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

• ClinicalTrials.gov Identifier: NCT00969332
• Recruitment Status: Recruiting
• First Posted: September 1, 2009
• Last Update Posted: March 6, 2018
• Sponsor: University of California, Los Angeles
• Information provided by (Responsible Party): Kara L. Calkins, MD, University of California, Los Angeles

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cholestasis	Drug: Omegaven	Phase 2

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 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 up to two times for an additional 6 months (24 weeks) each time. 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Omegaven and Parenteral Nutrition Associated Cholestasis
• Study Start Date: August 2009
• Estimated Primary Completion Date: August 2019
• Estimated Study Completion Date: August 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Omegaven; 0.5 gm/kg/d intravenous every day for 2 days, then 1 gm/kg/d intravenous everyday

Outcome Measures

Primary Outcome Measures :

1. Time to reversal of Parenteral Nutrition Associated Cholestasis [ Time Frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first) ]
   serial liver function tests

Secondary Outcome Measures :

1. death [ Time Frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first) ]
   expiration
2. transplant [ Time Frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first) ]
   includes isolated liver or multi-visceral transplant including liver graft
3. time to full enteral feeds [ Time Frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first) ]
   discontinuation of parenteral nutrition
4. growth [ Time Frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first) ]
   Z-scores
5. risk for bleeding [ Time Frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first) ]
   serial platelet counts and international ratios
6. essential fatty acid deficiency [ Time Frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first) ]
   triene:tetrane ratio >0.2
7. markers of inflammation, liver injury, and sterol, lipid and bile acid metabolism [ Time Frame: during intervention and post-intervention ]
   serum cytokines, phytosterols, and bile acids, erythrocyte fatty acid profiles, and microRNA profiles
8. gut microbiome [ Time Frame: during intervention and post-intervention ]
   intestinal microbiome

Eligibility Criteria

• Ages Eligible for Study: up to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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
• 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 weaned from parenteral nutrition in 30 days
• unable to tolerate necessary monitoring

Contacts and Locations

Locations

United States, California

University of California, Los Angeles; Recruiting

Los Angeles, California, United States, 90095

Contact: Kara L Calkins, MD 310-794-9855 KCalkins@mednet.ucla.edu

Contact: Robert Venick, MD (310) 206-6134 RVenick@mednet.ucla.edu

Principal Investigator: Kara L Calkins, MD

Sub-Investigator: Stephen B Shew, MD

Sub-Investigator: James Dunn, MD, PhD

Sub-Investigator: Robert Venick, MD

Sponsors and Collaborators

University of California, Los Angeles

Investigators

• Principal Investigator: Kara L Calkins, MD; University of California, Los Angeles

More Information

• Responsible Party: Kara L. Calkins, MD, Assistant Professor, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT00969332
• Other Study ID Numbers: 09-02-079-02
• First Posted: September 1, 2009
• Last Update Posted: March 6, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Kara L. Calkins, MD, University of California, Los Angeles:

liver; Parenteral Nutrition; fish oil; Omegaven; children

Additional relevant MeSH terms:

Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases