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

Cholestasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01373918
• Other study ID #: 10-001714
• Status: Completed
• Phase: Phase 4
• First received: June 6, 2011
• Last updated: December 1, 2014
• Start date: December 2010
• Est. completion date: July 2014

Study information

• Verified date: December 2014
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 mg/kg/d and are derived from soybean and/or safflower oil, which are rich in omega-6 fatty acids 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 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 gm/kg/d, or standard dose soybean parenteral fat, 3 gm/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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 5 Days

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cholestasis
• Digestive System Diseases
• Gastrointestinal Diseases

Intervention

Drug:
• Intralipid
The subject will receive 1 gm/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.
• Intralipid
The subject will receive 3 gm/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.

Locations

Country	Name	City	State
United States	University of California, Los Angeles	Los Angeles	California
United States	Saint Louis University	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	St. Louis University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	mortality rate	death	at the end of the hospital stay which is expected to be an average of 5 weeks	Yes
Secondary	anthropometric measurements	Growth will be assessed by growth velocity at 28 days days of life and at end of the hospital stay	28 days and at the end of the hospital stay which is expected to be an average of 5 weeks	Yes