrence; Reporting; Research Personnel; Research Project Grants; Ribosomal DNA; S100A9 gene; Safety; Severities; Signal Transduction; Site; Stomach Diseases; Symptoms; Testing; United States Food and Drug Administration; Upper Respiratory Infections; Visit; Volatile Fatty Acids; Vomiting; aged; arm; autism spectrum disorder; autistic; autistic behaviour; autistic children; bacterial community; base; cell motility; computer program; effective therapy; fecal microbiota; gastrointestinal; gastrointestinal function; gastrointestinal symptom; improved; inattention; indexing; instrument; interest; maltodextrin; metabolic profile; microbial; microbial community; microbiota; microbiota metabolites; public health relevance; randomized placebo controlled trial; reduce symptoms; safety and feasibility; side effect; social; sugar; systematic review; treatment duration; trend; trial design; university student; zonulin; 15 year old; Abdomen; Abdominal Pain; Acute; Adolescent; Adult; Affect; Amino Acids; Ammonia; Antiinflammatory Effect; Bacteroides; Behavior; Behavioral; Bifidobacterium; Biological; Biological Markers; Blinded; Blood; Blood Tests; Child; Colony-forming units; Complex; Constipation; Consumption; DNA sequencing; Denmark; Diagnosis; Diarrhea; Dose; Enrollment; FDA approved; Feces; Food; Future; Gastrointestinal Diseases; Glutamates; Health; High Pressure Liquid Chromatography; Incidence; Infant; Inflammation; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Intestinal permeability; Intestines; Irritable Bowel Syndrome; Lactobacillus; Lactobacillus casei rhamnosus; Leukocyte L1 Antigen Complex; Link; Measures; Medicine; Meta-Analysis; Multicenter Trials; Oral; Pain; Parents; Participant; Pattern; Permeability; Phase; Phenols; Placebos; Plasma; Population; Probiotics; Quality of life; Questionnaires; Randomized; Recurrence; Reporting; Research Personnel; Research Project Grants; Ribosomal DNA; S100A9 gene; Safety; Severities; Signal Transduction; Site; Stomach Diseases; Symptoms; Testing; United States Food and Drug Administration; Upper Respiratory Infections; Visit; Volatile Fatty Acids; Vomiting; aged; arm; autism spectrum disorder; autistic; autistic behaviour; autistic children; bacterial community; base; cell motility; computer program; effective therapy; fecal microbiota; gastrointestinal; gastrointestinal function; gastrointestinal symptom; improved; inattention; indexing; instrument; interest; maltodextrin; metabolic profile; microbial; microbial community; microbiota; microbiota metabolites; public health relevance; randomized placebo controlled trial; reduce symptoms; safety and feasibility; side effect; social; sugar; systematic review; treatment duration; trend; trial design; university student; zonulin

Project Abstract Road to discovery for Combination Probiotic Strain: BB-12 with LGG in treating autism spectrum disorders Stomach problems are common in children with autism. The proposed research project will study children with autism spectrum disorders (ASD), 4-15 years of age, who are complaining of recurring gastrointestinal (GI) symptoms, such as abdominal pain, constipation, and vomiting. These gastrointestinal problems are often associated with abnormal behavior, such as irritability. Our group is planning to test if at two different doses of a probiotic (defined as a bacterial product which when consumed in adequate quantity improves health) can benefit these children with GI symptoms. Oral doses of the probiotic we have selected (Lactobacillus rhamnosus GG and Bifidobacterium lactis BB-12, BB-12+LGG) to be tested are: a straw with 2 billion colony forming units (CFUs), a straw with 10 billion CFUs, and a placebo straw. We plan to enroll 70 eligible subjects with confirmed ASD and randomize them to placebo, low dose, and high dose of BB-12+LGG once daily at 1:2:2 ratio. The probiotic, to be added to food, may improve abdominal complaints which we hypothesize may produce changes in autistic behaviors that accompany these GI symptoms. Even though probiotics are widely available, the U.S. Food and Drug Administration requires that we demonstrate that this particular combination probiotic is safe in children before we can undertake a large multi-center trial to see if BB-12+LGG is effective at different doses in children with ASD. Based on previous trials in adults and adolescents, we expect no serious side effects from the use of BB-12+LGG. There will be 4 visits over 90 days. We expect to see a trend toward improvement of autistic behavior and GI symptoms by the end of the 56 days of treatment with BB-12+LGG at the highest dose. The pain and abnormal behaviors will be recorded using validated questionnaires. This study incorporates an Integrated Omics approach. Several blood and stool tests will be tested as potentially useful biomarkers of intestinal health in ASD, including a test of gut permeability (zonulin), a blood test for systemic inflammation (S100A9), and a stool test for inflammation (calprotectin). We will concomitantly measure bacterial communities in the stool (using 16S ribosomal DNA sequencing) and we will measure key metabolites in the blood and stool that have been proposed to contribute to GI symptoms in children with ASD (using high performance liquid chromatography). If an optimal dose of BB-12 + LGG is found to be safe and shows a signal toward improvement with respect to GI or autistic symptoms, we plan to study this probiotic in a larger, multi-center trial, using adaptive trial design.

项目摘要 结合益生菌菌株的发现之路：与LGG进行治疗的BB-12 自闭症谱系障碍 自闭症儿童胃病很常见。拟议的研究项目将 研究儿童自闭症谱系障碍（ASD），4-15岁，他们抱怨 胃肠道（GI）症状，例如腹痛，便秘和呕吐。 这些胃肠道问题通常与异常行为有关，例如 易怒。我们的小组计划在两种不同剂量的益生菌中测试（定义为 细菌产品在足够数量的食用时会改善健康）可以受益 这些患有胃肠道症状的孩子。我们选择的益生菌的口服剂量（乳酸杆菌 要测试的Rhamnosus GG和双歧杆菌BB-12，BB-12+LGG）是：2 数十亿个殖民地成立单元（CFU），一根稻草，有100亿张CFU和安慰剂稻草。我们计划 招募70名合格受试者，并将其随机授予安慰剂，低剂量和 每天以1：2：2的比例，每天的BB-12+LGG高剂量。可以添加到食物中的益生菌可能 改善我们假设的腹部抱怨可能会导致自闭症行为的变化 伴随着这些胃肠道症状。 即使益生菌广泛可用，美国食品和药物管理局也需要 我们证明，这种特殊的组合益生菌在儿童中是安全的 进行大型多中心试验，以查看BB-12+LGG是否在不同剂量的情况下有效 有ASD的孩子。根据成人和青少年以前的试验，我们预计不会认真 使用BB-12+LGG的影响。在90天内将有4次访问。我们希望看到趋势 在56天结束之前改善自闭症行为和胃肠道症状 用最高剂量的BB-12+LGG治疗。疼痛和异常行为将是 使用经过验证的问卷记录。 这项研究结合了一种综合的OMIC方法。几个血液和粪便检查将是 被测试是ASD中肠道健康的潜在有用的生物标志物，包括肠测试 渗透率（Zonulin），全身炎症的血液测试（S100A9）和粪便测试 炎症（钙染色素）。我们将同时测量凳子中的细菌群落 （使用16S核糖体DNA测序），我们将测量血液中的关键代谢产物 提议为ASD儿童的胃肠道症状做出贡献的粪便（使用高 性能液相色谱）。如果发现最佳剂量的BB-12 + LGG是安全的，并且 在胃肠道或自闭症症状方面显示了改善的信号，我们计划研究 这种益生菌在更大的多中心试验中，使用自适应试验设计。