Treatment of Non Alcoholic Fatty Liver Disease With n-3 Fatty Acids
Condition: Non-Alcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed 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.
    

Intervention name(s): OMACOR; Placebo oral capsule
Intervention type(s): Drug; Drug
Intervention description(s): 4 grammes daily, oral capsule; 4 grammes daily, oral capsule (olive oil)
Other intervention name(s): Lovaza; Dummy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: non alcoholic fatty liver disease; NAFLD; fish oil; intervention; RCT; biomarkers