E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-alcoholic steatohepatitis (NASH) |
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E.1.1.1 | Medical condition in easily understood language |
Non-alcoholic fatty liver disease - fat and inflammation in the liver |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
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 determine if treatment with Liraglutide improves liver fat and inflammation (non-alcoholic steatohepatitis, NASH), more than matched weight loss alone |
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E.2.2 | Secondary objectives of the trial |
Investigate changes in: 1. the rate of hepatic de-novo lipogenesis (new fat generation and deposition in the liver) 2. circulating liver transaminases (liver function markers in the blood) 3. liver and peripheral insulin sensitivity and glucose disposal (metabolism) 4. adipose (fat) tissue insulin sensitivity 5. whole body fat oxidation 6. weight and BMI 7. body fat and muscle composition
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Non-diabetic (HbA1c <48mmol/mol) BMI 25-40kg/m2 Age 18-75years Diagnosis of NAFLD (hepatic steatosis on imaging or histology) ALT ≥ 1.5 ULN & <10 ULN on 2 occasions >7 days apart and or Historical liver biopsy showing NASH and/or ≥F1 fibrosis or NFS ≥ -1.455 OR Fib-4 ≥ 1.3 OR Fibroscan ≥8kPa. Non-pregnant, not planning pregnancy BP<160/100mmHg – stable antihypertensive therapy for 6 months No weight change >10% within the preceding 3 months Normal renal function No contraindications to Lifestyle or Liraglutide |
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E.4 | Principal exclusion criteria |
• Age <18 or >75years • Body mass index <25 or >40kg/m2 • A diagnosis of diabetes (type 1 or type 2) • Use of anti-diabetic or weight loss medications or a GLP-1 agonist such as Liraglutide) • Contra-indication to Liraglutide • A blood haemoglobin <120mg/dL • History of alcoholism or a greater than recommended alcohol intake (Recommendations > 21 drinks on average per week for men and > 14 drinks on average per week for women • Pregnant or nursing mothers • History of severe claustrophobia • Presence of metallic implants, pacemaker that are contra-indications to MRI scanning • Haemorrhagic disorders • Anticoagulant treatment • Other co-morbidities that in the eyes of the investigators may affect data collection • A medical condition in the opinion of the investigator that might impact upon safety or validity of the results |
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E.5 End points |
E.5.1 | Primary end point(s) |
Hepatic fat and inflammation measured using multi-parametric MR imaging (abdominal MRI) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change in rate of hepatic de-novo lipogenesis. Change in circulating liver transaminases. Change in hepatic and peripheral insulin sensitivity and glucose disposal. Change in adipose tissue insulin sensitivity. Change in whole body oxidation. Change in weight. Change in body composition. Change in urinary markers of liver disease. Change in faecal markers of liver disease. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | 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 | Information not present in EudraCT |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
Dietary and Lifestyle intervention |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | No |
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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LVLS (The end of study is the end of study day 3 at 24 weeks for the last participant) |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 1 |