CClinicalTrials.gg
Sign In
CompletedNCT01051219FELINEUpdated Oct 7, 2015

Anti-Fibrotic Effects of Losartan In Nash Evaluation Study

A Phase 3 interventional study of Losartan in Nonalcoholic Steatohepatitis, sponsored by Newcastle-upon-Tyne Hospitals NHS Trust. Completed at 10 sites in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-10-07.

Sponsored by Newcastle-upon-Tyne Hospitals NHS Trust · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
45
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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
02

Conditions studied

  • Nonalcoholic Steatohepatitis

Keywords

  • Losartan
  • Liver fibrosis
  • Nonalcoholic steatohepatitis
03

In context

Fatty Liver

1,451 studies on the registry are indexed under Fatty Liver; 292 are open to participants now.

This study's enrollment of 45 is below the median of 60 across 1,003 interventional studies indexed under Fatty Liver.

Browse Fatty Liver studies →

Lead sponsor

Newcastle-upon-Tyne Hospitals NHS Trust is the lead sponsor of 65 studies on the registry; 4 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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])
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
45 participants (actual)

Study arms

  • Active comparator
    Losartan, daily medication

    50 milligrams Losartan to be taken orally daily

    Drug: Losartan

  • Placebo comparator
    Placebo

    A matched placebo will be given for patients to take once daily

    Drug: Losartan

Interventions

  • DrugLosartan

    50 milligrams to be taken orally, daily

    Also known as: Losartan also known as Cozaar

06

What researchers measure

Primary outcomes

  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 outcomes

  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

07

Study locations

10 sites
  • Plymouth Hospitals NHS Trust
    Plymouth, Devon PL6 8DH, United Kingdom
  • Queen Elizabeth Hospital
    Birmingham, B15 2TH, United Kingdom
  • Cambridge University NHS Foundation Trust
    Cambridge, CB2 0QQ, United Kingdom
  • Royal Derby Hospital
    Derby, United Kingdom
  • Royal Liverpool & Broadgreen University Hospital
    Liverpool, United Kingdom
  • Guy's and St Thomas' NHS Foundation Trust
    London, SE1 7EH, United Kingdom
  • Imperial College (St Mary's Site)
    London, SW7 2AZ, United Kingdom
  • St George's Hospital
    London, United Kingdom
  • Newcastle Upon Tyne Hospitals NHS Foundation Trust
    Newcastle Upon Tyne, NE7 7DN, United Kingdom
  • Queens Medical Centre
    Nottingham, NG7 2UH, United Kingdom
08

References and documents

Publications

  • Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313-21. doi: 10.1002/hep.20701. PubMed 15915461 ↗
  • Newton JL, Jones DE, Henderson E, Kane L, Wilton K, Burt AD, Day CP. Fatigue in non-alcoholic fatty liver disease (NAFLD) is significant and associates with inactivity and excessive daytime sleepiness but not with liver disease severity or insulin resistance. Gut. 2008 Jun;57(6):807-13. doi: 10.1136/gut.2007.139303. Epub 2008 Feb 12. PubMed 18270241 ↗
  • Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, Lymp JF, Burgart L, Colin P. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004 Mar;39(3):770-8. doi: 10.1002/hep.20092. PubMed 14999696 ↗
  • Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol. 2005 Jan;42(1):132-8. doi: 10.1016/j.jhep.2004.09.012. PubMed 15629518 ↗
  • Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005 Jul;129(1):113-21. doi: 10.1053/j.gastro.2005.04.014. PubMed 16012941 ↗
  • Wright MC, Issa R, Smart DE, Trim N, Murray GI, Primrose JN, Arthur MJ, Iredale JP, Mann DA. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology. 2001 Sep;121(3):685-98. doi: 10.1053/gast.2001.27188. PubMed 11522753 ↗
  • Watson MR, Wallace K, Gieling RG, Manas DM, Jaffray E, Hay RT, Mann DA, Oakley F. NF-kappaB is a critical regulator of the survival of rodent and human hepatic myofibroblasts. J Hepatol. 2008 Apr;48(4):589-97. doi: 10.1016/j.jhep.2007.12.019. Epub 2008 Jan 31. PubMed 18279996 ↗
  • Oakley F, Meso M, Iredale JP, Green K, Marek CJ, Zhou X, May MJ, Millward-Sadler H, Wright MC, Mann DA. Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis. Gastroenterology. 2005 Jan;128(1):108-20. doi: 10.1053/j.gastro.2004.10.003. PubMed 15633128 ↗
  • Bataller R, Sancho-Bru P, Gines P, Lora JM, Al-Garawi A, Sole M, Colmenero J, Nicolas JM, Jimenez W, Weich N, Gutierrez-Ramos JC, Arroyo V, Rodes J. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology. 2003 Jul;125(1):117-25. doi: 10.1016/s0016-5085(03)00695-4. PubMed 12851877 ↗
  • Bataller R, Gabele E, Parsons CJ, Morris T, Yang L, Schoonhoven R, Brenner DA, Rippe RA. Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct-ligated rats. Hepatology. 2005 May;41(5):1046-55. doi: 10.1002/hep.20665. PubMed 15841463 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 7, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01051219
Lead sponsor
Newcastle-upon-Tyne Hospitals NHS Trust
Collaborators
Newcastle University
Responsible party
Sponsor
First posted
Jan 18, 2010
Start date
May 2011
Primary completion
Nov 2014
Completion
Dec 2014
Last update
Oct 7, 2015

Study contacts

Christopher P Day, PhD
study chair · Newcastle University
Derek Mann, PhD
study director · Newcastle University
Stephen F Stewart, PhD
study director · Newcastle University
Elaine McColl, PhD
study director · Newcastle University
Ian N Steen, PhD
study director · Newcastle University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2015. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Fatty Liver→

Other studies from this sponsor

Newcastle-upon-Tyne Hospitals NHS Trust

Start the discussion