Each patient download catalog gave written informed consent. The study was monitored by an independent external monitor. The study was registered at the Dutch Trial Register under number NTR2009 (www.trialregister.nl). Patients and protocol Patients with clinically quiescent CC (Harvey-Bradshaw Index (HBI) ��4)  and an indication for surveillance colonoscopy and disease controls who underwent colonoscopy for other clinical reasons were included if they consented in absence of exclusion criteria. Disease controls were excluded in case of previous inflammation of the gastrointestinal tract, with the exception of prior infectious gastroenteritis more than 6 months before the study.
Additional exclusion criteria for both groups were: stool frequency >4/day; Body Mass Index >30 kg/m2 (potential interference with ultrasonographic GB volume measurements); C-reactive protein (CRP) >20 mg/L within three months before the study, aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), gamma glutamyl transpeptidase (GGT) or alkaline phosphatase (ALP) above upper limit of normal within 3 months before the study, abnormal prothrombin time (PT) or activated partial thromboplastin time (APTT); prior surgery of the gastro-intestinal tract (except appendectomy); previous cholecystectomy or papillotomy; GB or bile duct stones; concomitant primary sclerosing cholangitis or other significant hepatic or biliary pathology; any malignancy within 5 years before the study; use of steroids, cyclosporine, methotrexate, anti-TNF compounds, antibiotics, loperamide or codeine, laxatives or other drugs potentially interfering with CDCA (e.
g. ursodeoxycholic acid or bile acid sequestrants) within one month before the study, and pregnancy or lactation. Four patients (three controls, one CC) were included in the study despite minimal increases of Alkaline Phosphatase (AF), gamma-glutamyltransferase (GGT) and APTT (resp. 2 U increase of AF in one patient, 2 U increase of GGT in another patient and 1 second increase of APTT in two patients), since these increases were thought not to lead to any safety concerns for these patients. Two included CC patients used oral anticoagulants and therefore APTT and PT were artificially increased during screening. For activation of FXR we used CDCA (15 mg/kg body weight; Tramedico, Weesp, the Netherlands; Sigma-tau, Dusseldorf, Germany), which is the most potent endogenous FXR ligand in man.
In contrast, the hydrophilic bile salt ursodeoxycholic acid (often used to treat cholestatic liver disease) has no effects on FXR activation. Anacetrapib To get an impression of the extent of FXR activation in the enterocyte during CDCA, we also included for comparison a small separate control group of patients who had colonoscopy but no CDCA pretreatment.