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Fish Oil for Patients With Liver Disease Due to Parenteral Nutrition

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ClinicalTrials.gov Identifier: NCT01565278
Recruitment Status : Terminated (No more eligible patients could be identified.)
First Posted : March 28, 2012
Last Update Posted : May 12, 2016
Information provided by (Responsible Party):

Study Description
Brief Summary:
Patients who are not able to eat normally for a longer time require parenteral nutrition, i.e. they receive liquids and nutrients directly into their veins. This can have many long-term side effects, including liver problems. This study will examine whether a specific lipid emulsion containing fish oil can improve liver disease in patients on parenteral nutrition. The investigators will compare changes in bilirubin and liver enzymes after 3 months in 10 patients receiving standard lipid emulsion to 10 patients receiving standard lipids + a fish-oil containing emulsion. The investigators will also assess liver histology, the kind of fat, oxidative stress and gene expression in the liver at the beginning and after 6 months of fish-oil. The investigators also want to compare the baseline values from all 20 patients to 20 healthy controls. This will help to explain how fish oil may improve liver disease in patients on parenteral nutrition.

Condition or disease Intervention/treatment Phase
Total Parenteral Nutrition-induced Cholestasis Drug: Soybean oil (Standard treatment) Drug: Soybean oil + Fish oil Phase 3

Detailed Description:

Chronic exposure to total parenteral nutrition (TPN) can cause parenteral nutrition associated liver disease (PNALD), a progressive condition that may severely affect the liver and lead to end-stage liver disease. Fish oil has been shown to exert beneficial effects as it favorably alters metabolism and inflammation. It has been used parenterally (Omegaven) in young children with short bowel syndrome and PNALD with encouraging results. In adults it has mostly been used in peri-surgical settings as well as in critically ill patients, again proving its effectiveness.

The goal of this proposal is to show that Omegaven use in home-TPN patients with PNALD and elevated bilirubin despite conventional treatment, is beneficial in improving cholestasis and reducing intrahepatic inflammation. Primary objective is to compare the response to treatment between the Omegaven and the Intralipid group. Secondary objectives are to study the effect of Omegaven supplementation on single liver function tests, liver histology, liver fatty acid composition, liver oxidative stress and gene expression. In addition, the investigators want to compare the baseline values of all 20 patients to 20 healthy controls subjects.

After establishing that the patients' liver disease does not improve with conventional medical treatments for 3 months, as evidenced by repeated blood work at that time, they will all have a liver biopsy done as per diagnostic standards. They will then be randomized to either continue receiving Intralipid (0.25 g/kg/TPN day) or a mixture of Intralipid (0.25 g/kg/TPN day) and Omegaven (0.4 g/kg/TPN day) for a period of 3 months. After that, patients in the Omegaven arm will continue their treatment for 3 more months. Those in the Intralipid arm will be switched over to also receive Omegaven for the following 6 months.

Blood work will be repeated every 3 months after the initiation of the intervention. A repeat liver biopsy will be done in both groups after 6 months.

Main outcome is response to treatment (improvement in liver function tests) after 3 months (comparing Intralipid to Omegaven). In addition, change in liver function tests during the 6 months on Omegaven will be assessed. Lipid peroxidation and oxidative stress, fatty acid composition, and gene expression in the liver will be compared before and after 6 months on Omegaven.

In a second part of the study baseline values from all 20 patients will be compared to 20 healthy controls. Controls will be recruited from the healthy living liver donor transplant program at the University Health Network (UHN). Liver samples will be obtained at the time of hepatectomy for transplantation. The same measurements as for the patient livers will be performed in healthy liver tissue.

Significance: The investigators aim to reveal the beneficial effects of fish oil supplementation in the setting of PNALD. Should this pilot study show improvement in the liver disease with Omegaven, a larger, randomized trial should follow. Comparison with healthy controls will provide further insight into the pathogenesis of PNALD, which to date is not completely understood

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of n-3 Polyunsaturated Fatty Acid Lipid Emulsion on Parenteral Nutrition Associated Liver Disease
Study Start Date : February 2012
Primary Completion Date : August 2015
Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Soybean oil + Fish oil
Intralipid (0.25 g/kg/TPN day) + Omegaven (0.4 g/kg/TPN day) for a period of 6 months.
Drug: Soybean oil + Fish oil
Intralipid+Omegaven: 0.25 g/kg/TPN Intralipid day+0.4 g/kg/TPN Omegaven day for 6 months
Other Name: Intralipid, Omegaven
Active Comparator: Soybean oil (Standard treatment)
Standard treatment: Intralipid (0.25 g/kg/TPN day) for a period of 6 months
Drug: Soybean oil (Standard treatment)
1. Standard treatment: Soybean oil based emulsion: 0.25 g/kg/TPN day
Other Name: Intralipid

Outcome Measures

Primary Outcome Measures :
  1. Response to treatment at 3 months [ Time Frame: 3 months ]
    Response is defined as improvement of at least one PNALD parameter by 20% or more; PNALD parameters are: ALP, GGT, ALT, total bilirubin Yes/No

Secondary Outcome Measures :
  1. Change in total and conjugated bilirubin over time [ Time Frame: 0, 3, 6 months on Omegaven ]
  2. Changes in liver function test (ALP, AST, GGT) over 6 months [ Time Frame: 0, 3, 6 months on Omegaven ]
  3. Changes in liver histology between baseline and 6 months on Omegaven [ Time Frame: 0, 6 months on Omegaven ]
  4. Changes in liver fatty acid composition between baseline and 6 months on Omegaven [ Time Frame: 0, 6 months on Omegaven ]
    Fatty acid composition by gas chromatography

  5. Changes in liver oxidative stress between baseline and 6 months [ Time Frame: 0, 6 months ]
    Lipid peroxides in liver tissue (test-kit)

  6. Changes in hepatic gene expression between baseline and 6 months on Omegaven [ Time Frame: 0, 6 months on Omegaven ]
    Hepatic gene expression (mRNA) by microarray

Other Outcome Measures:
  1. Insulin resistance [ Time Frame: 0, 3, 6, 9 months ]
    HOMA-insulin resistance 0, 3, 6 months in Omegaven group 0, 3, 6, 9 months in Intralipid-group switching to Omegaven after 3 months

  2. Blood lipid profile [ Time Frame: 0, 3, 6, 9 months ]
    Triglycerides, total cholesterol, LDL, HDL 0, 3, 6 months in Omegaven group 0, 3, 6, 9 months in Intralipid-group switching to Omegaven after 3 months

  3. Complete blood count (CBC) [ Time Frame: 0, 3, 6, 9 months ]
    0, 3, 6 months in Omegaven group 0, 3, 6, 9 months in Intralipid-group switching to Omegaven after 3 months

  4. international normalized ratio (INR) [ Time Frame: 0, 3, 6, 9 months ]
    0, 3, 6 months in Omegaven group 0, 3, 6, 9 months in Intralipid-group switching to Omegaven

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Clinically stable patients on home TPN with PNALD with persistently elevated bilirubin (>1.5 times > normal) for at least 3 months despite standard treatment with ursodeoxycholic acid (15-30 mg/kg or at least 500 mg/d orally), changes in TPN (reduction to 25 kcal/kg/TPN day with Intralipid 0.25 g/kg) , and antibiotics (Metronidazole 500 mg bid and Ciprofloxacin 500 mg bid)
  • male or female,equal or over 18 years of age
  • on stable TPN regimen equal or over 3 days/week
  • on a stable drug regimen for equal or over 3 months prior to randomization, which will not changed for the study duration if these drugs are ursodeoxycholic acid given for PNALD or others affecting glucose and lipid metabolism

Exclusion Criteria:

  • Not receiving lipid emulsion as part of TPN
  • Allergy to fish, egg , soy, and peanuts
  • Liver disease of other etiology (e.g. excessive alcohol intake >20g/d, viral hepatitis, auto-immune or drug-induced, hemochromatosis, alfa 1-antitrypsin deficiency, Wilson's disease)
  • Complications of chronic liver disease, such as recurrent variceal bleeding, ascites, encephalopathy or any other reason contraindicating a liver biopsy
  • Severe hemorrhagic disorders
  • Sepsis - Inflammatory processes
  • Taking medications that precipitate steatohepatitis (e.g. corticosteroids, methotrexate, or amiodarone)
  • Pregnancy, lactation
  • Fluid restriction - Omegaven is more dilute than Intralipid.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01565278

Canada, Alberta
Foothills Medical Center
Calgary, Alberta, Canada, T2N 4Z6
University of Alberta
Edmonton, Alberta, Canada, T5H 3V9
Canada, Manitoba
St Boniface Hospital
Winnipeg, Manitoba, Canada, R2H 2A6
Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5G 2N2
Sponsors and Collaborators
Johane Allard
ASPEN Rhoads Research Foundation
Fresenius Kabi
University of Alberta
Foothills Medical Centre
St. Boniface General Hospital Research Centre
Hamilton Health Sciences Corporation
St. Paul's Hospital, Canada
Principal Investigator: Johane P Allard, MD,FRCPC University Health Network, Toronto
More Information


Responsible Party: Johane Allard, Professor of Medicine, Gastroenterologist, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01565278     History of Changes
Other Study ID Numbers: 11-0298-B
151342 ( Other Identifier: Health Canada NOL Control Number )
155516 ( Other Identifier: Health Canada Amendment control # )
161875 ( Other Identifier: Health Canada Amendment control # )
169378 ( Other Identifier: Health Canada Amendment control # )
First Posted: March 28, 2012    Key Record Dates
Last Update Posted: May 12, 2016
Last Verified: May 2016

Keywords provided by Johane Allard, University Health Network, Toronto:
Parenteral nutrition
fish oil
liver disease
liver biopsy

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases
Soybean oil, phospholipid emulsion
Fat Emulsions, Intravenous
Parenteral Nutrition Solutions
Pharmaceutical Solutions