E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with quiescent Crohn’s colitis, defined as a Crohn’s Disease Activity Index <150 ; non-IBD patients will serve as disease controls. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011400 |
E.1.2 | Term | Crohn's colitis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011402 |
E.1.2 | Term | Crohn's disease (colon) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Prospective case control study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
the same IMP (chenodeoxycholic acid) in non-Crohn's patients |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the last patient’s last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |