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

• ClinicalTrials.gov Identifier: NCT01373918
• Recruitment Status: Terminated
• First Posted: June 15, 2011
• Results First Posted: June 16, 2016
• Last Update Posted: June 16, 2016
• Sponsor: University of California, Los Angeles
• Collaborator: St. Louis University
• Information provided by (Responsible Party): Kara L. Calkins, MD, University of California, Los Angeles

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cholestasis	Drug: Intralipid	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Low Dose Parenteral Fat for the Prevention of Parenteral Nutrition Associated Cholestasis in Neonates With Congenital/Acquired Gastrointestinal Disorders
• Study Start Date: December 2010
• Actual Primary Completion Date: July 2014
• Actual Study Completion Date: July 2014

Arms and Interventions

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 Name: 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 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 Name: soybean oil

Outcome Measures

Primary Outcome Measures :

1. Presence of Cholestasis [ Time Frame: 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 :

1. Mortality Rate [ Time Frame: at the end of the hospital stay which is expected to be an average of 5 weeks ]
   death
2. Anthropometric Measurements [ Time Frame: 28 days of age ]
   Growth will be assessed by growth velocity at 28 days of age
3. Anthropometric Measurements [ Time Frame: approximately 5 weeks ]
   Growth will be assessed by weight at the time of hospital discharge (approximately 5 weeks)

Eligibility Criteria

• Ages Eligible for Study: up to 5 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, California

University of California, Los Angeles

Los Angeles, California, United States, 90095

United States, Missouri

Saint Louis University

Saint Louis, Missouri, United States, 63104

Sponsors and Collaborators

University of California, Los Angeles

St. Louis University

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: NCT01373918 History of Changes
• Other Study ID Numbers: 10-001714
• First Posted: June 15, 2011
• Results First Posted: June 16, 2016
• Last Update Posted: June 16, 2016
• Last Verified: May 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

cholestasis; neonates; parenteral nutrition; gastrointestinal disorders

Additional relevant MeSH terms:

Cholestasis; Gastrointestinal Diseases; Digestive System Diseases; Bile Duct Diseases; Biliary Tract Diseases; Soybean oil, phospholipid emulsion; Fat Emulsions, Intravenous; Parenteral Nutrition Solutions; Pharmaceutical Solutions