Clinical trial NCT00826020: Evaluation of Omegaven™ Parenteral Nutrition in Patients With Total Parenteral Nutrition (TPN)-Induced Cholestasis
Official title: Prospective Evaluation of a Parenteral Omega-3 Fatty Acid Preparation (Omegaven™) in Therapy of Patients With TPN-Induced Cholestasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parenteral Nutrition Associated Liver Disease PNALD
Cholestasis
Keywords: PN
parenteral nutrition
fat emulsions
omega-6 fatty acid
liver disease
fatty acid deficiency
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2009-01-21
Enrollment: 72
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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™

Primary outcomes:
measure: Number of Patients With Progression to Small Bowel Transplantation.
timeFrame: 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 outcomes:
measure: Number of Subjects With Reversal of Biochemical Cholestasis
timeFrame: 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
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: David F Mercer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alwayn IP, Gura K, Nose V, Zausche B, Javid P, Garza J, Verbesey J, Voss S, Ollero M, Andersson C, Bistrian B, Folkman J, Puder M. Omega-3 fatty acid supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver disease. Pediatr Res. 2005 Mar;57(3):445-52. doi: 10.1203/01.PDR.0000153672.43030.75. Epub 2005 Jan 19.
citation: Van Aerde JE, Duerksen DR, Gramlich L, Meddings JB, Chan G, Thomson AB, Clandinin MT. Intravenous fish oil emulsion attenuates total parenteral nutrition-induced cholestasis in newborn piglets. Pediatr Res. 1999 Feb;45(2):202-8. doi: 10.1203/00006450-199902000-00008.
citation: Gura KM, Parsons SK, Bechard LJ, Henderson T, Dorsey M, Phipatanakul W, Duggan C, Puder M, Lenders C. Use of a fish oil-based lipid emulsion to treat essential fatty acid deficiency in a soy allergic patient receiving parenteral nutrition. Clin Nutr. 2005 Oct;24(5):839-47. doi: 10.1016/j.clnu.2005.05.020.
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: Diamond IR, Sterescu A, Pencharz PB, Kim JH, Wales PW. Changing the paradigm: omegaven for the treatment of liver failure in pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr. 2009 Feb;48(2):209-15. doi: 10.1097/MPG.0b013e318182c8f6.
citation: Mercer DF, Hobson BD, Fischer RT, Talmon GA, Perry DA, Gerhardt BK, Grant WJ, Botha JF, Langnas AN, Quiros-Tejeira RE. Hepatic fibrosis persists and progresses despite biochemical improvement in children treated with intravenous fish oil emulsion. J Pediatr Gastroenterol Nutr. 2013 Apr;56(4):364-9. doi: 10.1097/MPG.0b013e31827e208c.