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Dosing and Pilot Efficacy of 2'-Fucosyllactose in Inflammatory Bowel Disease

2-岩藻糖基乳糖治疗炎症性肠病的剂量和试验效果

基本信息

批准号：
10394798
负责人：
LEE ARMISTEAD DENSON
金额：
$ 46.73万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-12 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10394798
关键词：
Adult Anti-Tumor Necrosis Factor Therapy Antibodies Bifidobacterium Biogenesis Biological Assay Butyrates Carbohydrates Child Childhood Chronic Clinical Clinical Research Clinical Trials Crohn&apos s disease Data Diagnosis Dietary Carbohydrates Disease Disease remission Dose Enzymes Epithelial Epithelial Cells Excision Fucose Future Genes Genetic Polymorphism Glucose Growth Health Homeostasis Human Milk Incidence Individual Infant Inflammation Inflammatory Inflammatory Bowel Diseases Intestines Leukocyte L1 Antigen Complex Life Link Lymphocyte Function Metabolic Metagenomics Mitochondria Mucositis Mucous Membrane Oligosaccharides Outcome Patients Pharmaceutical Preparations Phase Placebo Control Placebos Predisposition Production Proteobacteria Randomized Randomized Controlled Trials Regulatory T-Lymphocyte Relapse Risk Safety Specialist Supplementation Symptoms TNF gene Testing Therapeutic Intervention Ulcerative Colitis United States National Institutes of Health Volatile Fatty Acids Withdrawal adalimumab beneficial microorganism clinical practice clinical remission cytokine dietary supplements disorder risk dysbiosis efficacy testing feeding genetic signature gut inflammation gut microbiota improved outcome indexing infliximab innovation intestinal epithelium metatranscriptomics microbial microbiota mouse model novel prebiotics prevent response young adult

项目摘要

The Inflammatory Bowel Diseases (IBD), Crohn Disease (CD) and Ulcerative Colitis (UC), are chronic and debilitating disorders with peak incidence in the second and third decades of life. While considerable progress has been made in optimizing medications to achieve remission, relapse is common and unpredictable. Altered microbiota likely drive gut inflammation and clinical relapses. Microbiota-accessible dietary carbohydrates with beneficial health effects, known as “prebiotics,” hold promise for restoring healthy gut microbiota in IBD and preventing clinical relapse. Here, we propose the first studies of the prebiotic human milk oligosaccharide, 2’-fucosyllactose (2’-FL), for maintaining remission in IBD. Our overarching hypothesis is that 2’-FL supplementation in IBD will be safe and well tolerated, while increasing fecal Bifidobacterium abundance and butyrate in a dose dependent manner. We will test this hypothesis by conducting a randomized, placebo- controlled dose-ranging study and completing the following Aims: Aim 1. Define dose dependent safety and tolerability of 2’-FL as a dietary supplement in IBD. We will test 1, 5, or 10 gm 2’-FL compared to 2 gm glucose placebo as a daily dietary supplement in pediatric and young adult IBD patients in stable remission receiving infliximab or adalimumab anti-TNF therapy. Safety and tolerability will be assessed using validated clinical disease activity indices, a novel electronic symptom tracker, and fecal calprotectin. Aim 2. Define dose dependent efficacy of 2’-FL as a dietary supplement in IBD. We will utilize our established fecal metagenomic, metatranscriptomic, and metabolite assays to test the effect of a range of 2’FL doses upon the gut microbial community and associated metabolic functions with a focus upon butyrate production. Efficacy will be assessed by determining the dose dependent effect of 2’-FL upon increased fecal Bifidobacterium and butyrate abundance. We will account for FUT2 secretor status in the analysis. These studies will have a high impact in the field by providing critical phase I/IIa safety and efficacy data in support of a phase III RCT using our NIH-supported IBD clinical research network to test the efficacy of 2’-FL in directly modulating beneficial microbiota and thereby enhancing sustained clinical remission. Ultimately the proposed studies will promote a fundamental shift in clinical practice towards personalized microbial therapeutic interventions.

炎症性肠病（IBD），克罗恩病（CD）和溃疡性结肠炎（UC）是慢性和慢性的