Clinical trial NCT01845116: Omegaven® in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury
Official title: Use of a Fish Oil-Based Intravenous Lipid Emulsion (Omegaven®) in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Total Parenteral Nutrition-induced Cholestasis
Keywords: PNALD
Cholestasis
Omegaven®
Short Bowel Syndrome
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2013-05-03
Enrollment: 11
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Normalization of Direct Bilirubin
timeFrame: Month 9
Secondary outcomes:
measure: Number of Participants With Normal Essential Fatty Acid (EFA) Profiles.
timeFrame: Months 1 through 9
measure: Number of Participants With Triglyceride Levels > 400 mg/dL
timeFrame: baseline data and then weekly and monthly evaluations, for an average of 9 months
measure: Number of Participants With Unexpected Bleeding or Coagulopathies
timeFrame: Month 6
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Levine Children's Hospital at Carolinas HealthCare System
state: North Carolina
Study officials:
affiliation: Levine Children's Hospital at Carolinas HealthCare System
name: Ricardo A. Caicedo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.