当前位置: X-MOL 学术Clin. Gastroenterol. Hepatol. › 论文详情
Effects of Colesevelam on Bowel Symptoms, Biomarkers, and Colonic Mucosal Gene Expression in Patients with Bile Acid Diarrhea in a Randomized Trial.
Clinical Gastroenterology and Hepatology ( IF 7.958 ) Pub Date : 2020-02-20 , DOI: 10.1016/j.cgh.2020.02.027
Priya Vijayvargiya,Michael Camilleri,Paula Carlson,Asha Nair,Sara Linker Nord,Michael Ryks,Deborah Rhoten,Duane Burton,Irene Busciglio,Alan Lueke,W Scott Harmsen,Leslie J Donato

BACKGROUND & AIMS Approximately one-third of patients with IBS-diarrhea (IBS-D) have increased bile acid (BA) synthesis or excretion. An open-label study showed benefits of colesevelam on bowel functions, consistent with luminal BA sequestration by colesevelam. We compared the effects of colesevelam vs placebo on symptoms and gene expression patterns in the sigmoid colon mucosa in patients with BA diarrhea associated with IBS-D. METHODS We performed a double-blind, parallel-group study of 30 adults with IBS-D and evidence of increased BA synthesis or fecal excretion, from December 2017 through December 2018 at a single center. Patients were randomly assigned (1:1) to groups given colesevelam (3 tablets, 625 mg each) or matching placebo, orally twice daily for 4 weeks. Stool diaries documented bowel functions for 8 days before and 28 days during colesevelam or placebo. Stool and fasting serum samples were collected for analyses of fecal BAs and serum levels of C4 and FGF19. We measured colonic transit by scintigraphy, mucosal permeability by in vivo excretion of saccharide probes, and mRNA levels in rectosigmoid biopsies. All measurements were made at baseline and on the last days of treatment. The primary endpoints were change in total fecal BA concentration and stool consistency. RESULTS Compared with placebo, colesevelam was associated with significant changes in sequestered fecal total BA excretion (P<.001) and serum levels of C4 and FGF19 (both P<.001), and with a mean increase in fecal level of deoxycholic acid (10%; P=.07) compared to placebo. Colesevelam decreased colon mucosal expression of NR1H4 and P2RY4 and increased expression of GPBAR1, compared with baseline. Stool frequency and consistency, colonic transit, and permeability did not differ significantly between groups. Colesevelam was well tolerated. CONCLUSIONS In a randomized trial, we found that colesevelam increases delivery of total and secondary BAs to stool, hepatic BA synthesis, and colonic mucosal expression of genes that regulate BA, farnesoid X, and GPBAR1 receptors. Larger studies are needed to determine the effects on clinical responses. ClinicalTrials.gov no: NCT03270085.
更新日期:2020-02-21

 

全部期刊列表>>
宅家赢大奖
向世界展示您的会议墙报和演示文稿
全球疫情及响应:BMC Medicine专题征稿
新版X-MOL期刊搜索和高级搜索功能介绍
化学材料学全球高引用
ACS材料视界
x-mol收录
自然科研论文编辑服务
南方科技大学
南方科技大学
西湖大学
中国科学院长春应化所于聪-4-8
复旦大学
课题组网站
X-MOL
深圳大学二维材料实验室张晗
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug