Liraglutide Efficacy and Action in Non-Alcoholic Steatohepatitis

NCT01237119 | Completed Phase 2 DMC

• 2 other identifiers: HE2013ISRCTN85774727
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Liver Histological improvement

  48 weeks

Secondary Outcomes (1)

• NAFLD Activity Score

  48 weeks

Study Arms (2)

Liraglutide

EXPERIMENTAL

A once-daily glucagon-like peptide 1 (GLP-1) analogue. Currently has regulation approval for use in type 2 diabetics (ref: guidelines)

Drug: Liraglutide

Placebo

PLACEBO COMPARATOR

Liraglutide-Placebo manufactured by Novo Nordisk.

Other: Liraglutide-placebo

Interventions

Liraglutide DRUG

1.8 mg once daily, subcutaneous injection

Also known as: Victoza

Liraglutide

Liraglutide-placebo OTHER

1.8 mg once-daily, subcutaneous injection

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Birmingham: lead
• Wellcome Trust: collaborator
• Novo Nordisk A/S: collaborator

Study Sites (1)

NIHR BRU Centre for liver research, Queens Elizabeth University Hospital Birmingham

Birmingham, West Midlands, B152TT, United Kingdom

Location

Related Publications (3)

• Armstrong MJ, Barton D, Gaunt P, Hull D, Guo K, Stocken D, Gough SC, Tomlinson JW, Brown RM, Hubscher SG, Newsome PN; LEAN trial team. Liraglutide efficacy and action in non-alcoholic steatohepatitis (LEAN): study protocol for a phase II multicentre, double-blinded, randomised, controlled trial. BMJ Open. 2013 Nov 4;3(11):e003995. doi: 10.1136/bmjopen-2013-003995.

  PMID: 24189085 BACKGROUND

• Armstrong MJ, Gaunt P, Aithal GP, Barton D, Hull D, Parker R, Hazlehurst JM, Guo K; LEAN trial team; Abouda G, Aldersley MA, Stocken D, Gough SC, Tomlinson JW, Brown RM, Hubscher SG, Newsome PN. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016 Feb 13;387(10019):679-690. doi: 10.1016/S0140-6736(15)00803-X. Epub 2015 Nov 20.

  PMID: 26608256 RESULT

• Armstrong MJ, Hull D, Guo K, Barton D, Hazlehurst JM, Gathercole LL, Nasiri M, Yu J, Gough SC, Newsome PN, Tomlinson JW. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis. J Hepatol. 2016 Feb;64(2):399-408. doi: 10.1016/j.jhep.2015.08.038. Epub 2015 Sep 21.

  PMID: 26394161 RESULT

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Philip N Newsome, FRCPE PhD

  Centre for liver research, University of Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2010
• First Posted: November 9, 2010
• Study Start: August 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: March 23, 2016

Record last verified: 2016-03

Locations

GB (1)