Efficacy and Safety of Omega-3 Lipid Therapy in Pediatric Patients With Parenteral Nutrition-Associated Liver Disease

Study Overview
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Brief Summary
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This pilot study seeks to demonstrate the efficacy of an intravenous lipid preparation high in omega-3 fatty acids (Omegaven) in the treatment of cholestasis in parenteral nutrition dependent patients with short gut syndrome.

Official Title
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Efficacy and Safety of Omega-3 Lipid Therapy in Pediatric Patients With Parenteral Nutrition-Associated Liver Disease

Conditions
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Short Bowel Syndrome, Cholestasis

Intervention / Treatment
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* Drug: Omegaven Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient will be dependent upon parenteral nutrition (PN) Patient will have short gut syndrome (loss of >50% of small bowel) Patient's guardian/caregiver provides informed consent for patient to receive therapy Pediatric patient ≤ 1 year of age Expected PN duration is greater than 30 days Direct bilirubin >2.0 mg/dL measured on two occasions no more than one week apart Exclusion Criteria: Liver dysfunction secondary to cause other than PN verified by standard of care diagnostic procedures and lab work to rule out alternative causes of neonatal cholestasis. Any patient in whom Omegaven therapy would be contraindicated, such as an allergy to any seafood product, egg protein, and/or previously established allergy to Omegaven impaired lipid metabolism severe hemorrhagic disorder unstable diabetes mellitus collapse and shock, stroke/embolism, recent cardiac infarction, or undefined coma status

Ages Eligible for Study
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Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omegaven Therapy<br>After baseline labs, which have been collected no earlier than seven days prior to the initiation of therapy are obtained, therapy with Omegaven will be initiated at a starting dose of 0.5 g/kg/day infused over 12 hours. If tolerated, the dose will be increased to 1 g/kg/day, the goal dose. Omegaven will be infused intravenously through either a central or peripheral catheter in conjunction with parenteral nutrition. | Drug: Omegaven Therapy<br>* After baseline labs, which have been collected no earlier than seven days prior to the initiation of therapy are obtained, therapy with Omegaven will be initiated at a starting dose of 0.5 g/kg/day infused over 12 hours. If tolerated, the dose will be increased to 1 g/kg/day, the goal dose. Omegaven will be infused intravenously through either a central or peripheral catheter in conjunction with parenteral nutrition.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of liver dysfunction as measured by time to achieve 50 % decrease in direct bilirubin | Direct bilirubin will be collected at baseline, then weekly for 30 days, and then biweekly, thereafter, up to an expected average of 108 weeks | weekly then biweekly data collection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| a) Maintenance of nutritional status | Nutritional status will be monitored by reviewing complete metabolic panel, magnesium, weight, vitals, phosphorus, prealbumin, lipid panel, and essential free fatty acid profile. The essential fatty acid profile will be checked at baseline and then monthly for at least 6 months until the patient is determined to be receiving at least 2.7% of caloric intake from linoleic acid. If the patient's essential fatty acid profile indicates that the patient is absorbing adequate amounts of essential fatty acid, the essential fatty acid profile will be discontinued . | Labwork will be collected at baseline, then weekly for the first month. Thereafter, a lipid panel will be collected every 2 months, complete metabolic panel every 2 weeks, and essential fatty acid profile monthly, up to an expected average of 108 weeks | 
| Occurrence of potential adverse side effects | Adverse events may include but are not limited to prolonged prothrombin time, hypertriglyceridemia, and anaphylaxis in relation to the patient's therapy. | biweekly labwork up to an expected average of 108 weeks | 
| c) Resolution of liver dysfunction | Resolution of liver dysfunction will be defined by achievement of normal direct bilirubin, aspartate aminotransferase and alanine transaminase. | weekly complete metabolic panel for the first month and then biweekly thereafter, up to an expected average of 108 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Short bowel syndrome, Cholestasis, Omegaven, Parenteral nutrition-associated Liver Disease