Cholestasis Reversal: Efficacy of IV Fish Oil

NCT00910104 | Completed Phase 2 Results DMC

• 2 other identifiers: 05-04-0481R01FD003460-02
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether Omegaven is effective in the treatment of parenteral nutrition associated liver disease (PNALD).

Conditions

Parenteral Nutrition Associated Liver Disease; Short Bowel Syndrome; Gastrointestinal Disease

Keywords

PNALD; Omegaven; Parenteral Nutrition Associated Liver Disease; Cholestasis; Short Bowel Syndrome

Outcome Measures

Primary Outcomes (1)

• Reversal of Cholestasis, Defined as a Direct Bilirubin to <= 2.0 mg/dL.

  Time to reversal of established parenteral nutrition associated liver disease, defined as a decrease in direct bilirubin to \<= 2.0 mg/dL.

  Duration of treatment

Study Arms (1)

Omegaven

EXPERIMENTAL

1g/kg/day for duration of study participation for all participants

Drug: Omegaven®

Interventions

Omegaven® DRUG

10% Omegaven® 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated

Also known as: Fish Oil Lipid Emulsion (FOLE)

Omegaven

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients will be PN dependent (unable to meet nutritional needs solely by enteral nutrition) and are expected to require PN for at least another 30 days
• Patients considered eligible for study participation must have parenteral nutrition associated liver disease (PNALD) as defined as a direct bilirubin of \> 2 mg/dl or currently on Omegaven through another protocol. Other causes of liver disease should be excluded. A liver biopsy is not necessary for treatment.
• Direct bilirubin \> 2.0 mg/dl or already on Omegaven through another protocol
• Signed patient informed consent.
• The patient must have utilized standard therapies to prevent the progression of his/her liver disease including surgical treatment, cyclic PN, avoiding overfeeding, reduction/removal of copper and manganese from PN, advancement of enteral feeding, and the use of ursodiol (i..e., Actigall®).

You may not qualify if:

• Pregnancy
• Other causes of chronic liver disease (Hepatitis C, biliary atresia, and alpha 1 anti-trypsin deficiency).
• Enrollment 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
• In rare instances, patients diagnosed with PNALD may later be found to have liver disease due to other causes in addition to the use of PN (i.e., inborn errors of metabolism, viral infections ). Such causes may not be known at the time of enrollment and will not preclude them from continuing in the study. For the sake of statistical analysis, however, these patients will be excluded although all data will be collected and reviewed.

Sponsors & Collaborators

• Mark Puder: lead

Study Sites (1)

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Related Publications (11)

• 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.

  PMID: 18310188 BACKGROUND

• 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. doi: 10.1542/peds.2005-2662.

  PMID: 16818533 BACKGROUND

• Nandivada P, Anez-Bustillos L, O'Loughlin AA, Mitchell PD, Baker MA, Dao DT, Fell GL, Potemkin AK, Gura KM, Neufeld EJ, Puder M. Risk of post-procedural bleeding in children on intravenous fish oil. Am J Surg. 2017 Oct;214(4):733-737. doi: 10.1016/j.amjsurg.2016.10.026. Epub 2016 Dec 1.

  PMID: 27979360 BACKGROUND

• Nandivada P, Baker MA, Mitchell PD, O'Loughlin AA, Potemkin AK, Anez-Bustillos L, Carlson SJ, Dao DT, Fell GL, Gura KM, Puder M. Predictors of failure of fish-oil therapy for intestinal failure-associated liver disease in children. Am J Clin Nutr. 2016 Sep;104(3):663-70. doi: 10.3945/ajcn.116.137083. Epub 2016 Aug 10.

  PMID: 27510535 BACKGROUND

• Nandivada P, Fell GL, Mitchell PD, Potemkin AK, O'Loughlin AA, Gura KM, Puder M. Long-Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure-Associated Liver Disease [Formula: see text]. JPEN J Parenter Enteral Nutr. 2017 Aug;41(6):930-937. doi: 10.1177/0148607116633796. Epub 2016 Mar 9.

  PMID: 26962059 BACKGROUND

• Nandivada P, Chang MI, Potemkin AK, Carlson SJ, Cowan E, O'loughlin AA, Mitchell PD, Gura KM, Puder M. The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy. Ann Surg. 2015 Jan;261(1):172-9. doi: 10.1097/SLA.0000000000000445.

  PMID: 24374535 BACKGROUND

• Le HD, de Meijer VE, Robinson EM, Zurakowski D, Potemkin AK, Arsenault DA, Fallon EM, Malkan A, Bistrian BR, Gura KM, Puder M. Parenteral fish-oil-based lipid emulsion improves fatty acid profiles and lipids in parenteral nutrition-dependent children. Am J Clin Nutr. 2011 Sep;94(3):749-58. doi: 10.3945/ajcn.110.008557. Epub 2011 Jul 20.

  PMID: 21775562 BACKGROUND

• 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.

  PMID: 19661785 RESULT

• Gura KM, Calkins KL, Premkumar MH, Puder M. Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events. J Pediatr. 2022 Feb;241:173-180.e1. doi: 10.1016/j.jpeds.2021.10.030. Epub 2021 Oct 23.

  PMID: 34695449 DERIVED

• Gura KM, Premkumar MH, Calkins KL, Puder M. Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study. J Pediatr. 2021 Mar;230:46-54.e2. doi: 10.1016/j.jpeds.2020.09.068. Epub 2020 Oct 8.

  PMID: 33038344 DERIVED

• Gura K, Premkumar MH, Calkins KL, Puder M. Intravenous Fish Oil Monotherapy as a Source of Calories and Fatty Acids Promotes Age-Appropriate Growth in Pediatric Patients with Intestinal Failure-Associated Liver Disease. J Pediatr. 2020 Apr;219:98-105.e4. doi: 10.1016/j.jpeds.2019.12.065. Epub 2020 Feb 12.

  PMID: 32059815 DERIVED

MeSH Terms

Conditions

Short Bowel Syndrome; Gastrointestinal Diseases; Cholestasis

Interventions

fish oil triglycerides

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Digestive System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bile Duct Diseases; Biliary Tract Diseases

Results Point of Contact

• Title: Mark Puder MD PhD
• Organization: Boston Children's Hospital

mark.puder@childrens.harvard.edu

617-355-1838

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D., Ph.D

Study Record Dates

• First Submitted: May 20, 2009
• First Posted: May 29, 2009
• Study Start: August 1, 2006
• Primary Completion: January 23, 2019
• Study Completion: January 23, 2019
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Locations

US (1)