Anti-Fibrotic Effects of Losartan In Nash Evaluation Study (FELINE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2011 by Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor:
Collaborators:
Newcastle University
University of Newcastle Upon-Tyne
Information provided by:
Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01051219
First received: January 15, 2010
Last updated: August 4, 2011
Last verified: February 2011
  Purpose

This is a randomized, controlled trial to determine whether Losartan is effective at slowing down, halting or reversing liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). Liver fibrosis is the accumulation of tough, fibrous scar tissue in the liver which occurs in patients with NASH. NASH resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage, which may lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to function properly.

Primary hypothesis:

That losartan is superior to placebo in reversing, slowing down or halting fibrosis in patients with non-alcoholic fatty liver disease, after 24 months of treatment.

Secondary hypothesis:

  1. That the safety profile of the angiotensin receptor blocker (losartan) in this patient population is acceptable
  2. That losartan can prevent clinical deterioration in non-alcoholic fatty liver disease
  3. That serum, radiological and histological markers of fibrosis correlate in these patients over a 24 month period

Condition Intervention Phase
Nonalcoholic Steatohepatitis
Drug: Losartan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Controlled Trial of Losartan as an Anti-fibrotic Agent in Non-alcoholic Steatohepatitis

Resource links provided by NLM:


Further study details as provided by Newcastle-upon-Tyne Hospitals NHS Trust:

Primary Outcome Measures:
  • The primary outcome will be change in Kleiner fibrosis score, [Kleiner DE et al Hepatology 2005], based on histological fibrosis stage (as judged by two independent blinded histopathologists from liver biopsies), from pre-treatment to end-of-study [ Time Frame: trial entry, end of study (2 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in radiological (fibroscan) and serological (ELF) markers of fibrosis [ Time Frame: trial entry, 48 weeks, 96 weeks ] [ Designated as safety issue: No ]
  • change in NAFLD activity score (NAS) [ Time Frame: trial entry, end of study ] [ Designated as safety issue: No ]
  • comparison of "responder rate" - placebo versus intervention [ Time Frame: trial entry, end of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 214
Study Start Date: May 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Losartan, daily medication
50 milligrams Losartan to be taken orally daily
Drug: Losartan
50 milligrams to be taken orally, daily
Other Name: Losartan also known as Cozaar
Placebo Comparator: Placebo
A matched placebo will be given for patients to take once daily
Drug: Losartan
50 milligrams to be taken orally, daily
Other Name: Losartan also known as Cozaar

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults (both males and females, aged 18+) with steatohepatitis and fibrosis (Kleiner F1-F3), resulting from non-alcoholic fatty liver disease.

Exclusion Criteria:

  • Refusal or inability (lack of capacity) to give informed consent
  • Average alcohol ingestion >21 units/week (males) or >14 units/week (females)
  • History or presence of Type 1 diabetes mellitus
  • Haemoglobin A1C >9.0
  • Other causes of chronic liver disease or hepatic steatosis
  • Any contra-indication to liver biopsy
  • History of, or planned, gastrointestinal bypass surgery
  • Hepatocellular carcinoma
  • Previous liver transplantation
  • Recent significant weight loss (>5% total body weight within last 6 months)
  • Electrolyte disturbance: potassium level outside the normal (local) range
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >10 x upper limit of normal (ULN) at screening
  • Recent (within 6 months of baseline liver biopsy and screening visit) or concomitant use of agent known to cause hepatic steatosis (corticosteroids, amiodarone, methotrexate, tamoxifen, tetracycline, high dose oestrogens, valproic acid), or concomitant use of pioglitazone, fluconazole, rifampicin or any drug contra-indicated in the Losartan SmPC
  • Recent (within 3 months of baseline liver biopsy and screening visit) change in anti-diabetes treatment or change in dose/regimen or introduction of Vitamin E or C, betaine, s-adenosyl methionine, ursodeoxycholic acid, silymarin, fibrate, pentoxifylline, orlistat, sibutramine or rimonabant
  • Intolerance of angiotensin receptor blockers (ARBs) or presence of multiple allergic reactions to drugs
  • Use of angiotensin-converting enzyme (ACE) inhibitor or ARB in previous year
  • Hypotension (systolic <100, diastolic <60)
  • Renal failure (Cr >130)
  • Participation in any clinical study of an investigational agent within 30 days or five half-lives of the investigational product, whichever is longer
  • Presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, haematological, neurological, psychiatric, systemic, ocular, gynaecologic or any acute infectious disease or signs of acute illness that, in the opinion of the investigator, might compromise the patient's safe participation in the trial
  • Presence or history of cancer within the past 5 years with exception of adequately treated localized basal cell carcinoma of the skin, in situ cervical carcinoma or solid malignancy surgically excised in toto without recurrence for five years
  • Women of child-bearing potential not protected by effective contraceptive method of birth control or surgical sterilization and/or who are unwilling or unable to be tested for pregnancy (Pregnancy status will be checked by serum pregnancy testing before initiation of study treatment and by urine pregnancy testing during the trial)
  • Known allergy or sensitivity to losartan or its excipients (microcrystalline cellulose [E460]; lactose monohydrate; pregelaatinized maize starch; magnesium stearate [E572]; hydroxypropyl cellulose [E463]; hypromellose [E464])
  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: NCT01051219

Contacts
Contact: Christopher P Day +44 (0)191 222 6755 c.p.day@ncl.ac.uk

Locations
United Kingdom
Plymouth Hospitals NHS Trust Not yet recruiting
Plymouth, Devon, United Kingdom, PL6 8DH
Contact: Tim Cross    +44 (0)1752 431278    tim.cross@phnt.swest.nhs.uk   
Contact: Linda March       linda.march@phnt.swest.nhs.uk   
Principal Investigator: Tim Cross         
Queen Elizabeth Hospital Not yet recruiting
Birmingham, United Kingdom, B15 2TH
Contact: Philip Newsome, PhD, FRCPE    +44(0)121 414-5614    P.N.Newsome@bham.ac.uk   
Contact: Jo Grayer       jo.grayer@uhb.nhs.uk   
Principal Investigator: Philip Newsome, PhD, FRCPE         
Cambridge University NHS Foundation Trust Not yet recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Mike Allison, BSc(Hons) MBBS MRCP PhD    +44(0)1223 586641    m.allison@addenbrookes.nhs.uk   
Contact: Julia Wilkinson       julia.wilkinson@addenbrookes.nhs.uk   
Principal Investigator: Michael Allison, BSc(Hons), MBBS, MRCP, PhD         
Guy's and St Thomas' NHS Foundation Trust Not yet recruiting
London, United Kingdom, SE1 7EH
Contact: Jude Oben, BM,BCh(Oxon),PhD,FRCP    +44(0)20-7188-7188 ext 82499    jude.oben@gstt.nhs.uk   
Contact: Susanne Johansen    +44(0)2071887188    Susanne.Johansen@gstt.nhs.uk   
Principal Investigator: Jude Oben, BM,BCh(Oxon),PhD,FRCP         
Imperial College (St Mary's Site) Not yet recruiting
London, United Kingdom, SW7 2AZ
Contact: Michael Yee, BSc, MBBS, MRCP, CCT    +44 (0)20 7886 6876    m.yee@imperial.ac.uk   
Contact: Claire Parsonage       c.parsonage@imperial.ac.uk   
Principal Investigator: Michael Yee, BSc, MBBS, MRCP, CCT         
Newcastle Upon Tyne Hospitals NHS Foundation Trust Recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Contact: Jane Barnes, RN, BA(Hons), MSc    +44(0)191 2227249    jane.barnes@ncl.ac.uk   
Principal Investigator: Stuart D McPherson, BSc(MedSci), MBChB, MRCP, MD         
Sub-Investigator: Mann Derek, BSc, PhD         
Sub-Investigator: Quentin M Anstee, BSc(Honours), MBBS, MRCP, PhD,         
Queens Medical Centre Not yet recruiting
Nottingham, United Kingdom, NG7 2UH
Contact: Guru Aithal, MD PhD FRCP    +44 (0)115 9249924 ext 65747    guru.aithal@nuh.nhs.uk   
Principal Investigator: Guruprasad P Aithal, MD PhD FRCP         
Sponsors and Collaborators
Newcastle-upon-Tyne Hospitals NHS Trust
Newcastle University
University of Newcastle Upon-Tyne
Investigators
Study Chair: Christopher P Day, MBBChir, BA, MD, PhD, FMedSci Newcastle University
Study Director: Derek Mann, BSc(Hons), PhD Newcastle University
Study Director: Stephen F Stewart, BSc, MBChB, MRCP, PhD Newcastle University
Study Director: Elaine McColl, BA(Hons), MSc, PhD Newcastle University
Study Director: Ian N Steen, BSc, MSc, PhD Newcastle University
  More Information

Additional Information:
Publications:

Responsible Party: Amanda Tortice, Research Operations Manager, Newcastle Upon Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01051219     History of Changes
Other Study ID Numbers: EME-08/43/15, ISRCTN
Study First Received: January 15, 2010
Last Updated: August 4, 2011
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Newcastle-upon-Tyne Hospitals NHS Trust:
Losartan
Liver fibrosis
Nonalcoholic steatohepatitis

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Losartan
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014