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The Effect of n-3 Polyunsaturated Fatty Acid Supplements in Patients With Non-alcoholic Fatty Liver Disease

Primary Purpose

Non-alcoholic Fatty Liver Disease

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Efamax
Sponsored by
University of Nottingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-alcoholic Fatty Liver Disease focused on measuring Non-alcoholic fatty liver disease, Polyunsaturated fatty acids, Omega-3

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Wolfson Digestive Diseases Centre, University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

polyunsaturated

monounsaturated

Arm Description

5g per day of polyunsaturated fatty acids (3.5g EPA and DHA).

5g a day of oleic enriched sunflower oil

Outcomes

Primary Outcome Measures

Reduction of intrahepatic fat content as determined by magnetic resonance spectroscopy

Secondary Outcome Measures

Serum liver function tests, lipids, free fatty acids
Insulin resistance as assessed by HOMA-IR and Adipose Tissue Insulin Resistance Index
Liver saturated, monounsaturated and polyunsaturated fatty acid indexes as assessed by MR spectroscopy
Visceral obesity as quantified by MRI, and the adipose derived serum leptin and adiponectin
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
Further informative cytokine analyses: GM-CSF, IFN-G, IL-1B, IL-1RA, IL-2, IL-4, IL-5, MCP1
Compliance assessed by serum phospholipid fatty acids

Full Information

First Posted
January 8, 2009
Last Updated
July 3, 2012
Sponsor
University of Nottingham
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1. Study Identification

Unique Protocol Identification Number
NCT00819338
Brief Title
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

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Nottingham

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Fatty Liver Disease
Keywords
Non-alcoholic fatty liver disease, Polyunsaturated fatty acids, Omega-3

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
polyunsaturated
Arm Type
Active Comparator
Arm Description
5g per day of polyunsaturated fatty acids (3.5g EPA and DHA).
Arm Title
monounsaturated
Arm Type
Placebo Comparator
Arm Description
5g a day of oleic enriched sunflower oil
Intervention Type
Dietary Supplement
Intervention Name(s)
Efamax
Other Intervention Name(s)
oleic enriched sunflower oil
Intervention Description
5g daily as capsules for 3 months
Primary Outcome Measure Information:
Title
Reduction of intrahepatic fat content as determined by magnetic resonance spectroscopy
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Serum liver function tests, lipids, free fatty acids
Time Frame
3 months
Title
Insulin resistance as assessed by HOMA-IR and Adipose Tissue Insulin Resistance Index
Time Frame
3 months
Title
Liver saturated, monounsaturated and polyunsaturated fatty acid indexes as assessed by MR spectroscopy
Time Frame
3 months
Title
Visceral obesity as quantified by MRI, and the adipose derived serum leptin and adiponectin
Time Frame
3 months
Title
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
Time Frame
3 months
Title
Further informative cytokine analyses: GM-CSF, IFN-G, IL-1B, IL-1RA, IL-2, IL-4, IL-5, MCP1
Time Frame
3 months
Title
Compliance assessed by serum phospholipid fatty acids
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age greater than 18 years Liver biopsy diagnosis of NAFLD Exclusion Criteria: Excessive alcohol intake - > 21 units per week in men and > 14 in women A further liver disease diagnosis Poorly controlled diabetes - HbA1c > 8.0%, or use of insulin sensitisers Pregnancy Cirrhosis Contraindications to MR scanning - pacemaker or metallic foreign body etc. Changes in the dose or initiation of lipid altering medication within the preceding three months, such as statins, fibrates or systemic steroids Use of n-3 PUFA supplements within the prior 4 months, an adequate washout period Significant co-morbid inflammatory illnesses as determined by research team
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian A Macdonald, PhD
Organizational Affiliation
Biomedical Sciences, University Hospital, Nottingham
Official's Role
Study Chair
Facility Information:
Facility Name
Wolfson Digestive Diseases Centre, University Hospital
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom

12. IPD Sharing Statement

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The Effect of n-3 Polyunsaturated Fatty Acid Supplements in Patients With Non-alcoholic Fatty Liver Disease

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