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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier:
NCT00760513
First received: September 25, 2008
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Non-Alcoholic Fatty Liver Disease
Drug: OMACOR
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: The Effects of Purified n-3 Fatty Acids on Serum Fibrosis Markers and Cardiovascular Risk Markers in a Randomized Placebo Controlled Trial in Patients With Non Alcoholic Fatty Liver Disease

Resource links provided by NLM:


Further study details as provided by University Hospital Southampton NHS Foundation Trust.:

Primary Outcome Measures:
  • Change in biomarkers for NAFLD and change in liver fat [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    The primary end-points of the study are: a) to assess change in serum biomarkers with treatment b) to validate changes in biomarkers with changes in Kleiner liver biopsy score in a sub-group of volunteers who opt for a follow-up liver biopsy and c) to validate changes in biomarkers with changes in liver fat measured by MR scan of liver for the whole study population.


Secondary Outcome Measures:
  • Change in risk factors for cardiovascular disease and type 2 diabetes [ Time Frame: 18 months ] [ Designated as safety issue: No ]

    Secondary end-points of the study are:

    a) to assess changes in measures of insulin sensitivity, microvascular function, carotid intima-media thickness, echocardiographic parameters, plasma cardiovascular risk markers, ankle brachial pressure index and pulse wave velocity and analysis (see below) with treatment.



Estimated Enrollment: 100
Study Start Date: November 2009
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Omega 3 fatty acid (fish oil)
OMACOR (alternative name: Lovaza) 4 grammes daily, oral capsule
Drug: OMACOR
4 grammes daily, oral capsule
Other Name: Lovaza
Placebo Comparator: dummy pill
4 grammes daily, oral capsule (olive oil)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00760513

Locations
United Kingdom
Southamption General Hospital
Southampton, Hants, United Kingdom, SO166YD
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust.
National Institute for Health Research, United Kingdom
  More Information

No publications provided by University Hospital Southampton NHS Foundation Trust.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier: NCT00760513     History of Changes
Other Study ID Numbers: 25-12-59. (R&D: RHM MED 0836), EudraCT number 2008-003766-26
Study First Received: September 25, 2008
Last Updated: February 28, 2014
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service

Keywords provided by University Hospital Southampton NHS Foundation Trust.:
non alcoholic fatty liver disease
NAFLD
fish oil
intervention
RCT
biomarkers

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on August 20, 2014