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Nonalcoholic SteatohepatitisPhase 2LEANNCT01237119

Liraglutide Efficacy and Action in Non-Alcoholic Steatohepatitis

A Phase 2 study testing Liraglutide in people with Nonalcoholic Steatohepatitis, run by University of Birmingham at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Nonalcoholic Steatohepatitis
What is being tested?
Liraglutide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
52 participants
Where
1 siteUnited Kingdom
Study dates
Aug 2010to Jul 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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,
Show all 24Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

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

    Birmingham, West Midlands, B152TT

Other trials in United Kingdom

About this study

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

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.

Read the 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)

Being tested
Liraglutide, Liraglutide-placebo
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LiraglutideDrug

    Also called Victoza

    1.8 mg once daily, subcutaneous injection

  • Liraglutide-placeboOther

    1.8 mg once-daily, subcutaneous injection

Study groups in NCT01237119
Study groupRoleWhat they receive
LiraglutideExperimentalA once-daily glucagon-like peptide 1 (GLP-1) analogue. Currently has regulation approval for use in type 2 diabetics (ref: guidelines)
Receives: Drug: Liraglutide
PlaceboPlacebo comparatorLiraglutide-Placebo manufactured by Novo Nordisk.
Receives: Other: Liraglutide-placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Liver Histological improvement

    Measured: 48 weeks

Secondary outcomes (1)

  1. NAFLD Activity Score

    Also including:

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

    Measured: 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2010 (estimated)
  2. Study startAug 2010
  3. Primary completionJul 2014
  4. Study completionJul 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01237119
Sponsor's protocol ID
HE2013
Other IDs
ISRCTN85774727
Acronym
LEAN
Status last verified
Mar 2016
First submitted
8 Nov 2010
Last updated
23 Mar 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 24189085

  • 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.

    PubMed 26608256

  • 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.

    PubMed 26394161

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Liraglutide in people with Nonalcoholic Steatohepatitis, run by University of Birmingham at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Liver Histological improvement (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01237119, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2016.

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