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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01051219
Recruitment Status : Completed
First Posted : January 18, 2010
Last Update Posted : October 7, 2015
Newcastle University
Information provided by (Responsible Party):
Newcastle-upon-Tyne Hospitals NHS Trust

Brief Summary:

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 or disease Intervention/treatment Phase
Nonalcoholic Steatohepatitis Drug: Losartan Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Controlled Trial of Losartan as an Anti-fibrotic Agent in Non-alcoholic Steatohepatitis
Study Start Date : May 2011
Actual Primary Completion Date : November 2014
Actual Study Completion Date : December 2014

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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) ]

Secondary Outcome Measures :
  1. Change in radiological (fibroscan) and serological (ELF) markers of fibrosis [ Time Frame: trial entry, 48 weeks, 96 weeks ]
  2. change in NAFLD activity score (NAS) [ Time Frame: trial entry, end of study ]
  3. comparison of "responder rate" - placebo versus intervention [ Time Frame: trial entry, end of study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 >15.0
  • 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
  • Introduction of metformin, glitazones, a GLP-1 agonist, Vitamin E or C, betaine, s-adenosyl methionine, ursodeoxycholic acid, silymarin, fibrate, pentoxifylline, orlistat, sibutramine or rimonabant within 3 months of baseline liver biopsy and screening visit
  • 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; pregelitanized maize starch; magnesium stearate [E572]; hydroxypropyl cellulose [E463]; hypromellose [E464])

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01051219

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United Kingdom
Plymouth Hospitals NHS Trust
Plymouth, Devon, United Kingdom, PL6 8DH
Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2TH
Cambridge University NHS Foundation Trust
Cambridge, United Kingdom, CB2 0QQ
Royal Derby Hospital
Derby, United Kingdom
Royal Liverpool & Broadgreen University Hospital
Liverpool, United Kingdom
Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom, SE1 7EH
Imperial College (St Mary's Site)
London, United Kingdom, SW7 2AZ
St George's Hospital
London, United Kingdom
Newcastle Upon Tyne Hospitals NHS Foundation Trust
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Queens Medical Centre
Nottingham, United Kingdom, NG7 2UH
Sponsors and Collaborators
Newcastle-upon-Tyne Hospitals NHS Trust
Newcastle University
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Study Chair: Christopher P Day, PhD Newcastle University
Study Director: Derek Mann, PhD Newcastle University
Study Director: Stephen F Stewart, PhD Newcastle University
Study Director: Elaine McColl, PhD Newcastle University
Study Director: Ian N Steen, PhD Newcastle University
Additional Information:

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Responsible Party: Newcastle-upon-Tyne Hospitals NHS Trust Identifier: NCT01051219    
Other Study ID Numbers: EME-08/43/15
ISRCTN ( Registry Identifier: 57849521 )
First Posted: January 18, 2010    Key Record Dates
Last Update Posted: October 7, 2015
Last Verified: October 2015
Keywords provided by Newcastle-upon-Tyne Hospitals NHS Trust:
Liver fibrosis
Nonalcoholic steatohepatitis
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action