A Double Blind, Randomized Placebo Controlled Crossover Multiple Dose Study of LJN452 to Assess Safety, Tolerability and Efficacy in Patients With Primary Bile Acid Diarrhea (pBAD).

The purpose of this study is to determine whether LJN452 improves the symptoms of bile acid diarrhea and to assess its safety and tolerability profile in patients with primary bile acid diarrhea (pBAD) to guide decision-making regarding further clinical development in this indication.

Start Date16 Jan 2016

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

NCT01585025 / CompletedPhase 2IIT

Obeticholic Acid Treatment in Patients With Bile Acid Diarrhoea: an Open-label, Pilot Study of Mechanisms, Safety and Symptom Response.

The investigators propose to develop studies of obeticholic acid (OCA) in patients with bile acid diarrhoea. OCA is a semisynthetic bile acid, also known as 6αethylchenodeoxycholic acid or INT747,and is a potent farnesoid X receptor (FXR) agonist. Preliminary data suggests that patients with bile acid diarrhoea have impaired production of the ileal hormone Fibroblast Growth Factor 19 (FGF19). FGF19 is stimulated by FXR agonists, and regulates bile acid synthesis. This study is a pilot, proof-of-concept, open-label study to investigate whether OCA can stimulate FGF19 in bile acid diarrhoea patients to provide a safe and effective treatment.

Start Date01 Apr 2012

Sponsor / Collaborator

Imperial College Healthcare NHS Trust

100 Clinical Results associated with Bile Acid Malabsorption, Primary

100 Translational Medicine associated with Bile Acid Malabsorption, Primary

0 Patents (Medical) associated with Bile Acid Malabsorption, Primary

Literatures (Medical) associated with Bile Acid Malabsorption, Primary

01 Oct 2022·The Lancet Gastroenterology & Hepatology

Safety and efficacy of liraglutide versus colesevelam for the treatment of bile acid diarrhoea: a randomised, double-blind, active-comparator, non-inferiority clinical trial

Article

Author: Vilsbøll, Tina ; Haaber, Anne ; Sonne, David P ; Langholz, Ebbe ; Forman, Julie L ; Brønden, Andreas ; Dragsted, Lars O ; Knudsen, Elisabeth ; Hansen, Svend H ; Knop, Filip K ; Krakauer, Martin ; Kårhus, Martin L

BACKGROUNDBile acid diarrhoea is an underdiagnosed disease estimated to affect 1-2% of the general population. Case reports indicate that the glucagon-like peptide 1 receptor agonist liraglutide might be an effective treatment for bile acid diarrhoea. We aimed to investigate the safety and efficacy of liraglutide for the treatment of bile acid diarrhoea.METHODSWe conducted a randomised, double-blind, active-comparator, double-dummy, non-inferiority clinical trial at the Center for Clinical Metabolic Research at Copenhagen University Hospital-Herlev and Gentofte, Hellerup, Denmark. Patients aged 18-75 years with ⁷⁵selenium-homotaurocholic acid test (SeHCAT)-verified moderate-to-severe primary bile acid diarrhoea were randomly assigned (1:1) to receive liraglutide (one daily subcutaneous injection uptitrated from 0·6-1·8 mg per day over 3 weeks) or colesevelam (three capsules of 625 mg twice daily), the standard of care, for 6 weeks following one run-in week with no treatment. The primary endpoint was the proportion of participants experiencing a reduction in daily stool frequency of 25% or greater after 6 weeks. Data from all participants were included in the analysis of the primary outcome. The non-inferiority limit was set to 15% in favour of colesevelam. This trial is registered with EudraCT (2018-003575-34) and is completed.FINDINGSBetween April 1, 2019, and Jan 31, 2021, 52 patients were enrolled; 26 were assigned to liraglutide and 26 to colesevelam. 20 (77%) of 26 participants on liraglutide and 13 (50%) of 26 on colesevelam experienced a 25% or greater reduction in stool frequency, corresponding to a significant risk difference of -27% in favour of liraglutide (one-sided 95% CI -100 to -6). Liraglutide was therefore superior to colesevelam in reducing daily stool frequency. Mild nausea with a duration of 10-21 days was reported by six participants in the liraglutide group and by one participant in the colesevelam group. No other adverse events were reported.INTERPRETATIONThe superiority of liraglutide compared with colesevelam in reducing stool frequency suggests consideration of liraglutide as a potential new treatment modality for bile acid diarrhoea, although larger confirmatory trials powered for superiority are warranted.FUNDINGNovo Nordisk, Novo Nordisk Foundation, Foundation for the Advancement of Medical Science under The A.P. Møller and Chastine Mc-Kinney Møller Foundation.

01 Aug 2022·GastroenterologyQ1 · MEDICINE

Common Genetic Variants in the Bile Acid Synthesis Enzyme CYP7A1 Are Associated With Severe Primary Bile Acid Diarrhea

Q1 · MEDICINE

Article

Author: Pattni, Sanjeev S ; Nolan, Jonathan D ; Balesaria, Sara ; Johnston, Ian M ; Appleby, Richard N ; Walters, Julian R F

Bile acid diarrhea (BAD) is increasingly recognized as a common cause of chronic bowel disorders including increased stool frequency, urgency, and incontinence, overlapping with irritable bowel syndrome with diarrhea and functional diarrhea.Limitations of these findings are that they are based on a small number of BAD patients and are significant only in severe disease.To understand the relative roles of causative factors in any individual, these genetic factors will need further study, looking at their interactions with environmental agents controlling FGF19 and BA metabolism, including diet and the microbiome.This may then influence subsequent treatments.

01 Feb 2021·The Lancet Gastroenterology & HepatologyQ1 · MEDICINE

The overlap between irritable bowel syndrome and organic gastrointestinal diseases

Q1 · MEDICINE

Review

Author: Aziz, Imran ; Simrén, Magnus

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterised by symptoms of recurrent abdominal pain associated with a change in bowel habit. This condition is one of the most frequent reasons to seek a gastroenterology consultation in primary and secondary care. The diagnosis of IBS is made by identifying characteristic symptoms, as defined by the Rome criteria, and excluding organic gastrointestinal diseases that might otherwise explain these symptoms. Organic conditions that can be mistaken for IBS include coeliac disease, inflammatory bowel disease (IBD), colorectal cancer, and, in those with diarrhoea-predominant symptoms, chronic gastrointestinal infections, microscopic colitis, and primary bile acid diarrhoea. The concept of small intestinal bacterial overgrowth being associated with IBS is shrouded with controversy and uncertainty, mainly because of invalid tests due to poor sensitivity and specificity, potentially leading to incorrect assumptions. There is insufficient evidence to link IBS-type symptoms with exocrine pancreatic insufficiency or with symptomatic uncomplicated diverticular disease, since both are hampered by conflicting data. Finally, there is growing appreciation that IBS can present in patients with known but stable organic gastrointestinal diseases, such as quiescent IBD or coeliac disease. Recognising functional gut symptoms in these individuals is paramount so that potentially harmful escalations in immunosuppressive therapy can be avoided and attention can be focused on addressing disorders of gut-brain interaction. This Review endeavours to aid clinicians who practise adult gastroenterology in recognising the potential overlap between IBS and organic gastrointestinal diseases and highlights areas in need of further research and clarity.

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