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

Phase 2TerminatedNCT00969332

University of California, Los Angeles62 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cholestasis

Interventions

OmegavenDRUG

0.5 g/kg/d intravenous every day for 2 days, then 1 g/kg/d intravenous everyday

Eligibility

Sex: ALLMin age: 2 WeeksMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

University of California, Los Angeles

Los Angeles, California, United States

Outcomes

Primary Outcomes

Time to Reversal of Parenteral Nutrition Associated Cholestasis

weeks

Time frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)

Secondary Outcomes

Death

expiration

Time frame: 24 weeks, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)

Number of Participants Who Underwent a Transplant

includes isolated liver or multi-visceral transplant including liver graft

Time frame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)

Time to Full Enteral Feeds

discontinuation of parenteral nutrition

Time frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)

Growth Z-scores

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.

Time frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)

Platelet Counts at the End of the Study - Risk of Bleeding

platelet counts at the end of the study

Time frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)

Data from ClinicalTrials.gov

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