Non-alcoholic steatohepatits (NASH) MedDRA version: 14.0 Level: PT Classification code 10012601 Term: Diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 14.0 Level: PT Classification code 10024670 Term: Liver disorder System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Trade Name: Victoza 6mg/ml
Product Name: Victoza (Liraglutide)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: LIRAGLUTIDE
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A 'Definite' diagnosis of Non-Alcoholic Steatohepatitis (NASH) on liver biopsy performed within 6 months of screening. 2. Age = 18 48 hours apart and/or Oral Glucose Tolerance Test (OGTT)): a. Impaired fasting glucose (IFG), defined using the European Criteria between 6.1 and 6.9 mmol/L AND/OR b.Impaired glucose tolerance (IGT), defined as two-hour plasma glucose levels between 7.8 and 11.0 mmol/ on the 75-g OGTT OR c. Normal Fasting Plasma Glucose (FPG) =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with a BMI > 45 kg/m2 2. Refusal or lacks capacity to give informed consent to participate in the trial 3. Participation in any clinical trial of an investigational therapy or agent within 3 months of randomisation 4. Patient (or carer) deemed not competent at using the correct site and technique for subcutaneous injection of the trial treatment (containing dummy drug on practice) at visit 2 5. Child’s Pugh stage B or C Liver cirrhosis 6. Past medical history of multiple drug allergies (>3 signficant drug allergies) 7. Presence of any acute/chronic infections or illness that at the discretion of the chief investigator might compromise the patient’s health and safety in the trial 8. Pregnancy or breastfeeding 9. Women, of child-bearing age, who are not willing to practise effective contraception for the 48 week duration of the trial and for one-month after the last administration of the drug. 10. Men, sexually active with women of child-bearing age, who are not willing to practise effective contraception for the 48 week duration of the trial and for one-month after the last administration of the drug. 11. Liver disease of other aetiologies (i.e. drug-induced, viral hepatitis, autoimmune hepatitis, PBC, PSC, harmochromatosis, A1AT deficiency, Wilsons disease) 12. Past medical/surgery history of;Gastric bypass surgery, Orthotopic liver transplant (OLT) or listed for OLT, Hepatocellular or pancreatic carcinoma, Acute or chronic pancreatitis, Total Parenteral Nutrition, within 6 months of randomisation. 13. Hepatocellular Carcinoma – dysplastic or intermediate nodules to be excluded. Borderline cases to be discussed at Birmingham’s tertiary hepato-biliary multidisciplinary team (MDT) meeting. Regenerative and other nodules to be included at the discretion of the chief investigator and the MDT. 14. Clinical evidence of decompensated chronic liver disease: o Radiological or clinical evidence of ascites o Current or previous hepatic encephalopathy o Evidence of portal hypertensive haemorrhage or varices on endoscopy 15. Malignancy within the last 3 years (with the exception of treated skin malignancies) 16. Abnormal clinical examination of thyroid (i.e. unexplained goitre or palpable nodules) 17. Blood levels of Alanine transaminase (ALT) or Aspartate Aminotransferase (AST) greater than 10 x upper limit of normal (local reference ranges will apply) 18. Average alcohol consumption per week > 21 units (168g) male, >14 units (112g) female within the last 5 years. 19. >5% weight loss between the diagnostic liver biopsy (preceding the study) and screening. 20. Recent or concomitant use of the following drugs within 6 months of randomisation; o Inducers of Hepatic steatosis - steroids, methotrexate, amiodarone, diltiazem o Weight-reducing therapies – Orlistat, Sibutramine 21. Addition or change in dose (as judged by the chief investigator) of the following drugs, within 6 months of randomisation; o Angiotensin converting enzymes (ACE)-inhibitors or Angiotensin receptor blockers (ARBs), Multi-vitamins (containg Vitamin E) 22. Known positivity for antibody to Human Immunodeficiency virus (HIV) 23. Serum creatinine > 150 µmol/L or Renal Replacement Therapy 25. Subjects with Type II Diabetes exclusion criteria (specific): • Current or previous insulin therapy, with exception of previous short-term insulin treatment in connection with intercurrent illness is allowed (= 3 months prior to screening), a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and efficacy of 48 weeks treatment with once-daily injections of liraglutide in damaged liver tissue in overweight patients with non-alcoholic steatohepatitis [NASH] (i.e. the more severe, inflammatory form of fatty liver disease). To investigate whether the effect of liraglutide on NASH warrants further investigation.;Secondary Objective: To investigate whether 48 weeks treatment with once-daily injections of liraglutide in overweight patients with non-alcoholic steatohepatitis effects the following, whilst maintaining the safety of the trial particpants: 1. reducing fat accumulation in the liver 2. reducing liver inflammation and scarring 3. reducing body weight, blood pressure, cholesterol and sugar levels (all of which are risk factors for heart disease, diabetes and increased risk of premature death) 4. improving the livers control of dangerous fats and high sugar levels in response to the hormone, insulin. 5. improving the patients nutrional intake and quality of life (analysed in questionnaire format);Primary end point(s): The primary objective is to investigate whether 48 weeks treatment with once-daily injections of liraglutide results in an improvement in liver histology in overweight patients with NASH. Both of the following criteria MUST be met in order to report an improvement in liver histology after treatment; • Disappearance of NASH (i.e. disappearance of hepatocyte ballooning) • No worsening in fibrosis stage (as defined by Kleiner et al, 2005) | — |
Countries
United Kingdom
Outcome results
None listed