Clinical trial NCT00819338: The Effect of n-3 Polyunsaturated Fatty Acid Supplements in Patients With Non-alcoholic Fatty Liver Disease
Official title: The Effect of n-3 Polyunsaturated Fatty Acid Supplementation in Patients With Non-alcoholic Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-alcoholic Fatty Liver Disease
Keywords: Non-alcoholic fatty liver disease
Polyunsaturated fatty acids
Omega-3
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2009-01-09
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The principal purpose of this study is to determine whether increased intakes of n-3 polyunsaturated (omega-3) fatty acids will reduce the amount of fat stored in the liver in patients with non-alcoholic fatty liver disease.

Detailed description: Non-alcoholic fatty liver disease (NAFLD) is present in 10-24% of the general adult population. The first step of NAFLD involves the accumulation of fat within the liver (steatosis). Steatosis occurs either due to defective generation, metabolism or excretion of fatty acids by the liver. The next step in NAFLD progression is inflammation, which commonly occurs due to pro-inflammatory stimuli. Persistent inflammation results in end-stage liver disease. NAFLD is associated with the metabolic syndrome, which is characterised by central obesity, insulin resistance, raised triglycerides and hypertension. With the current obesity epidemic, there is predicted to be greater numbers of patients with NAFLD in the future.

Polyunsaturated fatty acids (PUFAs) are essential components of our diet, though standard Western intakes are lower than the recommended amounts. Supplementing the long chain n-3 PUFAs (commonly termed omega-3), EPA and DHA, improves many of the metabolic syndrome features. They lower plasma triglycerides, and may improve insulin resistance.

The diet of NAFLD patients tends to be deficient in n-3 PUFAs and have an excessive intake of the harmful n-6 PUFAs. This pattern is mirrored in their liver lipid content as assessed at biopsy.

Currently there is no proven treatment for NAFLD. Animal studies and limited studies in patients have been supportive of a benefit with n-3 polyunsaturated fatty acids. This needs to be further assessed.

Eligibility criteria: Inclusion Criteria:

1. Age greater than 18 years
2. Liver biopsy diagnosis of NAFLD

Exclusion Criteria:

1. Excessive alcohol intake - \> 21 units per week in men and \> 14 in women
2. A further liver disease diagnosis
3. Poorly controlled diabetes - HbA1c \> 8.0%, or use of insulin sensitisers
4. Pregnancy
5. Cirrhosis
6. Contraindications to MR scanning - pacemaker or metallic foreign body etc.
7. Changes in the dose or initiation of lipid altering medication within the preceding three months, such as statins, fibrates or systemic steroids
8. Use of n-3 PUFA supplements within the prior 4 months, an adequate washout period
9. Significant co-morbid inflammatory illnesses as determined by research team

Primary outcomes:
measure: Reduction of intrahepatic fat content as determined by magnetic resonance spectroscopy
timeFrame: 3 months
Secondary outcomes:
measure: Serum liver function tests, lipids, free fatty acids
timeFrame: 3 months
measure: Insulin resistance as assessed by HOMA-IR and Adipose Tissue Insulin Resistance Index
timeFrame: 3 months
measure: Liver saturated, monounsaturated and polyunsaturated fatty acid indexes as assessed by MR spectroscopy
timeFrame: 3 months
measure: Visceral obesity as quantified by MRI, and the adipose derived serum leptin and adiponectin
timeFrame: 3 months
measure: Primary assessment of the fibrotic and inflammatory status of the liver with serum TGF beta, TNF a, IL-6, IL-8, IL-8, IL-10
timeFrame: 3 months
measure: Further informative cytokine analyses: GM-CSF, IFN-G, IL-1B, IL-1RA, IL-2, IL-4, IL-5, MCP1
timeFrame: 3 months
measure: Compliance assessed by serum phospholipid fatty acids
timeFrame: 3 months
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Wolfson Digestive Diseases Centre, University Hospital
Study officials:
affiliation: Biomedical Sciences, University Hospital, Nottingham
name: Ian A Macdonald, PhD
role: STUDY_CHAIR
References: