New class of drugs shows promise in treating chronic diarrhea

October 20, 2014

A pilot study testing a new type of drug in patients with chronic diarrhoea has shown promising effects on reducing their symptoms.

Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea that is estimated to affect one in 100 adults in western countries, but is often mistaken for irritable bowel syndrome (IBS) by doctors. Many patients are not diagnosed correctly and undergo repeated unnecessary tests.

The study at Imperial College London found that the drug obeticholic acid (OCA) could provide relief for patients with BAD. OCA is the first in a new class of drugs, farnesoid X receptor (FXR) agonists, and the response of the patients to OCA shows that abnormalities in the system it targets may be critical for this condition. The research is published today in the journal Alimentary Pharmacology and Therapeutics.

Professor Julian Walters, from the Department of Medicine at Imperial College London, who led the study, said: "Many doctors are totally unaware of bile acid diarrhoea, but it's more common than Crohn's disease and ulcerative colitis. When patients are correctly diagnosed, there are specific treatments that can help them, but many people find these current drugs are unpalatable.

"The condition often has a serious impact on patients' work and social lives, causing people to have up to ten watery bowel movements a day, often for many months, with an urgent need to go to avoid accidental incontinence."

BAD is caused by excessive secretion of bile acids, a component of bile that aids digestion. After bile is secreted into the intestine from the gall bladder, the bile acids are normally absorbed in the ileum, a part of the small intestine. But in BAD, excess bile passes into the colon and causes watery diarrhoea.

A hormone produced in the ileum, FGF19, regulates the production of bile acids in the liver, and previous studies found that patients with BAD have low levels of FGF19. OCA targets the receptors in the ileum that stimulate the production of FGF19.

The researchers tested OCA in three groups of patients: 10 with primary BAD, where the intestine is otherwise healthy; 10 with secondary BAD, where malabsorption can occur as a result of another disease such as Crohn's; and eight with other causes of chronic diarrhoea, who served as a control group. The patients, who were treated at Imperial College Healthcare NHS Trust, recorded their symptoms in a diary for two weeks before starting OCA treatment, for two weeks taking the drug daily, and two weeks afterwards. They also had blood tests at the start and end of the OCA treatment period.

Symptoms improved with OCA treatment in the primary BAD patients and some secondary BAD patients, but not in those with other causes of chronic diarrhoea. The treatment was generally well tolerated.

Professor Walters added: "This drug represents a new potential approach to treating BAD by restoring the levels of the FGF19 hormone and so controlling bile acid production in the liver. These early findings suggest that FXR agonists could be effective for treating patients with chronic diarrhoea. This is exciting and we need larger studies to confirm this."
-end-
The study was carried out in collaboration with Intercept Pharmaceuticals, Inc. which is developing OCA for a variety of chronic liver diseases. It was funded in part by the Bardhan Research and Education Trust and by the Broad Medical Research Program.

For more information please contact:

Sam Wong
Research Media Officer
Imperial College London
Email: sam.wong@imperial.ac.uk
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248

Notes to editors:

1. Reference: J.R.F. Walters et al. 'The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid.' Aliment Pharmacol Ther, 20 October 2014. doi:10.1111/apt.12999 http://onlinelibrary.wiley.com/doi/10.1111/apt.12999/abstract

2. About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.

In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.

http://www.imperial.ac.uk

Imperial College London

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