Ursodeoxycholic acid in C. difficile infection
Research type
Research Study
Full title
Feasibility Studies to Investigate the Role of Ursodeoxycholic acid in the prevention of Recurrence of C.difficile Infection
IRAS ID
238106
Contact name
Yashwant Mahida
Contact email
Sponsor organisation
Nottingham University Hospitals NHS Trust
Eudract number
2018-001906-27
Duration of Study in the UK
1 years, 2 months, 1 days
Research summary
C. difficile infection remains a significant clinical problem in the UK and predominantly affects the elderly. The infection usually occurs when there is a reduction in the number of protective bacteria in the large bowel. Antibiotics, taken to treat other infections in other parts of the body (for example pneumonia), may also kill those bacteria in the large bowel that normally provide protection against C. difficile. Other antibiotics then used to treat the actual C. difficile infection may further reduce the number of protective bacteria in the large bowel. Despite initial treatment, about 25-30% of patients have a recurrence of C. difficile infection, which is usually treated with yet more antibiotics. Some patients may suffer from numerous recurrences of C. difficile infection, which can be difficult to treat. The infection can result in prolonged hospitalisation & hospital re-admissions and the difficulty is that treatment uses the same class of drugs (antibiotics) that created the environment for the initial problem in the first place. There is therefore a pressing need for non-antibiotic-based drugs for the treatment and prevention of C. difficile infection. Recent research has shown that the protective bacteria work by converting primary bile acids into secondary bile acids. The drug ursodeoxycholic acid is a secondary bile acid which has been widely used as a long-term treatment of some liver diseases. Our laboratory research has shown that ursodeoxycholic acid inhibits the growth of C. difficile and we now wish to determine whether taking ursodeoxycholic acid can prevent the recurrence of C. difficile infection. However, first we need to undertake pilot feasibility studies to determine whether ursodeoxycholic acid will be tolerated and acceptable to those patients who have recently been treated for C. difficile infection.
LAY SUMMARY OF STUDY RESULTS:
The purpose of this study was to initiate clinical research that aims to determine the role of ursodeoxycholic acid, which is a bile acid supplement, in providing protection against recurrence of C. difficile infection. Before embarking on a trial involving a large number of patients, feasibility studies are required to determine whether ursodeoxycholic acid will be tolerated and acceptable to those patients who have recently had C. difficile infection. The initial aim was to recruit thirty patients for the feasibility studies.
Unfortunately, the study had be terminated early after recruitment of 6 participants, for the following reasons: (i) there was major disruption related to COVID pandemic, (ii) there has been variation in the number of eligible cases of C. difficile infection, (iii) potential participants are predominantly frail elderly patients, with significant co-existing illnesses and most developed C. difficile infection during admission to hospital for another illness. Many of those eligible considered hospital study visits to be too burdensome.
Of the six patients that were recruited, three were able to tolerate gradually increasing doses of ursodeoxycholic acid over 6 weeks and there was no recurrence of C. difficile infection over the total 12 week study period. Three patients were able to tolerate low dose of ursodeoxycholic acid but developed predominantly gastrointestinal symptoms on the higher dose and therefore discontinued this bile acid supplement. These three patients had a history of relatively mild intermittent gastrointestinal symptoms prior to C. difficile infection. One of these latter patients had a recurrence of C. difficile infection 3 days after stopping ursodeoxycholic acid.
It is concluded that (i) the study plan enabled the identification of patients with varying levels of tolerance to ursodeoxycholic acid that was started within 7 days of completion of antibiotic treatment for C. difficile infection (ii) for future clinical investigation of the role of ursodeoxycholic acid in the prevention of recurrence of C. difficile infection, recruitment may be improved by undertaking study visits in the patient’s place of abode and (iii) history of gastrointestinal symptoms prior to C. difficile infection may predict lack of tolerance to higher doses of ursodeoxycholic acid.REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
18/WM/0239
Date of REC Opinion
28 Sep 2018
REC opinion
Further Information Favourable Opinion