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

Primary Purpose

Nonalcoholic Steatohepatitis

Status

Completed

Phase

Phase 3

Locations

United Kingdom

Study Type

Interventional

Intervention

Losartan

About this trial

This is an interventional treatment trial for Nonalcoholic Steatohepatitis focused on measuring Losartan, Liver fibrosis, Nonalcoholic steatohepatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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])

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Losartan, daily medication

Placebo

Arm Description

50 milligrams Losartan to be taken orally daily

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

Outcomes

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

Secondary Outcome Measures

Change in radiological (fibroscan) and serological (ELF) markers of fibrosis

change in NAFLD activity score (NAS)

comparison of "responder rate" - placebo versus intervention

Full Information

NCT ID

NCT01051219

First Posted

January 15, 2010

Last Updated

October 6, 2015

Sponsor

Newcastle-upon-Tyne Hospitals NHS Trust

Collaborators

Newcastle University

1. Study Identification

Unique Protocol Identification Number

NCT01051219

Brief Title

Anti-Fibrotic Effects of Losartan In Nash Evaluation Study

Acronym

FELINE

Official Title

A Randomised, Controlled Trial of Losartan as an Anti-fibrotic Agent in Non-alcoholic Steatohepatitis

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Completed

Study Start Date

May 2011 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Newcastle-upon-Tyne Hospitals NHS Trust

Collaborators

Newcastle University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nonalcoholic Steatohepatitis

Keywords

Losartan, Liver fibrosis, Nonalcoholic steatohepatitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Losartan, daily medication

Arm Type

Active Comparator

Arm Description

50 milligrams Losartan to be taken orally daily

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Losartan

Other Intervention Name(s)

Losartan also known as Cozaar

Intervention Description

50 milligrams to be taken orally, daily

Primary Outcome Measure Information:

Title

Time Frame

trial entry, end of study (2 years)

Secondary Outcome Measure Information:

Title

Change in radiological (fibroscan) and serological (ELF) markers of fibrosis

Time Frame

trial entry, 48 weeks, 96 weeks

Title

change in NAFLD activity score (NAS)

Time Frame

trial entry, end of study

Title

comparison of "responder rate" - placebo versus intervention

Time Frame

trial entry, end of study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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 >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])

Overall Study Officials: