Bile salt manipulation in Crohn's disease
| ISRCTN | ISRCTN77283008 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77283008 |
| Secondary identifying numbers | 08/0285 |
- Submission date
- 01/04/2009
- Registration date
- 08/04/2009
- Last edited
- 23/05/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Not provided at time of registration
Contact information
Dr Stuart Bloom
Scientific
Scientific
Department of Gastroenterology
Ground Floor Rosenheim Building
25 Grafton Way
London
WC1E 6DB
United Kingdom
Study information
| Study design | Single-centre open-label pilot study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Bile salt manipulation as a novel treatment for Crohn's disease: a single-centre open-label pilot study of atorvastatin and colesevalam in patients with active terminal ileal Crohn's disease |
| Study acronym | BISMAC |
| Study hypothesis | We hypothesise that the mucosal breaches and/or increased intestinal permeability may be caused by bile salts. Various in vitro, in vivo and biopsy studies have shown that bile salts can disrupt the intestinal mucosa and increase permeability, by loosening tight junctions, or inducing apoptosis of gut epithelial cells. Therefore, it is possible that bile salts contribute to intestinal barrier dysfunction, allowing ingress of antigenic material into the bowel wall. In a patient with impaired acute inflammation, as has been established to be the case in Crohns disease, this may act as the trigger for the development of small bowel Crohns disease. If bile salts are important in the pathophysiology of terminal ileal Crohns disease, then therapies that alter the composition of the bile salt pool may be of benefit. Statins (HMG CoA reductase inhibitors) are currently widely used in the treatment of cardiovascular disease. Their main mechanism of action is inhibition of cholesterol biosynthesis, although they also have pleiotropic effects such as immunomodulation. Cholestyramine is a bile acid binding resin used in the treatment of hyperlipidaemias, primary prevention of coronary heart disease, as well as in the treatment of bile salt malabsorption. It is also often used in patients with Crohns disease who have had bowel resection surgery to treat the diarrhoea that can occur as a result of bile salts irritating the colon. It has been demonstrated that combined administration of simvastatin and cholestyramine (at doses of 20 mg/day and 8 g/day respectively) results in a decreased concentration of duodenal bile salts, and that changes in bile salt composition occur after use of cholestyramine alone or in combination therapy. Use of these agents should therefore result in a reduction in bile salt concentration at the mucosal surface, thereby limiting damage to the mucosa and enabling healing. |
| Ethics approval(s) | Not provided at time of registration |
| Condition | Crohn's disease localised to the terminal ileum |
| Intervention | Atorvastatin 10 mg orally once daily plus Colesevelam 1875 mg orally twice daily taken for six weeks. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Atorvastatin, colesevelam |
| Primary outcome measure | Response, as defined by a 100 point fall in the Crohn's Disease Activity Index (CDAI) score at week 6 compared to baseline |
| Secondary outcome measures | 1. Remission (defined as an absolute Crohn's Disease Activity Index (CDAI) score of less than or equal to 150) at week 6 2. Mucosal healing (as defined by a faecal calprotectin level of less than or equal to 50 mg/kg) at week 6 3. Serum C-reactive protein level at week 6 compared with baseline |
| Overall study start date | 01/05/2009 |
| Overall study end date | 01/09/2009 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 13 |
| Participant inclusion criteria | 1. Able to give informed consent 2. Greater than 18 years of age, either sex 3. Diagnosis of Crohn's disease confined to the terminal ileum (but may involve the ileocaecal valve) 4. Mild to moderate disease activity, defined as a Crohn's Disease Activity Index (CDAI) score of 220 - 400 5. Negative SeHCAT scan within 6 months of enrolment into the study 6. Patients: 6.1. On no medication 6.2. Who have received aminosalicylates or nutritional supplements for at least 8 weeks prior to screening with no clinically relevant change in dose (as determined by the investigator) within 4 weeks 6.3. Are receiving immunosuppressants (except steroids) commenced at least 12 weeks prior to screening and been on a stable dose for at least 4 weeks 7. Able to comply with trial requirements (drug taking and visits) 8. Negative serum pregnancy test in females of child-bearing potential, who must agree to use an adequate method of contraception for the duration of trial 9. Stool sample negative for pathogenic bacteria and C. difficile toxin (if clinically indicated) during current episode of disease flare |
| Participant exclusion criteria | 1. Fasting triglyceride level greater than 3.4 mmol/L 2. Use of oral or parenteral steroids within four weeks or infliximab within eight weeks of start of trial medication; use of any investigational medication within the preceding 3 months 3. Use of antibiotics as treatment for the Crohn's disease within 4 weeks of screening 4. Current use of a 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase inhibitor or bile acid sequestrants, or use within 12 weeks of screening 5. Known intolerance to either HMG CoA reductase inhibitors or bile acid sequestrants 6. Taking any of the prohibited medications listed in protocol 7. Existing colostomy or ileostomy; current symptoms of bowel obstruction; any other severe concurrent morbidity including bleeding disorders or active upper gastrointestinal peptic ulceration; likely need for hospitalisation during the period of the study 8. Significant hepatic or renal dysfunction (alanine aminotransferase [ALT] greater than twice the upper limit of normal [ULN]; creatinine greater than 150 µmol/L) 9. Women who are currently or attempting to become pregnant, or those who are breast-feeding |
| Recruitment start date | 01/05/2009 |
| Recruitment end date | 01/09/2009 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University College London Hospitals
London
WC1E 6DB
United Kingdom
WC1E 6DB
United Kingdom
Sponsor information
University College London (UK)
University/education
University/education
Joint UCLH/UCL Biomedical research (R&D) Unit
Research & Development (1st Floor Maple House)
Ground Floor Rosenheim Building
25 Grafton Way
London
WC1E 6DB
England
United Kingdom
| Website | http://www.ucl.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Other
Investigator initiated and funded (UK) - University College London Hospital will not be charging for any routine care in this trial
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Editorial Notes
23/05/2016: No publications found, verifying study status with principal investigator.
