Low Dose Fat for the Prevention of Liver Disease in Babies With Gastrointestinal Disorders

Phase 4

Terminated

• Conditions: Cholestasis
• Interventions: Drug: Intralipid

• Registration Number: NCT01373918
• Lead Sponsor: University of California, Los Angeles

Brief Summary

Neonates with congenital/acquired gastrointestinal disorders are at high risk for Parenteral Nutrition Associated Cholestasis (PNAC). Besides enteral nutrition, standard therapies to prevent and treat PNAC have been limited and marginal. Recently, the dose and composition of standard intravenous fat emulsions have implicated in the development and progression of PNAC.

In this study, neonates with congenital/acquired gastrointestinal disorders will be randomized, in a unblinded fashion, to receive either the standard dose of an intravenous omega-6 fatty acid emulsion or a low dose of an intravenous omega-6 fatty acid emulsion throughout their course of PN or until hospital discharge, death or 100 days of life, whichever comes first. The primary outcome will be the presence of cholestasis.

Detailed Description

Parenteral Nutrition (PN) acts as an intravenous source of both macronutrients and micronutrients when enteral feeds are not possible. Intravenous fat emulsions often supplement PN and provide a dense source of non-protein calories and essential fatty acids. Although PN is life-sustaining, it is associated with a myriad of life-threatening complications including Parenteral Nutrition Associated Cholestasis (PNAC). Children dependent on PN for an extended period of time are high risk for liver failure.

The etiology of PNAC remains poorly understood. Neonates with congenital and acquired gastrointestinal disorders are at high risk for PNAC and its subsequent complications. Examples of these gastrointestinal disorders include gastroschisis, volvulus, atresias, dysmotility and malabsorption disorders, pseudo-obstruction, and Hirschsprung's disease. These disorders often render the gut non-functional for extended periods of time. As a result, these patients become PN-dependent and develop PNAC.

Specific PN components have been implicated in the pathogenesis of PNAC. More recently, standard intravenous fat emulsions have been labeled as one of the main culprits contributing to PNAC. Standard intravenous fat emulsions are dosed as high as 4 g/kg/d and are derived from soybean and/or safflower oil, which are rich in omega-6 fatty acids and phytosterols and contain a paucity of omega-3 fatty acids. It is unclear if the dose or high omega-6 fatty acid:omega-3 fatty acid ratio and phytosterols is responsible for the development of PNAC.

The primary specific aim of this study is to determine if PNAC is related to the amount of standard intravenous fat emulsion administered to neonates with congenital/acquired gastrointestinal disorders. The investigators hypothesize that the PNAC is unrelated to the dose of intravenous fat emulsions. To test this hypothesis, neonates with congenital/acquired gastrointestinal disorders will be randomized to low dose standard soybean based parenteral fat, 1 g/kg/d, or standard dose soybean parenteral fat, 3 g/kg/d. Secondary outcomes include: mortality rate, length of stay, and anthropometric measurements at 28 days of life and at the end of the hospital stay, which is expected to be an average of 5 weeks.

Study Timeline

• Study Start: 2010-12
• Study First Submitted: 2011-06-06
• Study First Submitted QC: 2011-06-14
• Study First Posted: 2011-06-15
• Primary Completion: 2014-07
• Study Completion: 2014-07
• Results First Submitted: 2016-02-22
• Status Verified: 2016-05
• Results First Submitted QC: 2016-05-10
• Last Update Submitted: 2016-05-10
• Results First Posted: 2016-06-16
• Last Update Posted: 2016-06-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

• congenital or acquired gastrointestinal disorder
• age less than 5 days of life

Exclusion Criteria

• congenital intrauterine infection know to be associated with liver involvement
• known structural liver abnormalities
• known genetic disorders (trisomy 21, 13, and 18)
• inborn errors of metabolism
• infants meeting the criteria for terminal illness (ph:6.8>2 hours)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
standard dose intravenous fat emulsion	Intralipid	Subjects in this arm will receive approximately 3 g/kg/d IV of intravenous soybean oil (Intralipid).
low dose intravenous fat emulsion	Intralipid	Subjects in this arm will receive approximately 1 g/kg/d IV of intravenous soybean oil (Intralipid).

Primary Outcome Measures

Name	Time	Method
Presence of Cholestasis	prior to 100 days of life, hospital discharge, or death whichever comes first	Cholestasis will be defined by a direct bilirubin \> 2 mg/dL

Secondary Outcome Measures

Name	Time	Method
Mortality Rate	at the end of the hospital stay which is expected to be an average of 5 weeks	death
Anthropometric Measurements	approximately 5 weeks	Growth will be assessed by weight at the time of hospital discharge (approximately 5 weeks)

Trial Locations

Locations (2)

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Saint Louis University; 🇺🇸 Saint Louis, Missouri, United States