Omegaven® in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the omega-3 fatty acid emulsion (Omegaven®), when used in place of the conventional soy-based fat emulsion (Intralipid), is effective in treating parenteral nutrition associated liver disease (PNALD) in children. The study hypothesis is that Omegaven® can be safely provided to children who are dependent on parenteral nutrition and have PNALD, and can reverse or prevent progression of PNALD until the child can take adequate nutrition by mouth.

Detailed Description
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Rationale for Omegaven® Treatment Unlike conventional intravenous fat emulsions, Omegaven® is comprised solely of fish oils containing primarily omega-3 fatty acids. Animal studies have shown that IV lipid emulsions such as fish oil that are high in eicosapentaenic and docosahexaenoic acid reduce impairment of bile flow as seen in cholestasis caused by conventional fat emulsions(1,2). By administering Omegaven® in place of conventional phytosterol/soybean fat emulsions, the cholestasis may be reversed and patients will be able to be maintained on adequate PN until they are able to ingest adequate nutrition enterally. References Chen W. Effects of fat emulsions with different fatty acid composition on plasma and hepatic lipids in rats receiving total parenteral nutrition. Clinical Nutrition 1996;15:24. Yeh S. Effects of fish oil and safflower oil emulsions on diet-induced hepatic steatosis in rats receiving total parenteral nutrition. Clinical Nutrition 1996;15:80.

Official Title
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Use of a Fish Oil-Based Intravenous Lipid Emulsion (Omegaven®) in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury

Conditions
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Total Parenteral Nutrition-induced Cholestasis

Intervention / Treatment
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* Drug: Omegaven®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children 0-18 years of age Patients will be PN-dependent and expected to continue PN for at least 30 days Patients considered eligible for study participation must have PN-associated liver diseases . Other causes of liver disease (i.e., biliary atresia, galactosemia, alpha-1 antitrypsin deficiency) will be excluded. A liver biopsy is not necessary for treatment Direct bilirubin > 2.0 mg/dl Signed patient informed consent Signed patient assent where applicable. Exclusion Criteria: Pregnancy Other causes of chronic liver disease (cystic fibrosis, biliary atresia, alpha-1 antitrypsin deficiency) Signs of advanced liver disease including cirrhosis on biopsy, varices, ascites The patient is allergic to eggs/shellfish The patient has a severe hemorrhagic disorder The patient is enrolled in any other clinical trial involving an investigational agent (unless approved by the designated physicians on the multidisciplinary team) The parent or guardian or child unwilling to provide consent or assent.

Ages Eligible for Study
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Minimum Age: 4 Weeks
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single Arm<br>Single Omegaven® Intervention Arm | Drug: Omegaven®<br>* 10% Omegaven® initiated at a starting dose of 0.5g/kg/day for two days and then advancing to the goal dose of 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated.<br>* Other names: IV Fish Oil Based Lipid Emulsion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Normalization of Direct Bilirubin | Normalization of direct bilirubin is defined as less than 0.4mg/dL by 9 months. This relates to the efficacy of parenteral administration of fish oil derived fat emulsion (Omegaven®) to reverse established parenteral nutrition associated liver disease. | Month 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Normal Essential Fatty Acid (EFA) Profiles. | EFA is defined at a triene tetraene ratio of greater than 0.2 (so normal is > 0.2). Collected monthly from month 1-9. | Months 1 through 9 | 
| Number of Participants With Triglyceride Levels > 400 mg/dL | Number of participants with triglyceride levels > 400 mg/dL | baseline data and then weekly and monthly evaluations, for an average of 9 months | 
| Number of Participants With Unexpected Bleeding or Coagulopathies |  | Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PNALD, Cholestasis, Omegaven®, Short Bowel Syndrome