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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.

ABSTRACT: 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.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.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 7?-hydroxy-4-cholesten-3-one (C4) measured.Median serum FGF19 on conventional sequestrant treatment was 28% lower than baseline values in BAD (p?

SUBMITTER: Appleby RN

PROVIDER: S-EPMC5415210 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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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.

Appleby R N RN Bajor A A Gillberg P-G PG Graffner H H Simrén M M Ung K A KA Walters Jrf J

United European gastroenterology journal 20160726 3

<h4>Background</h4>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.<h4>Aim</h4>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.<h ...[more]

PMID: 28507750

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Project description:BackgroundBile acid diarrhoea (BAD) can be severely debilitating and negatively affect patients' quality of life (QoL). We carried out a multi-centre prospective study exploring QoL outcomes in patients with BAD after treatment with colesevelam.MethodsPatients with or without a positive 23-seleno-25-homotaurocholic acid (SeHCAT) scan were recruited and categorised into four groups: SeHCAT negative control group (CG), idiopathic BAD, post-cholecystectomy (PC) and post-terminal ileal resection for Crohn's disease (CD). Patients with a positive SeHCAT were treated with colesevelam and dosing was titrated to symptomatic response. Patients were reviewed at 4- and 8-weekly intervals and QoL was evaluated by EQ-5D-3L, SF-36, IBDQ-32 at each visit (where relevant). Patients with a negative SeHCAT (CG cohort) completed one set of questionnaires before being discharged from the study.Results47 patients (BAD = 24, PC = 12, CD = 11) completed paired QoL questionnaires before and after treatment and 30 CG patients completed a baseline questionnaire. There was a significant improvement in IBDQ-32 mean scores before and after treatment in CD patients [134.6 (95%CI 112.5-156.6) and 158.4 (136.1-180.6), respectively (p = 0.007). Following treatment, BAD patients had significantly improved mean SF-36 scores in the "Role limitation due to physical health" dimension (p = 0.02) and in the overall mental component summary (p = 0.03). Prior to starting treatment, BAD patients had the lowest scores in the 'activity' dimension of the EQ-5D-3L (p = 0.04), which improved significantly after treatment (p = 0.002). Overall, the BAD and CD cohort showed improved mean scores with treatment in all components of the SF-36 and EQ-5D-3L, while the PC cohort showed a general decline in mean scores after treatment. 55% of patients clinically responded to treatment of which 41.7%, 58.3% and 81.8% responded from the BAD, PC and CD groups respectively. Correlations between those deemed as responders with improvements on the SF-36 and EQ-5D dimensions were not statistically significant.ConclusionOur results demonstrate improved QoL in the BAD and CD cohort with treatment. Further larger studies are recommended specifically investigating the PC cohort and whether patients may improve with newer treatments such as FXR agonists. Trial registration Ethical approval REC Ref: 16/LO/1325.

Dataset Information

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.

Publications

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.

Similar Datasets

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