E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with morbid obesity (MB) are investigated. MB is very frequently (90%) associated with non-alcoholic fatty liver disease (NAFLD) comprising a spectrum reaching from steatosis (NAFL) over steatohepatitis (NASH) to fibrosis/cirrhosis. |
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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 | 10029530 |
E.1.2 | Term | Non-alcoholic fatty liver |
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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 |
Ursodeoxycholic acid (UDCA) improves clinical and biochemical serum parameters in a variety of cholestatic liver diseases. The efficacy of UDCA treatment in non-alcoholic fatty liver disease (NAFLD) has been debated and the mechanism(s) of action in humans are still not defined. However, UDCA may may improve insulin resistance and steatosis, as previously shown in mice. We aim to determine whether • UDCA (20mg/kg/d) improves insulin resistance in patients with NAFLD • UDCA improves hepatobiliary transporter expression in NAFLD • UDCA alters hepatic and/or white adipose tissue (WAT) lipase activity and fatty acid/triglyceride (FA/TG) content in NAFLD
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E.2.2 | Secondary objectives of the trial |
• Hepatic steatosis results in impaired expression of hepatobiliary ABC transporters and regulatory nuclear receptors contributing to liver damage and impaired bile acid flux/signalling in NAFLD • Hepatic and/or visceral white adipose tissue (WAT) lipase activity determines fatty acid (FA) release/balance from lipid triglyceride (TG) droplets and FA-mediated lipotoxicity in NAFLD; differences in hepatic and/or WAT activity could explain individual susceptibility to pure NAFL versus steatohepatitis (NASH).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Morbidly obese (BMI >35 kg/m2) patients of both gender scheduled for bariatric surgery. |
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E.4 | Principal exclusion criteria |
Any condition that does not allow bariatric surgery, i.e. major cardiovascular, liver or kidney disease, pregnancy, drug abuse. Insulin-dependent or independent diabetes mellitus. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Molecular characterization of ABC transporter expression and bile acid synthetic/metabolic enzymes in patients with different degrees of NAFLD (NAFL vs NASH).
2) Molecular expression of fatty acid synthetic/metabolism enzymes, hepatic lipase activity.
3) To study the impact of UDCA on expression and activity of fatty acid synthetic/metabolism enzymes, ABC transporter expression, regulatory nuclear receptor activity (FXR, PXR, CAR) and FGF 19, hepatic lipase activity, insulin resistance (HOMA), hepatic insulin signaling (IRS), ER stress (PERK, XBP-1).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | No |
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 | No |
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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Last visit of the last subject undergoing the trial. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |