Clinical trial NCT00969332: A Safety and Efficacy Study to Determine if Giving Intravenous Fish Oil Helps Children With Liver Disease
Official title: Omegaven and Parenteral Nutrition Associated Cholestasis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cholestasis
Keywords: liver
parenteral nutrition
fish oil
omegaven
children
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2009-09-01
Enrollment: 62
Sex: ALL
Minimum age (years): 2
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 the study is to investigate if intravenous fish oil, commercially available as Omegaven, safely and effectively reverses parenteral nutrition associated cholestasis in children.

Detailed description: Infants dependent on parenteral nutrition for greater than 1 year who develop parenteral nutrition associated cholestasis will universally face mortality unless they receive a timely liver and/or small bowel transplant. Although transplant survival has improved in recent years, survival is not guaranteed, and transplant care remains costly. Alternative nutritional and pharmacological strategies are imperative to improve the clinical outcomes of infants with intestinal failure and parenteral nutrition associated cholestasis. In both animal and human studies, intravenous fish oil, a lipid emulsion rich in omega-3 fatty acids and Vitamin E, and lacking phytosterols, has been shown to ameliorate parenteral nutrition associated cholestasis and improve morbidity and mortality. The purpose of this pilot study is to investigate if Omegaven, a commercially available intravenous fish oil, at 1 g/kg/d, will safely reverse liver disease in 80 subjects with parenteral nutrition associated cholestasis. Subjects can initially receive a maximum of 6 months (24 weeks) of intravenous fish oil. If the subject re-develops liver disease and still satisfies inclusion/exclusion criteria, the intervention can be restarted. Study subjects will be compared to a historical cohort of children with Short Bowel Syndrome and parenteral nutrition associated cholestasis who have been receiving standard intravenous soybean oil for \> 60 days. The fish oil cohort will be followed for a total of 5 years to determine if transplant-free mortality is reduced.

Eligibility criteria: Inclusion Criteria:

* Clinical evidence of parenteral nutrition associated cholestasis
* Direct bilirubin greater or equal to 2 mg/dL on 2 consecutive measurements
* Expected parenteral nutrition course greater than 30 days
* Acquired or congenital gastrointestinal disease
* \> 2 weeks of age and \< 18 years of age
* \> 60% calories from parenteral nutrition
* Failed standard therapies to prevent progression of liver disease (Actigal, cyclic parenteral nutrition, avoidance of overfeeding, reduction/removal of copper from parenteral nutrition if elevated my laboratory analysis, advancement of enteral feeds)

Exclusion Criteria:

* Inborn errors of metabolism
* Extracorporeal Membrane Oxygenation
* Seafood, egg, or Omegaven allergy
* Documented case of liver disease other than Parenteral Nutrition Associated Cholestasis
* Hemorrhagic disorder
* Anticoagulant therapy
* Hemodynamically unstable or in shock
* Comatose state
* Stroke, pulmonary embolism, recent myocardial infarction
* Diabetes
* Fatal chromosomal disorder
* Enrollment in any other clinical trial involving an investigational agent
* Patient, parent, or legal guardians unable or unwilling to give consent
* Patient expected to be weaned from parenteral nutrition in 30 days
* unable to tolerate necessary monitoring
* Patient requiring aspirin or toradel or motrin
* Patient requiring dialysis

Primary outcomes:
measure: Time to Reversal of Parenteral Nutrition Associated Cholestasis
timeFrame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Secondary outcomes:
measure: Death
timeFrame: 24 weeks, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
measure: Number of Participants Who Underwent a Transplant
timeFrame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
measure: Time to Full Enteral Feeds
timeFrame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
measure: Growth Z-scores
timeFrame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
measure: Platelet Counts at the End of the Study - Risk of Bleeding
timeFrame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
measure: Number of Participants With Essential Fatty Acid Deficiency
timeFrame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
measure: Markers of Inflammation
timeFrame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
measure: Markers of Sterol Metabolism
timeFrame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
measure: Markers of Bile Acid Metabolism
timeFrame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
measure: Markers of Fatty Acid Metabolism
timeFrame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Kara L Calkins, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Calkins KL, Dunn JC, Shew SB, Reyen L, Farmer DG, Devaskar SU, Venick RS. Pediatric intestinal failure-associated liver disease is reversed with 6 months of intravenous fish oil. JPEN J Parenter Enteral Nutr. 2014 Aug;38(6):682-92. doi: 10.1177/0148607113495416. Epub 2013 Jul 26.
citation: Calkins KL, DeBarber A, Steiner RD, Flores MJ, Grogan TR, Henning SM, Reyen L, Venick RS. Intravenous Fish Oil and Pediatric Intestinal Failure-Associated Liver Disease: Changes in Plasma Phytosterols, Cytokines, and Bile Acids and Erythrocyte Fatty Acids. JPEN J Parenter Enteral Nutr. 2018 Mar;42(3):633-641. doi: 10.1177/0148607117709196. Epub 2017 Dec 18.
citation: Wang C, Venick RS, Shew SB, Dunn JCY, Reyen L, Gou R, Calkins KL. Long-Term Outcomes in Children With Intestinal Failure-Associated Liver Disease Treated With 6 Months of Intravenous Fish Oil Followed by Resumption of Intravenous Soybean Oil. JPEN J Parenter Enteral Nutr. 2019 Aug;43(6):708-716. doi: 10.1002/jpen.1463. Epub 2018 Nov 8.
citation: Ong ML, Venick RS, Shew SB, Dunn JCY, Reyen L, Grogan T, Calkins KL. Intravenous Fish Oil and Serum Fatty Acid Profiles in Pediatric Patients With Intestinal Failure-Associated Liver Disease. JPEN J Parenter Enteral Nutr. 2019 Aug;43(6):717-725. doi: 10.1002/jpen.1532. Epub 2019 Mar 22.
citation: Calkins KL, Thamotharan S, Ghosh S, Dai Y, Devaskar SU. MicroRNA 122 Reflects Liver Injury in Children with Intestinal Failure-Associated Liver Disease Treated with Intravenous Fish Oil. J Nutr. 2020 May 1;150(5):1144-1150. doi: 10.1093/jn/nxaa001.