Evaluation of Omegaven™ Parenteral Nutrition in Patients With Total Parenteral Nutrition (TPN)-Induced Cholestasis

Study Overview
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Brief Summary
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The purpose of this study is to determine if established parenteral nutrition (PN) associated liver disease can be reversed or its progression halted by using a parenteral fat emulsion prepared from fish oil as measured by normalization of serum levels of hepatic enzymes and bilirubin.

Detailed Description
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The primary objective of this study is to evaluate the need for and time to small bowel transplantation or liver transplantation. This will be calculated as both the age at time of primary transplant as well as the length of time from initial evaluation to transplant.Secondary objectives are to determine if there are improvements in clinical measures associated with established parenteral nutrition- associated liver disease (PNALD). These will be determined by measurement of total and direct bilirubin levels, platelet count, serum albumin, and changes in both length and weight growth curves.

Official Title
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Prospective Evaluation of a Parenteral Omega-3 Fatty Acid Preparation (Omegaven™) in Therapy of Patients With TPN-Induced Cholestasis

Conditions
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Cholestasis, Parenteral Nutrition Associated Liver Disease PNALD

Intervention / Treatment
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* Drug: Omegaven™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be enrolled in the Intestinal Rehabilitation Program at the University of Nebraska Medical Center, AND: Be unable to meet nutritional needs solely by enteral nutrition and be expected to require PN for at least another 30 days Have clinical evidence of parenteral nutrition associated liver disease (PNALD) as defined as a direct bilirubin of 2 mg/dl or more. A liver biopsy is desirable but not necessary for treatment Signed patient informed consent Exclusion Criteria: Parent or guardian or child unwilling to provide consent or assent Inability or unwillingness on the part of parent/guardian or child to follow clinical recommendations of the Intestinal Rehabilitation Program Allergies or clinical conditions precluding safe use of Omegaven™

Ages Eligible for Study
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Minimum Age: 19 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 |
| --- | --- |
| Experimental: Omegaven™<br>This study will be a prospective, non-randomized, open-label study of Omegaven™ for provision of parenteral lipid calories. The study cohort, receiving the parenteral nutrition (PN) lipid at 1g/kg/day, will be compared to historical controls at University of Nebraska Medical Center (UNMC) where parenteral lipid calories were provided exclusively through soybean-based formulations. The study is planned to enroll 100 patients. The Intestinal Rehabilitation Program at UNMC sees between 20 and 30 new pediatric patients per year, with almost all being PN-dependent and over 75% presenting with a bilirubin ≥ 2mg/dL. Based on these calculations, we estimate 4-5 years to enroll 100 patients. | Drug: Omegaven™<br>* 10% Omegaven™, 50 or 100 mL bottle; 1gram/kg/day and is infused over 12-24 hours.<br>* Other names: Omega-3 fat emulsion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Progression to Small Bowel Transplantation. | Whether or not the subject had an intestine-containing transplant or not | Bi-weekly x4, then monthly until the completion of the study, for an overall average of 5.5 years follow-up for the cohort | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Reversal of Biochemical Cholestasis | Of patients starting with elevated total serum bilirubin, the number that progress to normalization of serum total bilirubin in routine bloodwork | weekly x 4, then bi-weekly x4, then monthly until the completion of the study, with an average follow-up of 5.5 years for the study cohort | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PN, parenteral nutrition, fat emulsions, omega-6 fatty acid, liver disease, fatty acid deficiency