E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non alcoholic fatty liver disease (NAFLD). This fatty liver disease may progress to a chronic condition that sometimes deteriorates further to cirrhosis and even liver carcinoma. To date there is no licensed treatment for this condition and therefore it is important to test potential treatments for NAFLD. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031743 |
E.1.2 | Term | Other chronic nonalcoholic liver disease |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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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 |
The aim of our study is to phenotype 100 people with NAFLD, either biopsy-proven or confirmed by non-invasive imaging in a high-risk cohort (i.e. diabetic and/or features of the metabolic syndrome), and randomize subjects to treatment with purified n-3 fatty acids (OMACOR) 4 g / day or to placebo for 15-18 months.
The primary end-points of the study are: a) to assess change in serum biomarkers with treatment b) to measure changes in liver fat and validate changes in biomarkers with changes in liver fat |
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E.2.2 | Secondary objectives of the trial |
Secondary end-points of the study are:
a) to assess changes in measures of insulin sensitivity, microvascular function, carotid intima-media thickness, echocardiographic parameters, plasma cardiovascular risk markers, ankle brachial pressure index and pulse wave velocity and analysis (see below) with treatment.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. Effect of purified n-3 fatty acids (OMACOR) on hepatic insulin sensitivity in NAFLD (version 1).
In a sub-group of the study participants, we plan to undertake a pilot study to determine whether treatment with purified n-3 fatty acids (OMACOR) 4 g / day or placebo for 15-18 months with the objective of ascertaining whether OMACOR improves hepatic insulin sensitivity.
2. Hepatic fatty acid partitioning in NAFLD: the effect of n-3 fatty acids (OMACOR) (version 1).
In a subgroup of study participants, we will undertake a pilot study to investigate whether treatment with OMACOR 4g/day or placebo for 15-18 months, affects hepatic fat synthesis (hepatic de novo lipogenesis) and hepatic fat breakdown (oxidation). |
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E.3 | Principal inclusion criteria |
Inclusion criteria: 1. Steatohepatitis diagnosed on normal clinical grounds including in most cases liver biopsy and assessed by Kleiner scoring system to assess severity, with no known aetiological factors for underlying liver disease (e.g. exclusion of hepatitis A, B & C, primary biliary cirrhosis, autoimmune hepatitis, haemochromatosis).
2. Steatosis diagnosed by ultrasound, CT or magnetic resonance imaging who also have either diabetes and/or features of the metabolic syndrome, and without evidence of known aetiological factors for underlying liver disease (e.g. exclusion of hepatitis A, B & C, primary biliary cirrhosis, autoimmune hepatitis, haemochromatosis).
Liver biopsy or liver scan will be within 3 years of recruitment to the study.
Age: men & women >18 years. Alcohol consumption <35 units / week for women <50 units / week for men) .
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E.4 | Principal exclusion criteria |
Exclusion criteria: Decompensated acute or chronic liver disease, or harmful drinking (>35u/week in women >50 u /week in men). Pregnancy. Lactating women. Hypersensitivity to Omacor, soya or any of the excipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-points of the study are: a) to assess change in serum biomarkers with treatment b) to measure changes in liver fat and validate changes in biomarkers with changes in liver fat |
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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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Completion of 15-18 months treatment with either OMACOR or placebo and completion of last vist within 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 | 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 |