A Safety and Efficacy Study to Determine if Giving Intravenous Fish Oil Helps Children With Liver Disease

Phase 2

Terminated

Conditions: Cholestasis

Interventions: Drug: Omegaven

Registration Number: NCT00969332

Lead Sponsor: University of California, Los Angeles

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 62

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Omegaven	Omegaven	0.5 g/kg/d IV x 2 days, then 1 g/kg/d IV for 24 weeks or until parenteral nutrition discontinuation, death or transplant, whichever comes first. Subjects are eligible to restart Omegaven should they re-satisfy inclusion/exclusion criteria.

Primary Outcome Measures

Name	Time	Method
Time to Reversal of Parenteral Nutrition Associated Cholestasis	24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)	weeks

Secondary Outcome Measures

Name	Time	Method
Time to Full Enteral Feeds	24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)	discontinuation of parenteral nutrition
Death	24 weeks, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)	expiration
Number of Participants Who Underwent a Transplant	24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)	includes isolated liver or multi-visceral transplant including liver graft
Growth Z-scores	24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)	Weight Z-scores at the end of the study. Formula used: (weight at end of study-average weight of reference population)/standard deviation of weight of reference population. The Z-score indicates the number of standard deviations away from the mean. A weight Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A weight Z-score \</= -2 indicates an underweight or malnourished status, while a weight Z-score \>/= 2 indicates an overweight or obese status.
Platelet Counts at the End of the Study - Risk of Bleeding	24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)	platelet counts at the end of the study
Markers of Inflammation	24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)	Serum Cytokines - interleukin-8
Markers of Bile Acid Metabolism	24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)	Serum Bile acids - total chenodeoxycholic acid
Number of Participants With Essential Fatty Acid Deficiency	24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)	triene:tetraene ratio less than 0.2
Markers of Sterol Metabolism	24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)	Serum Phytosterols - stigmasterol
Markers of Fatty Acid Metabolism	24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)	Erythrocyte fatty acid - Docosahexaenoic Acid