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Omegaven Treatment of Parenteral Nutrition (PN) Induced Liver Injury

This study is currently recruiting participants.
Verified July 2011 by Children's Hospital Los Angeles
Sponsor:
Information provided by:
Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT01089426
First received: March 15, 2010
Last updated: July 22, 2011
Last verified: July 2011
History of Changes
  Purpose

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.


Condition Intervention
Liver Injury
 Drug: Omegaven™
Other: Historical Controls

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Research Study of an Intravenous Fat Emulsion Comprised of Fish Oils (Omegaven) in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Children's Hospital Los Angeles:

Primary Outcome Measures:
  • Rate of reduction of direct bilirubin [ Time Frame: normalization of direct bilirubin: an expected average of approximately 5 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: September 2008
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Highly refined fish oil for intravenous administration (10% Omegaven™)

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01089426

Contacts
Contact: Russell Merritt, M.D., PhD (323) 361-2181
Contact: Pui Yan, MSCR (323) 361-8631 pyan@chla.usc.edu

Locations
United States, California
Childrens Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027-6016
Contact: Russell Merritt, M.D., PhD     323-361-2181        
Contact: Pui Yan, MSCR     (323) 361-8631        
Principal Investigator: Russell Merritt, M.D., PhD.            
Sponsors and Collaborators
Children's Hospital Los Angeles
Investigators
Principal Investigator: Russell Merritt, M.D., PhD Children's Hospital Los Angeles
  More Information

Publications:

Responsible Party: Russell J. Merritt, MD, PhD, Intestinal Rehabilitation, GI Division, Childrens Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT01089426     History of Changes
Other Study ID Numbers: CCI-08-00127
Study First Received: March 15, 2010
Last Updated: July 22, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Los Angeles:
Pediatric patients with Parenteral Nutrition (PN) induced Liver Injury

ClinicalTrials.gov processed this record on May 22, 2013