Treatment of Non Alcoholic Fatty Liver Disease With n-3 Fatty Acids (WELCOME)

University Hospital Southampton NHS Foundation Trust

Status and phase: Completed; Phase 4

Conditions: Non-Alcoholic Fatty Liver Disease

Treatments: Drug: Placebo oral capsule; Drug: OMACOR

Study type: Interventional

Funder types: Other

Identifiers

NCT00760513

08/H0502/165 (Other Identifier)

25-12-59. (R&D: RHM MED 0836)

Details and patient eligibility

About

Non alcoholic fatty liver disease (NAFLD) imposes a high and increasing burden on the NHS, yet there is presently no licensed treatment or validated approach to management. NAFLD predisposes to increased risk of type 2 diabetes, increased risk of cardiovascular disease and may progress to chronic irreversible liver disease.

In NAFLD patients, the investigators will test the hypothesis that treatment with long chain n-3 fatty acid supplementation for 18 months favourably influences bio-markers for NAFLD and risk factors for cardiovascular disease and type 2 diabetes.

Full description

We will recruit people with NAFLD who have been diagnosed as part of their NHS care with having this condition. At present there is no treatment for this condition. Over time a proportion of people with NAFLD.

Purpose and design

We are asking the research question ' Does treatment with purified long chain n-3 fatty acids (purified fish oil) improve non alcoholic fatty liver disease and risk factors for heart disease and type 2 (adult) diabetes that are strongly linked to this liver condition?'

Presently there is no treatment for this liver condition. Research evidence suggests that purified long chain n-3 fatty acids might be beneficial for this condition.

To address this research question we want to undertake a randomised double blind placebo controlled trial recruiting people who have been diagnosed with a liver biopsy as having the liver condition.

A protocol change that were approved during in the course of the study in October 2011.

In the protocol, we have deleted information regarding liver biopsy that was to be offered at the end of the study.

Having collated volunteer opinion and local consultant opinion, whereas a high proportion of volunteers were happy to undergo a follow up liver biopsy, our local hepatologists now consider that in 2011, the small risk of morbidity and mortality of volunteers undergoing liver biopsy is unacceptable, within the context of a research study. Their opinions have changed since 2008 when the initial LREC approval was granted.

Liver biopsy was always an optional extra and would only have been undertaken in a subgroup of the volunteers. Therefore, removal of liver biopsy from the protocol does not affect the validity of the study to test effects of the n-3 fatty acid intervention on biomarkers and liver fat in people with non alcoholic fatty liver disease.

Besides removal of liver biopsy from the protocol, we have clarified in the protocol, the end points of the study and numbers randomised to either n-3 fatty acid or placebo (n=100, as always intended). We have also made it clear in the amendment that measurement of liver fat is also a primary outcome of the study. (We already have permission to undertake this test but it was uncertain when the study was approved that we would have sufficient funding for this expensive test and it was originally not a primary outcome).

We have therefore added a power calculation (and cited the relevant literature) to show that with a sample size of n=100 people, based upon the known treatment effects of n-3 fatty acids on liver fat, we have acceptable power to detect the predicted decrease in this outcome with treatment.

Enrollment: 103 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Steatohepatitis diagnosed on normal clinical grounds including in most cases liver biopsy and assessed by Kleiner scoring system to assess severity, with no known aetiological factors for underlying liver disease (e.g. exclusion of hepatitis A, B & C, primary biliary cirrhosis, autoimmune hepatitis, haemochromatosis).
2. Steatosis diagnosed by ultrasound, CT or magnetic resonance imaging who also have either diabetes and/or features of the metabolic syndrome, without evidence of known aetiological factors for underlying liver disease (e.g. exclusion of hepatitis A, B & C, primary biliary cirrhosis, autoimmune hepatitis, haemochromatosis).

Liver biopsy or liver scan will be within 3 years of recruitment to the study. Age: men & women >18 years. Alcohol consumption <35 units / week for women <50 units / week for men).

Exclusion criteria

• Decompensated acute or chronic liver disease, or harmful drinking (> 35 u/week in women > 50 u /week in men).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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103 participants in 2 patient groups, including a placebo group

Omega 3 fatty acid (fish oil)

Active Comparator group

Description:

OMACOR (alternative name: Lovaza) 4 grammes daily, oral capsule

Treatment:

Drug: OMACOR

dummy pill

Placebo Comparator group

Description:

4 grammes daily, oral capsule (olive oil)

Treatment:

Drug: Placebo oral capsule