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

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

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.

Study Overview

• Status: Completed
• Conditions: Total Parenteral Nutrition-induced Cholestasis
• Intervention / Treatment: Drug: Omegaven®

Detailed Description

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

1. 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.
2. 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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28232-2861
      • Levine Children's Hospital at Carolinas HealthCare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Single Arm; Single Omegaven® Intervention Arm	Drug: Omegaven®; 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.; Other Names: IV Fish Oil Based Lipid Emulsion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Ricardo A. Caicedo, MD, Levine Children's Hospital at Carolinas HealthCare System

Publications and helpful links

General Publications

• Puder M, Valim C, Meisel JA, Le HD, de Meijer VE, Robinson EM, Zhou J, Duggan C, Gura KM. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg. 2009 Sep;250(3):395-402. doi: 10.1097/SLA.0b013e3181b36657.
• Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR, Puder M. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics. 2006 Jul;118(1):e197-201. doi: 10.1542/peds.2005-2662.
• Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP, Arsenault DA, Strijbosch RA, Lopes S, Duggan C, Puder M. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008 Mar;121(3):e678-86. doi: 10.1542/peds.2007-2248.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2010
• Primary Completion (ACTUAL): July 1, 2020
• Study Completion (ACTUAL): July 1, 2020

Study Registration Dates

• First Submitted: April 29, 2013
• First Submitted That Met QC Criteria: May 1, 2013
• First Posted (ESTIMATE): May 3, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Cholestasis; PNALD; Short Bowel Syndrome; Omegaven®
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis
• Other Study ID Numbers: Omegaven 04-10-18B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Upon study completion

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No