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SMOFlipid to Lessen the Severity of Neonatal Cholestasis

Primary Purpose

Cholestasis, Jaundice, Obstructive

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SMOFlipid
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Cholestasis focused on measuring Parenteral nutrition, Total, Infant, newborn, Cholestasis, Enterocolitis, Necrotizing

Eligibility Criteria

23 Weeks - 1 Year (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Greater than 14 days old and less than 1 year of age.
  • Greater than 1 kg.
  • Mild cholestasis, defined as a conjugated bilirubin between 0.5-1.9 mg/dL
  • Currently standard therapy with soy-based Intralipid
  • Evidence of growth of weight, head circumference or length below our standards for post-menstrual age for at least 1 week.
  • Be expected to require intravenous nutrition for at least an additional 21 days

Exclusion Criteria:

  • Have a congenitally lethal condition.
  • Have clinically severe bleeding or clinical liver failure not able to be managed with routine measures.
  • Have evidence of a viral hepatitis or primary liver disease as the primary etiology of their cholestasis.
  • Have other health problems such that survival is extremely unlikely even if the infant's cholestasis improves

Sites / Locations

  • University of Florida

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SMOFlipid

Arm Description

Subjects with cholestasis will receive 3 G/kg/day of intravenous SMOFlipid daily until parenteral nutrition (PN) is discontinued. In addition, the following monitoring for effects of SMOFlipid will be performed: total days of parenteral nutrition, maximum conjugated bilirubin, time to resolution of bilirubin, time to liver transplant, time to death, positive blood cultures, rates of increase in weight, length, and head circumference, time dependent changes in liver function tests, including triglycerides, and length of hospital stay.

Outcomes

Primary Outcome Measures

Inflammation of the Liver Between the Groups
Inflammation of the liver will be evaluated by comparing direct bilirubin values between the two groups.

Secondary Outcome Measures

Measurement of Head Circumference for Growth Increase
Growth increase will be measured by head circumference of participants.
Measurement of Weight for Growth Increase
Growth increase will be measured by weight of participants.
Measurement of Length for Growth Increase
Growth increase will be measured by length of participants.
Number of Subjects Requiring Surgery
Number of Concomitant Medications Received
Length of IV Nutritional Therapy
Number of Subjects Receiving Formula Diet
Enteral administration of formula will be noted
Number of Subjects Receiving Breast Milk Diet
Enteral administration of breast milk will be noted
Number of Participants With Adverse Events Related to Treatment
Laboratory values will be used to determine adverse events.
Carbon Dioxide Total
Laboratory value that determines acid-base balance
Total Protein
Laboratory value that evaluates liver function
Albumin
Laboratory value that evaluates liver function
Aspartate Aminotransferase
Laboratory value that evaluates liver function
Alanine Aminotransferase
Laboratory value that evaluates liver function
Total Bilirubin
Laboratory value that evaluates liver function
Serum Glucose
Laboratory values that evaluates glucose in the blood
Alkaline Phosphatase
Laboratory value that evaluates liver function
Triglyceride
Laboratory value that evaluates liver function and metabolism of fat

Full Information

First Posted
February 23, 2016
Last Updated
March 3, 2017
Sponsor
University of Florida
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1. Study Identification

Unique Protocol Identification Number
NCT02721277
Brief Title
SMOFlipid to Lessen the Severity of Neonatal Cholestasis
Official Title
Compassionate Use of an Intravenous Fat Emulsion Comprised of Soy Oil, Medium Chain Triglycerides, Olive Oil, and Fish Oil for Neonates With Parenteral Nutrition Induced Liver Injury
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Study Start Date
May 2016 (Actual)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
February 2, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Parenteral nutrition (PN) provides intravenous nutritional supplementation for infants unable to absorb adequate enteral nutrients secondary to insufficient intestinal length or function. In early PN-associated cholestasis, the dose of traditional soy based lipid is limited to 1 g/kg/day which often limits the growth capacity of parenteral nutrition-dependent infants. Inadequate growth is directly related to poor neurological outcomes, failure to facilitate mechanical ventilation, and less growth of the neonate's already damaged intestine. Ultimately, these outcomes can lead to severe disability and death. To mitigate these deleterious effects and optimize growth, parenteral nutrition-dependent infants with cholestasis who are not adequately growing on 1 g/kg/day of soy-based lipid emulsion must have a greater intake of lipids to meet their needs for weight, length, and head circumference growth. SMOFlipid contains a mixture of 4 different lipid sources: soybean oil which provides essential fatty acids, olive oil which is high in monounsaturated fatty acids that are less susceptible to lipid peroxidation than polyunsaturated fatty acids, medium-chain triglycerides which show a faster metabolic clearance than long-chain triglycerides, and fish oil which provides the supply of omega-3 fatty acids. The utility of Omegaven and soy-based lipid emulsion is limited as these are restricted to 1 g/kg/day in cholestatic infants. SMOFlipid is safe to be provided at the usual goal infusion amount of 3 g/kg/day. Because this product includes both omega-6 and omega-3 lipids, it provides the benefits of the omega-3s for the liver and provides more than enough omega-6s to meet essential fatty acid requirements. Its use in situations in which growth is inadequate in babies who must be restricted to 1 g/kg/day can be expected to improve their growth and likely markedly increase their chances of both a good neurological outcome and survival. The aim of this research study is to determine if the unique formulation of SMOFLipid will cause less hepatic inflammation compared to soy only intralipids.
Detailed Description
The neonates who are being treated at the University of Florida Health Neonates Intensive Care Unit and are anticipated to need more than 21 days of intravenous nutrition will be considered as potential subjects. These subjects will receive the unique formulation of SMOFLipid The following data will be collected from the subject's EMR by members of the research team: Lab values that evaluate liver function Growth parameters like head circumference, length, weight Medical/surgical history Time to resolution of bilirubin, time to liver transplant, time to death Length of hospital stay Rates of blood infections Subjects will remain on SMOFlipid until weaned from PN.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholestasis, Jaundice, Obstructive
Keywords
Parenteral nutrition, Total, Infant, newborn, Cholestasis, Enterocolitis, Necrotizing

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SMOFlipid
Arm Type
Experimental
Arm Description
Subjects with cholestasis will receive 3 G/kg/day of intravenous SMOFlipid daily until parenteral nutrition (PN) is discontinued. In addition, the following monitoring for effects of SMOFlipid will be performed: total days of parenteral nutrition, maximum conjugated bilirubin, time to resolution of bilirubin, time to liver transplant, time to death, positive blood cultures, rates of increase in weight, length, and head circumference, time dependent changes in liver function tests, including triglycerides, and length of hospital stay.
Intervention Type
Drug
Intervention Name(s)
SMOFlipid
Other Intervention Name(s)
Parenteral nutrition (PN)
Intervention Description
SMOFlipid contains a mixture of 4 different lipid sources: soybean oil which provides essential fatty acids, olive oil which is high in monounsaturated fatty acids that are less susceptible to lipid peroxidation than polyunsaturated fatty acids, medium-chain triglycerides which show a faster metabolic clearance than long-chain triglycerides, and fish oil which provides the supply of omega-3 fatty acids.
Primary Outcome Measure Information:
Title
Inflammation of the Liver Between the Groups
Description
Inflammation of the liver will be evaluated by comparing direct bilirubin values between the two groups.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Measurement of Head Circumference for Growth Increase
Description
Growth increase will be measured by head circumference of participants.
Time Frame
6 months
Title
Measurement of Weight for Growth Increase
Description
Growth increase will be measured by weight of participants.
Time Frame
6 months
Title
Measurement of Length for Growth Increase
Description
Growth increase will be measured by length of participants.
Time Frame
6 months
Title
Number of Subjects Requiring Surgery
Time Frame
6 months
Title
Number of Concomitant Medications Received
Time Frame
6 months
Title
Length of IV Nutritional Therapy
Time Frame
6 months
Title
Number of Subjects Receiving Formula Diet
Description
Enteral administration of formula will be noted
Time Frame
6 months
Title
Number of Subjects Receiving Breast Milk Diet
Description
Enteral administration of breast milk will be noted
Time Frame
6 months
Title
Number of Participants With Adverse Events Related to Treatment
Description
Laboratory values will be used to determine adverse events.
Time Frame
6 months
Title
Carbon Dioxide Total
Description
Laboratory value that determines acid-base balance
Time Frame
6 months
Title
Total Protein
Description
Laboratory value that evaluates liver function
Time Frame
6 months
Title
Albumin
Description
Laboratory value that evaluates liver function
Time Frame
6 months
Title
Aspartate Aminotransferase
Description
Laboratory value that evaluates liver function
Time Frame
6 months
Title
Alanine Aminotransferase
Description
Laboratory value that evaluates liver function
Time Frame
6 months
Title
Total Bilirubin
Description
Laboratory value that evaluates liver function
Time Frame
6 months
Title
Serum Glucose
Description
Laboratory values that evaluates glucose in the blood
Time Frame
6 months
Title
Alkaline Phosphatase
Description
Laboratory value that evaluates liver function
Time Frame
6 months
Title
Triglyceride
Description
Laboratory value that evaluates liver function and metabolism of fat
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Number of Days on Mechanical Ventilation Via Endotracheal Tube
Description
Length of therapy with mechanical ventilation
Time Frame
6 months
Title
Number of Days on Oxygen Via Continuous Positive Airway Pressure
Description
Length of therapy with nasal continuous positive airway pressure
Time Frame
6 months
Title
Number of Days on Oxygen Via Nasal Cannula
Description
Length of therapy with nasal cannula
Time Frame
6 months
Title
Number of Days With Central Venous Catheter
Time Frame
6 months
Title
Number of Blood Infections
Description
A review of the subject's medical record will determine the presence of bacterial, viral, or fungi colony-forming units (CFU) in the blood.
Time Frame
6 months
Title
Numbers of Blood Infection Obtained From a Venipuncture
Description
A review of the subject's medical record will determine the location from which positive blood cultures were obtained.
Time Frame
6 months
Title
Numbers of Blood Infection Obtained From a Central Venous Catheter
Description
A review of the subject's medical record will determine the location from which positive blood cultures were obtained.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
23 Weeks
Maximum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Greater than 14 days old and less than 1 year of age. Greater than 1 kg. Mild cholestasis, defined as a conjugated bilirubin between 0.5-1.9 mg/dL Currently standard therapy with soy-based Intralipid Evidence of growth of weight, head circumference or length below our standards for post-menstrual age for at least 1 week. Be expected to require intravenous nutrition for at least an additional 21 days Exclusion Criteria: Have a congenitally lethal condition. Have clinically severe bleeding or clinical liver failure not able to be managed with routine measures. Have evidence of a viral hepatitis or primary liver disease as the primary etiology of their cholestasis. Have other health problems such that survival is extremely unlikely even if the infant's cholestasis improves
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Josef Neu, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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SMOFlipid to Lessen the Severity of Neonatal Cholestasis

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