Losartan treatment for non-alcoholic steatohepatitis (NASH)

Plain English summary of protocol

Background and study aims
As many as 1 in 10 people have some form of liver disorder which can cause problems ranging from impaired quality of life to more serious complications including liver failure. Fibrosis is the accumulation of tough scar tissue in the liver, and occurs in patients with non-alcoholic steatohepatitis (NASH). The major feature of NASH is fat in the liver, along with inflammation and damage of the liver tissue. This can lead to permanent damage of the liver, which prevents it from functioning properly. Currently there are no available treatments aimed at slowing down or stopping the progression of fibrosis of the liver. Previous studies have demonstrated that drugs similar to Losartan help to reduce the inflammation. These studies would lead us to believe that Losartan will be effective in patients with NASH. This study aims to test Losartan in patients with fibrosis associated with NASH.

Who can participate?
Adults (both males and females, aged 18+) with fibrosis resulting from NASH.

What does the study involve?
Sometimes we need to find out how effective a study drug is by comparing two groups of patients with the same illness. We do this by giving the study tablet/capsule (Losartan) to one group and an identical looking tablet/capsule (the placebo), which contains inactive ingredients, to the other group. To try to make sure the groups are the same to start with, each patient is put into a group by chance (randomly – like tossing a coin). Neither you, your doctor, nor your spouse/family will know whether you are receiving Losartan or the placebo, as both will look exactly the same. We call this type of study a double-blind study. If your doctor needs to find out which treatment group you are in, then he or she may do so. You will take a study tablet/capsule once a day for up to two years. The study results will then be compared to see how effective the study drug is compared with the placebo. For the purposes of this study, you will attend your hospital outpatient department or research centre on nine occasions. On each of the nine occasions that you attend the hospital, your study assessment will take about 30 minutes, apart from your first visit which may take up to two hours. The assessments will be conducted by the research team, which includes a research doctor specializing in liver disease, as well as other trained research personnel. If you agree to be part of the study, you will be invited to sign the consent form before undergoing any research-related assessments. The sponsor of the study (Newcastle upon Tyne Hospitals NHS Foundation Trust) is currently in collaboration with GlaxoSmithKline who have requested the collection of extra blood samples to be collected at all of the visits, except visit three (week one). This will be explained to you by the Research Doctor, and you will be invited to participate in this separate voluntary study.

What are the possible benefits and risks of participating?
There may be no direct benefit to you from taking part. However, this study will help us to find out if Losartan is useful in slowing down, stopping or reversing liver fibrosis. We are unable to promise that the study will help you, but it may help patients in the future. There are no major disadvantages or risks in taking part in this study. Because we ask for some blood samples there is a small risk of bruising or discomfort at the injection site. A liver biopsy will be carried out at visit 8 (96 weeks). Up to one in three patients may experience some pain or discomfort following the biopsy. This may last two or three days. Usually a mild painkiller such as paracetamol is all that is need to treat this pain. Serious bleeding occurs in approximately one in 300 patients. This may require a blood transfusion or another procedure to stop it. Less than one in 1000 patients may have another organ punctured, such as lung, kidney or colon. This might cause pain or breathlessness, but would resolve itself without any further treatment. In less than one in 1000 patients, leakage of bile from the biopsy site into the abdomen may occur. This might cause pain in the abdomen but also usually resolves with no specific treatment. Patients with some conditions have an increased risk of infection after a liver biopsy. If we suspect that you have one of these conditions we will give you intravenous antibiotics before the biopsy. Slight discomfort may occur up to seven days after the biopsy, and you must inform your GP if this becomes severe or you develop swelling. Every effort will be made to keep you comfortable during this procedure. You will need to stay in hospital for six hours following the biopsy and possibly overnight after this procedure, but your doctor will discuss this with you prior to the procedure.

Where is the study run from?
Newcastle University (UK)

When is the study starting and how long is it expected to run for?
May 2011 to October 2014

Who is funding the study?
Medical Research Council (MRC)/National Institutes of Health Research (NIHR) (UK)

Who is the main contact?
Jessica Qian
jessica.qian@newcastle.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centres

Sponsor information

Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

Joint Research Office
Level 6
Leazes Wing
Royal Victoria Infrimary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
England
United Kingdom

Website	http://www.newcastle-hospitals.org.uk/about-us/staff-information_research-development.aspx
"ROR"	https://ror.org/05p40t847

Funders

Funder type

Government

Results and Publications

Study outputs

Editorial Notes

19/04/2017: Publication reference added.

16/06/2011: The following changes were made to the trial record:
1. The overall trial start date was changed from 01/01/2010 to 01/05/2011.
2. The overall trial end date was changed from 30/06/2013 to 01/10/2014.