Omegaven® in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury

Total Parenteral Nutrition-induced Cholestasis Clinical Trial

Official title:

Use of a Fish Oil-Based Intravenous Lipid Emulsion (Omegaven®) in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01845116
• Other study ID #: Omegaven 04-10-18B
• Status: Completed
• Phase: Phase 2
• Start date: July 2010
• Est. completion date: July 2020

Study information

• Verified date: September 2022
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the omega-3 fatty acid emulsion (Omegaven®), when used in place of the conventional soy-based fat emulsion (Intralipid), is effective in treating parenteral nutrition associated liver disease (PNALD) in children.

The study hypothesis is that Omegaven® can be safely provided to children who are dependent on parenteral nutrition and have PNALD, and can reverse or prevent progression of PNALD until the child can take adequate nutrition by mouth.

Description:

Rationale for Omegaven® Treatment

Unlike conventional intravenous fat emulsions, Omegaven® is comprised solely of fish oils containing primarily omega-3 fatty acids. Animal studies have shown that IV lipid emulsions such as fish oil that are high in eicosapentaenic and docosahexaenoic acid reduce impairment of bile flow as seen in cholestasis caused by conventional fat emulsions(1,2). By administering Omegaven® in place of conventional phytosterol/soybean fat emulsions, the cholestasis may be reversed and patients will be able to be maintained on adequate PN until they are able to ingest adequate nutrition enterally.

References

1. Chen W. Effects of fat emulsions with different fatty acid composition on plasma and hepatic lipids in rats receiving total parenteral nutrition. Clinical Nutrition 1996;15:24.

2. Yeh S. Effects of fish oil and safflower oil emulsions on diet-induced hepatic steatosis in rats receiving total parenteral nutrition. Clinical Nutrition 1996;15:80.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: July 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Weeks to 18 Years

Eligibility

Inclusion Criteria:

• Children 0-18 years of age

• Patients will be PN-dependent and expected to continue PN for at least 30 days

• Patients considered eligible for study participation must have PN-associated liver diseases . Other causes of liver disease (i.e., biliary atresia, galactosemia, alpha-1 antitrypsin deficiency) will be excluded. A liver biopsy is not necessary for treatment

• Direct bilirubin > 2.0 mg/dl

• Signed patient informed consent

• Signed patient assent where applicable.

Exclusion Criteria:

• Pregnancy

• Other causes of chronic liver disease (cystic fibrosis, biliary atresia, alpha-1 antitrypsin deficiency)

• Signs of advanced liver disease including cirrhosis on biopsy, varices, ascites

• The patient is allergic to eggs/shellfish

• The patient has a severe hemorrhagic disorder

• The patient is enrolled in any other clinical trial involving an investigational agent (unless approved by the designated physicians on the multidisciplinary team)

• The parent or guardian or child unwilling to provide consent or assent.

Related Conditions & MeSH terms

• Cholestasis
• Total Parenteral Nutrition-induced Cholestasis

Intervention

Drug:
• Omegaven®
10% Omegaven® initiated at a starting dose of 0.5g/kg/day for two days and then advancing to the goal dose of 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated.

Locations

Country	Name	City	State
United States	Levine Children's Hospital at Carolinas HealthCare System	Charlotte	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

References & Publications (3)

Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR, Puder M. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics. 2006 Jul;118(1):e197-201. — View Citation

Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP, Arsenault DA, Strijbosch RA, Lopes S, Duggan C, Puder M. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008 Mar;121(3):e678-86. doi: 10.1542/peds.2007-2248. — View Citation

Puder M, Valim C, Meisel JA, Le HD, de Meijer VE, Robinson EM, Zhou J, Duggan C, Gura KM. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg. 2009 Sep;250(3):395-402. doi: 10.1097/SLA.0b013e3181b36657. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Normalization of Direct Bilirubin	Normalization of direct bilirubin is defined as less than 0.4mg/dL by 9 months.; This relates to the efficacy of parenteral administration of fish oil derived fat emulsion (Omegaven®) to reverse established parenteral nutrition associated liver disease.	Month 9
Secondary	Number of Participants With Normal Essential Fatty Acid (EFA) Profiles.	EFA is defined at a triene tetraene ratio of greater than 0.2 (so normal is > 0.2). Collected monthly from month 1-9.	Months 1 through 9
Secondary	Number of Participants With Triglyceride Levels > 400 mg/dL	Number of participants with triglyceride levels > 400 mg/dL	baseline data and then weekly and monthly evaluations, for an average of 9 months
Secondary	Number of Participants With Unexpected Bleeding or Coagulopathies		Month 6