SMOFlipid to Lessen the Severity of Neonatal Cholestasis

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

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.

Study Overview

• Status: Terminated
• Conditions: Cholestasis; Jaundice, Obstructive
• Intervention / Treatment: Drug: SMOFlipid

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 1 year (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: SMOFlipid; 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.

Drug: SMOFlipid; 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.; Other Names: Parenteral nutrition (PN)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammation of the Liver Between the Groups	Inflammation of the liver will be evaluated by comparing direct bilirubin values between the two groups.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Head Circumference for Growth Increase	Growth increase will be measured by head circumference of participants.	6 months
Measurement of Weight for Growth Increase	Growth increase will be measured by weight of participants.	6 months
Measurement of Length for Growth Increase	Growth increase will be measured by length of participants.	6 months
Number of Subjects Requiring Surgery		6 months
Number of Concomitant Medications Received		6 months
Length of IV Nutritional Therapy		6 months
Number of Subjects Receiving Formula Diet	Enteral administration of formula will be noted	6 months
Number of Subjects Receiving Breast Milk Diet	Enteral administration of breast milk will be noted	6 months
Number of Participants With Adverse Events Related to Treatment	Laboratory values will be used to determine adverse events.	6 months
Carbon Dioxide Total	Laboratory value that determines acid-base balance	6 months
Total Protein	Laboratory value that evaluates liver function	6 months
Albumin	Laboratory value that evaluates liver function	6 months
Aspartate Aminotransferase	Laboratory value that evaluates liver function	6 months
Alanine Aminotransferase	Laboratory value that evaluates liver function	6 months
Total Bilirubin	Laboratory value that evaluates liver function	6 months
Serum Glucose	Laboratory values that evaluates glucose in the blood	6 months
Alkaline Phosphatase	Laboratory value that evaluates liver function	6 months
Triglyceride	Laboratory value that evaluates liver function and metabolism of fat	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Days on Mechanical Ventilation Via Endotracheal Tube	Length of therapy with mechanical ventilation	6 months
Number of Days on Oxygen Via Continuous Positive Airway Pressure	Length of therapy with nasal continuous positive airway pressure	6 months
Number of Days on Oxygen Via Nasal Cannula	Length of therapy with nasal cannula	6 months
Number of Days With Central Venous Catheter		6 months
Number of Blood Infections	A review of the subject's medical record will determine the presence of bacterial, viral, or fungi colony-forming units (CFU) in the blood.	6 months
Numbers of Blood Infection Obtained From a Venipuncture	A review of the subject's medical record will determine the location from which positive blood cultures were obtained.	6 months
Numbers of Blood Infection Obtained From a Central Venous Catheter	A review of the subject's medical record will determine the location from which positive blood cultures were obtained.	6 months

Collaborators and Investigators

• Sponsor: University of Florida

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2016
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): February 2, 2017

Study Registration Dates

• First Submitted: February 23, 2016
• First Submitted That Met QC Criteria: March 22, 2016
• First Posted (ESTIMATE): March 29, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 17, 2017
• Last Update Submitted That Met QC Criteria: March 3, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Cholestasis; Enterocolitis, Necrotizing; Infant, newborn; Parenteral nutrition, Total
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Skin Manifestations; Biliary Tract Diseases; Bile Duct Diseases; Hyperbilirubinemia; Cholestasis; Jaundice; Jaundice, Obstructive; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; SMOFlipid
• Other Study ID Numbers: IRB201600068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No