SMOFlipid to Lessen the Severity of Neonatal Cholestasis

Phase 1

Terminated

• Conditions: Cholestasis; Jaundice, Obstructive
• Interventions: Drug: SMOFlipid

• Registration Number: NCT02721277
• Lead Sponsor: University of Florida

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.

Study Timeline

• Study First Submitted: 2016-02-23
• Study First Submitted QC: 2016-03-22
• Study First Posted: 2016-03-29
• Study Start: 2016-05
• Primary Completion: 2016-12
• Study Completion: 2017-02-02
• Status Verified: 2017-03
• Results First Submitted: 2017-03-03
• Results First Submitted QC: 2017-03-03
• Last Update Submitted: 2017-03-03
• Results First Posted: 2017-04-17
• Last Update Posted: 2017-04-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SMOFlipid	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.

Primary Outcome Measures

Name	Time	Method
Inflammation of the Liver Between the Groups	6 months	Inflammation of the liver will be evaluated by comparing direct bilirubin values between the two groups.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Florida; 🇺🇸 Gainesville, Florida, United States