Dataset Information

Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function.

ABSTRACT:

Background & aims

Di-alpha hydroxy bile salt, sodium chenodeoxycholate (CDC), and bile acid binding have unclear effects on colonic transit in health and disease.

Methods

We performed 2 randomized, double-blind, placebo-controlled studies. In healthy volunteers (20 per group), we evaluated the effects of oral placebo, 500 mg, or 1000 mg of CDC (delayed-release, each given for 4 days) on gastrointestinal and colonic transit. A second trial compared the effects of colesevelam (1.875 g, twice daily) versus placebo in 24 patients (12 per group) with diarrhea-predominant irritable bowel syndrome (IBS-D) on transit, daily bowel frequency and consistency, and colonic mucosal permeability. Serum fasting 7alpha-hydroxy-4-cholesten-3-one (7alphaC4) was measured to screen for bile acid malabsorption. Effects of treatments on transit were compared using analysis of covariance with body mass index and 7alphaC4 as covariates.

Results

In healthy volunteers, CDC significantly accelerated colonic transit (at 24 and 48 hours, P = .01 and P < .0001, respectively), increased stool frequency and ease of passage (both P < .001), and evacuation (P = .02), and decreased stool consistency (P < .001). Four of the 24 IBS-D patients had increased serum 7alphaC4 levels. In IBS-D, colesevelam modestly affected overall colonic transit (24 h; P = .22). Emptying of the ascending colon took an average of 4 hours longer in patients given colesevelam compared with placebo; treatment effect was associated with baseline serum 7alphaC4 levels (P = .0025). Colesevelam was associated with greater ease of stool passage (P = .048) and somewhat firmer stool consistency (P = .12). No effects on mucosal permeability or safety were identified.

Conclusions

Sodium chenodeoxycholate in health and colesevelam in IBS-D patients have opposite effects on colonic transit and fecal parameters.

SUBMITTER: Odunsi-Shiyanbade ST

PROVIDER: S-EPMC2822105 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Publications

Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function.

Odunsi-Shiyanbade Suwebatu T ST Camilleri Michael M McKinzie Sanna S Burton Duane D Carlson Paula P Busciglio Irene A IA Lamsam Jesse J Singh Ravinder R Zinsmeister Alan R AR

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20091030 2

<h4>Background & aims</h4>Di-alpha hydroxy bile salt, sodium chenodeoxycholate (CDC), and bile acid binding have unclear effects on colonic transit in health and disease.<h4>Methods</h4>We performed 2 randomized, double-blind, placebo-controlled studies. In healthy volunteers (20 per group), we evaluated the effects of oral placebo, 500 mg, or 1000 mg of CDC (delayed-release, each given for 4 days) on gastrointestinal and colonic transit. A second trial compared the effects of colesevelam (1.875 ...[more]

PMID: 19879973

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Project description:Background & aimsApproximately 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.MethodsWe 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.ResultsCompared 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.ConclusionsIn 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.

Dataset Information

Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function.

Background & aims

Methods

Results

Conclusions

Publications

Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function.

Similar Datasets

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