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

NCT ID: NCT01373918

Last Updated: 2016-06-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2014-07-31

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.

Conditions

Cholestasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

low dose intravenous fat emulsion

Subjects in this arm will receive approximately 1 g/kg/d IV of intravenous soybean oil (Intralipid).

Group Type: EXPERIMENTAL

Intralipid

Intervention Type: DRUG

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.

standard dose intravenous fat emulsion

Subjects in this arm will receive approximately 3 g/kg/d IV of intravenous soybean oil (Intralipid).

Group Type: ACTIVE_COMPARATOR

Intralipid

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

soybean oil; soybean oil

Eligibility 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)

• Minimum Eligible Age: 1 Minute
• Maximum Eligible Age: 5 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Louis University

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Kara L. Calkins, MD

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kara L Calkins, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

University of California, Los Angeles

Los Angeles, California, United States

Saint Louis University

St Louis, Missouri, United States

Countries

United States

Other Identifiers

10-001714

Identifier Type: -

Identifier Source: org_study_id