Effects of conventional and a novel colonic-release bile acid sequestrant, A3384, on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and patients with bile acid diarrhoea

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Title: Effects of conventional and a novel colonic-release bile acid sequestrant, A3384, on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and patients with bile acid diarrhoea
Authors: Appleby, RN
Bajor, A
Gillberg, P-G
Graffner, H
Simren, M
Ung, KA
Walters, JRF
Item Type: Journal Article
Abstract: Background: Primary bile acid diarrhoea (BAD) is associated with increased bile acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid sequestrants are used as therapy, but are poorly tolerated and may exacerbate FGF19 deficiency. Aim: The purpose of this study was to evaluate the pharmacological effects of conventional sequestrants and a colonic-release formulation preparation of colestyramine (A3384) on bile acid metabolism and bowel function in patients with BAD. Methods: Patients with seven-day 75selenium-homocholic acid taurine (SeHCAT) scan retention <10% were randomised in a double-blind protocol to two weeks treatment with twice-daily A3384 250 mg (n = 6), 1 g (n = 7) or placebo (n = 6). Thirteen patients were taking conventional sequestrants at the start of the study. Symptoms were recorded and serum FGF19 and 7α-hydroxy-4-cholesten-3-one (C4) measured. Results: Median serum FGF19 on conventional sequestrant treatment was 28% lower than baseline values in BAD (p < 0.05). C4 on conventional sequestrant treatment was 58% higher in BAD (p < 0.001). No changes were seen on starting or withdrawing A3384. A3384 improved diarrhoeal symptoms, with a median reduction of 2.2 points on a 0–10 Likert scale compared to placebo, p < 0.05. Conclusions: Serum FGF19 was suppressed and bile acid production up-regulated on conventional bile acid sequestrants, but not with A3384. This colonic-release formulation of colestyramine produced symptomatic benefit in patients with BAD.
Issue Date: 26-Jul-2016
Date of Acceptance: 1-Jul-2016
URI: http://hdl.handle.net/10044/1/48081
DOI: https://dx.doi.org/10.1177/2050640616662432
ISSN: 2050-6406
Publisher: SAGE PUBLICATIONS INC
Start Page: 380
End Page: 388
Journal / Book Title: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL
Volume: 5
Issue: 3
Copyright Statement: © 2016 The Author(s). Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2050640616662432
Sponsor/Funder: Imperial College Healthcare NHS Trust
Funder's Grant Number: FR650
Keywords: Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
Bile acid sequestrants
colestyramine
fibroblast growth factor 19
bile acid malabsorption
bile acid diarrhoea
chronic diarrhoea
irritable bowel syndrome
IRRITABLE-BOWEL-SYNDROME
DIURNAL-VARIATION
MALABSORPTION
CHOLESTYRAMINE
COLESEVELAM
PREVALENCE
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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