Liraglutide Efficacy and Action in Non-Alcoholic Steatohepatitis

• Status: Completed
• Trial end date: 2014-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to investigate whether 48 weeks treatment with once-daily injections of liraglutide improves liver disease (liver fat, inflammation and scarring) and related metabolic parameters in overweight patients with nonalcoholic steatohepatitis, enough to warrant further investigation.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Birmingham
• Collaborators: Novo Nordisk A/S; Wellcome Trust
• Treatments: Liraglutide

Criteria

Inclusion Criteria:

• NASH on liver biopsy (within 6 months of screening visit).

• NAFLD Activity Score (NAS) ≥ 3, comprising of a minimum of 1 point from each of the individual steatosis, lobular inflammation and hepatocyte ballooning scores

• Body Mass Index (BMI) ≥ 25 at randomisation

• Type 2 Diabetes Mellitus/impaired glucose tolerance or normal glucose tolerance

Exclusion Criteria (brief):

• Insulin dependent diabetes

• Glycosylated Haemoglobin (HbA1c) > 9.0%

• treatment with dipeptidyl peptidase 4 (DPP-IV) inhibitors, Glucagon-like Peptides (GLP) 1 analogues, thiazolidinediones (TZDs)

• Past Medical History of Acute (or chronic) pancreatitis/pancreatic carcinoma, weight loss surgery, liver transplantation, Medullary thyroid cancer, hepatocellular carcinoma (HCC), Multiple Endocrine Neoplasia (MEN) syndrome, malignancy (within last 3 years, exception of treated skin malignancy)

• Other liver aetiologies (i.e. drug-induced, viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, haemochromatosis, alpha 1 anti-trypsin deficiency, Wilsons disease)

• concomitant or recent use of orlistat, prednisolone,

• Refusal or lacks capacity to give informed consent to participate in the trial

• Participation in any clinical trial of an investigational therapy or agent within 3 months of randomisation

• 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

• NAS<3

• Child's B or C cirrhosis

• Abnormal clinical examination of thyroid (i.e. unexplained goitre or palpable nodules)

• Liver enzymes > 10 x upper limit of normal

• Average alcohol consumption per week > 21 units (210g) male, >14 units (140g) female within the last 5 years.

• >5% weight loss since the diagnostic liver biopsy was obtained.

• Recent or concomitant use of steroids (oral), methotrexate, amiodarone, Orlistat

• Addition or significant change (as judged by the chief investigator) in dose of the following drugs; Angiotensin converting enzymes (ACE)-inhibitors, Angiotensin receptor blockers (ARBs) and/or Multi-vitamins (containing Vitamin E)

• Known positivity for antibody to Human Immunodeficiency virus (HIV)

• Serum creatinine > 150 μmol/L or currently being treated with renal replacement therapy

• Past medical history of multiple drug allergies (defined as anaphylactoid drug reactions in >2 drug groups)

• 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

• Pregnancy or breastfeeding

• Women, of child-bearing age, who are not willing to practise effective contraception (i.e. barrier, oral contraceptive pill, implanon or history hysterectomy) for the 48 week duration of the trial and for one-month after the last administration of the drug.

• 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.