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

This study has been completed.
Sponsor:
Collaborator:
St. Louis University
Information provided by (Responsible Party):
Kara L. Calkins, MD, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01373918
First received: June 6, 2011
Last updated: December 1, 2014
Last verified: December 2014
  Purpose

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 Intervention Phase
Cholestasis
Drug: Intralipid
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • presence of cholestasis [ Time Frame: prior to 100 days of life, hospital discharge, or death whichever comes first ] [ Designated as safety issue: Yes ]
    Cholestasis will be defined by a direct bilirubin > 2 mg/dL


Secondary Outcome Measures:
  • mortality rate [ Time Frame: at the end of the hospital stay which is expected to be an average of 5 weeks ] [ Designated as safety issue: Yes ]
    death

  • anthropometric measurements [ Time Frame: 28 days and at the end of the hospital stay which is expected to be an average of 5 weeks ] [ Designated as safety issue: Yes ]
    Growth will be assessed by growth velocity at 28 days days of life and at end of the hospital stay


Enrollment: 42
Study Start Date: December 2010
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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.
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 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.
Other Name: soybean oil

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 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.

  Eligibility

Ages Eligible for Study:   up to 5 Days
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01373918

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

No publications provided

Responsible Party: Kara L. Calkins, MD, Clinical Assistant Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01373918     History of Changes
Other Study ID Numbers: 10-001714
Study First Received: June 6, 2011
Last Updated: December 1, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:
cholestasis
neonates
parenteral nutrition
gastrointestinal disorders

Additional relevant MeSH terms:
Cholestasis
Digestive System Diseases
Gastrointestinal Diseases
Bile Duct Diseases
Biliary Tract Diseases
Fat Emulsions, Intravenous
Parenteral Nutrition Solutions
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015