(Patho)Physiological aspects of the bile salt-FXR-FGF19-axis: potential consequences in Crohn's disease. - Bile acid-FXR-FGF19 functioning in Crohn's disease

• Conditions: Patients with quiescent Crohn’s colitis, defined as a Crohn’s Disease Activity Index <150; non-IBD patients will serve as disease controls.; MedDRA version: 9.1Level: LLTClassification code 10011400Term: Crohn's colitis; MedDRA version: 9.1Level: LLTClassification code 10011401Term: Crohn's disease; MedDRA version: 9.1Level: LLTClassification code 10011402Term: Crohn's disease (colon)

• Registration Number: EUCTR2009-013348-35-NL
• Lead Sponsor: niversity Medical Center Utrecht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-03
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Patients with Crohn’s disease:
• Surveillance colonoscopy for established Crohn’s disease of the colon (indicated for clinical reasons)
• Informed consent of the patient.

Disease controls:
• A clinically indicated colonoscopy to exclude significant disease of the colon
• Informed consent of the patient

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients with Crohn’s disease:
• CDAI > 150 or frequency of defaecation > 4 / day
• Serum C-reactive protein >7
• Surgery of the gastro-intestinal tract (only appendectomy is allowed)
• Previous cholecystectomy
• Gallbladder or bile duct stones
• Previous ERCP with papillotomy.
• Age < 18 years
• Inability to communicate with the patient
• Body Mass Index > 25
• Concomitant primary sclerosing cholangitis or other significant hepatic or biliary pathology
• Any malignancy within 5 years before the study
• Clotting disorders: prolonged prothrombin time (PT) > 2.5 seconds increased compared to control or activated partial thromboplastin time (APTT) > 9 seconds increased compared to control (these values are considered within the normal range)
• Use of steroids, cyclosporine, methotrexate, anti-TNF compounds, antibiotics, loperamide/codeine or laxatives within one month before the study.
• Use of drugs, potentially interfering with CDCA (e.g. ursodeoxycholic acid or bile salt sequestrants), within one month before the study
• Pregnancy or lactation
• Liver function disorders: ASAT, ALAT, LDH, gGT and/or AF increased above ULN

Disease controls:
• Previous inflammation of the gastrointestinal tract (excluding previous infectious gastroenteritis if>6 months ago)
• Frequency of defaecation > 4 / day
• Serum C-reactive protein >7
• Surgery of the gastro-intestinal tract (only appendectomy is allowed)
• Previous cholecystectomy
• Gallbladder or bile duct stones
• Previous ERCP with papillotomy.
• Age < 18 years
• Inability to communicate with the patient
• Body Mass Index > 25
• Concomitant primary sclerosing cholangitis, or other significant hepatic or biliary pathology
• Any malignancy within 5 years before the study
• Clotting disorders: prolonged prothrombin time (PT) > 2.5 seconds increased compared to control or partial thromboplastin time (PTT) > 9 seconds compared to control (these values are considered normal)
• Use of steroids, cyclosporine, methotrexate, anti-TNF compounds, antibiotics, loperamide/codeine or laxatives within one month before the study
• Use of drugs, potentially interfering with CDCA (e.g. ursodeoxycholic acid or bile salt sequestrants), within one month before the study
• Pregnancy or lactation
• Liver function disorders: ASAT, ALAT, LDH, gGT, and/or AF increased above ULN

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To study potential abnormal functioning of the bile salt-FXR axis in patients with clinically quiescent Crohn’s colitis. We will employ in this study the potent FXR ligand chenodeoxycholic acid to stimulate this axis and use ileal and cecal biopsies for quantification of activation of FXR and its target genes. Also, plasma FGF 19 levels and gallbladder volumes will be used as parameters for FXR activation.;Secondary Objective: None.;Primary end point(s): Primary study endpoint is the difference between Crohn’s patients and disease controls in increase of fasting FGF19 level after 8 days chenodeoxycholic acid. ingestion.