Omegaven Treatment of Parenteral Nutrition (PN) Induced Liver Injury

May 2, 2019 updated by: Russell Merritt, Children's Hospital Los Angeles

Research Study of an Intravenous Fat Emulsion Comprised of Fish Oils (Omegaven) in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury

This study examines the hypothesis that administering intravenous fish oil, in lieu of intravenous soybean oil, can ameliorate the progression of PN-associated cholestatic liver disease in pediatric patients with elevated direct bilirubin requiring PN for more than 30 days.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In the United States, patients dependent upon parenteral nutrition (PN) receive parenteral fat emulsions composed of soybean oils. Lipids are necessary in PN dependent patients due to their high caloric value and essential fatty acid content. They have been implicated in predisposing patients to PN associated liver disease. Phytosterols such as those contained in soybean oils are thought to have a deleterious effect on biliary secretion.

Children requiring prolonged PN are at risk for developing PN associated liver disease. We hypothesize that although omega-6 fatty acid emulsions prevent fatty acid deficiency, they are not cleared in a manner similar to enteral chylomicrons and therefore accumulate in the liver and resulting in steatotic liver injury. We further hypothesize that a fat emulsion comprised of omega-3 fatty acids (i.e., fish oil) such as Omegaven™ would be beneficial in the management of steatotic liver injury by its inhibition of de novo lipogenesis, the reduction of arachidonic acid-derived inflammatory mediators, prevention of essential fatty acid deficiency through the presence of small amounts of arachidonic acid, and improved clearance of lipids from the serum. Animal studies have shown that IV fat emulsions (IFE) such as fish oil that are high in eicosapentaenic and docashexaaenoic acid reduce impairment of bile flow which is seen in cholestasis caused by conventional fat emulsions. Intravenous omega three fatty acids may be well tolerated and might reduce the inflammatory effect in the liver of prolonged PN exposure and could potentially reverse any hepatic dysfunction due to PN/IFE use. By administering Omegaven™ in place of conventional phytosterol/soybean fat emulsions we may reverse or prevent the progression of PN associated cholestasis and thus allow the patient to be maintained on adequate PN until they are able to ingest adequate nutrition enterally.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90027-6016
        • Childrens Hospital Los Angeles

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients will be parenteral nutrition dependent and are expected to require PN for at least another 30 days
  • Patients must have parenteral nutrition associated liver disease (PNALD) as defined by having at least 2 consecutive direct bilirubins >2 mg/dl.

Exclusion Criteria:

  • Pregnancy
  • Other causes of liver disease
  • Enrollment in any other clinical trial involving an investigational agent (unless approved by the designated physicians on the multidisciplinary team)
  • Direct bilirubin < 2 mg/dl
  • Allergy to any fish product, egg protein, and/or previous allergy to Omegaven
  • Active coagulopathy characterized by on-going bleeding or acute need for clotting factor replacement such as FFP or cryoprecipitate to maintain homeostasis
  • Impaired lipid metabolism as defined by serum Tg level >400 at time of initiation of Omegaven
  • Unstable diabetes mellitus
  • Recent stroke/embolism, not including catheter related thrombosis, which is a common complication of central venous catheter.
  • Collapse and shock
  • Undefined coma status
  • Untreated infection at time of initiation of Omegaven
  • Hemodynamic instability
  • > 21 years of age

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Historical controls
A subset of patients previously seen, who have had at least 2 consecutive direct bilirubin levels > 2 mg/dL, who depended on parenteral nutrition for at least 90 days after surgical therapy for congenital or acquired intestinal diseases
Other: Historical Controls
Standard of Care
Experimental: Omegaven™
Drug: Omegaven™
1 g/kg/d of Omegaven until discontinuation of PN
Other Names:
  • Highly refined fish oil for intravenous administration (10% Omegaven™)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate of reduction of direct bilirubin
Time Frame: normalization of direct bilirubin: an expected average of approximately 5 months
normalization of direct bilirubin: an expected average of approximately 5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Los Angeles

Investigators

  • Principal Investigator: Russell Merritt, M.D., PhD, Children's Hospital Los Angeles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

April 1, 2019

Study Completion (Actual)

April 1, 2019

Study Registration Dates

First Submitted

March 15, 2010

First Submitted That Met QC Criteria

March 17, 2010

First Posted (Estimate)

March 18, 2010

Study Record Updates

Last Update Posted (Actual)

May 6, 2019

Last Update Submitted That Met QC Criteria

May 2, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCI-08-00127

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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