Liraglutide Efficacy and Action in Non-Alcoholic Steatohepatitis (LEAN)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Wellcome Trust
Novo Nordisk A/S
Information provided by (Responsible Party):
Matthew Armstrong, University of Birmingham
ClinicalTrials.gov Identifier:
NCT01237119
First received: November 8, 2010
Last updated: October 10, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Nonalcoholic Steatohepatitis
Drug: Liraglutide
Other: Liraglutide-placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 48-week Phase II, Randomised, Double Blinded Placebo Controlled Multicentre Trial on Liraglutide's Safety, Efficacy and Action on Liver Histology and Metabolism in Overweight Patients With NASH +/- Type II Diabetes

Resource links provided by NLM:


Further study details as provided by University of Birmingham:

Primary Outcome Measures:
  • Liver Histological improvement [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • NAFLD Activity Score [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

    Also including:

    Fibrosis panel, Liver Function Tests (LFTs), cytokeratin-18 (CK-18) Glycaemic control, Fibroscan, Quality of life



Enrollment: 52
Study Start Date: August 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Liraglutide
A once-daily glucagon-like peptide 1 (GLP-1) analogue. Currently has regulation approval for use in type 2 diabetics (ref: guidelines)
Drug: Liraglutide
1.8 mg once daily, subcutaneous injection
Other Name: Victoza
Placebo Comparator: Placebo
Liraglutide-Placebo manufactured by Novo Nordisk.
Other: Liraglutide-placebo
1.8 mg once-daily, subcutaneous injection

Detailed Description:

Non-alcoholic fatty liver disease (NAFLD) is responsible for an increasing prevalence of liver disease and is becoming the commonest cause of liver disease in the western world. NAFLD is recognised to be the hepatic manifestation of the metabolic syndrome, which is a cluster of metabolic abnormalities characterised by abdominal obesity, insulin resistance, impaired glucose metabolism, hypertension and dyslipidaemia. In its mildest form there is an accumulation of fat in the liver (steatosis) without any liver damage, however in many cases it progresses to non-alcoholic steatohepatitis (NASH), and cirrhosis.

Current treatment options for NASH are limited in efficacy, necessitating the development of more effective options. New agents such as Glucagon-like Peptide-1 (GLP-1) agonists that improve diabetic control and facilitate weight loss have been suggested as therapies in NASH.

No published studies to date have assessed the impact of the GLP-1 agonist, Liraglutide, on liver histology and metabolism in obese patients with NASH. This study hypothesises that treatment with liraglutide will result in a significant improvement in histological disease activity in overweight patients with NASH, in the presence or absence of Type 2 Diabetes (T2DM)

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01237119

Locations
United Kingdom
NIHR BRU Centre for liver research, Queens Elizabeth University Hospital Birmingham
Birmingham, West Midlands, United Kingdom, B152TT
Sponsors and Collaborators
University of Birmingham
Wellcome Trust
Novo Nordisk A/S
Investigators
Principal Investigator: Philip N Newsome, FRCPE PhD Centre for liver research, University of Birmingham
  More Information

No publications provided

Responsible Party: Matthew Armstrong, Dr Matthew Armstrong, University of Birmingham
ClinicalTrials.gov Identifier: NCT01237119     History of Changes
Other Study ID Numbers: HE2013, ISRCTN85774727
Study First Received: November 8, 2010
Last Updated: October 10, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Liraglutide
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 18, 2014