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

Low Dose Parenteral Fat for the Prevention of Parenteral Nutrition Associated Cholestasis in Neonates With Congenital/Acquired Gastrointestinal Disorders

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.

Study Overview

• Status: Terminated
• Conditions: Cholestasis
• Intervention / Treatment: Drug: Intralipid; Drug: Intralipid

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 Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 minute to 5 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low dose intravenous fat emulsion; Subjects in this arm will receive approximately 1 g/kg/d IV of intravenous soybean oil (Intralipid).	Drug: Intralipid; The subject will receive 1 g/kg/d of the standard intravenous fat emulsion while receiving Parenteral Nutrition until discharge from the hospital, death or 100 days of life, whichever comes first.; Other Names: soybean oil; Drug: Intralipid; The subject will receive 3 g/kg/d of the standard intravenous fat emulsion while receiving Parenteral Nutrition until discharge from the hospital, death or 100 days of life, whichever comes first.; Other Names: soybean oil
Active Comparator: standard dose intravenous fat emulsion; Subjects in this arm will receive approximately 3 g/kg/d IV of intravenous soybean oil (Intralipid).	Drug: Intralipid; The subject will receive 1 g/kg/d of the standard intravenous fat emulsion while receiving Parenteral Nutrition until discharge from the hospital, death or 100 days of life, whichever comes first.; Other Names: soybean oil; Drug: Intralipid; The subject will receive 3 g/kg/d of the standard intravenous fat emulsion while receiving Parenteral Nutrition until discharge from the hospital, death or 100 days of life, whichever comes first.; Other Names: soybean oil

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality Rate	death	at the end of the hospital stay which is expected to be an average of 5 weeks
Anthropometric Measurements	Growth will be assessed by growth velocity at 28 days of age	28 days of age
Anthropometric Measurements	Growth will be assessed by weight at the time of hospital discharge (approximately 5 weeks)	approximately 5 weeks

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: St. Louis University

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: June 6, 2011
• First Submitted That Met QC Criteria: June 14, 2011
• First Posted (Estimate): June 15, 2011

Study Record Updates

• Last Update Posted (Estimate): June 16, 2016
• Last Update Submitted That Met QC Criteria: May 10, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: neonates; parenteral nutrition; cholestasis; gastrointestinal disorders
• Additional Relevant MeSH Terms: Biliary Tract Diseases; Bile Duct Diseases; Gastrointestinal Diseases; Digestive System Diseases; Cholestasis; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Soybean oil, phospholipid emulsion
• Other Study ID Numbers: 10-001714

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO