SMOFlipid to Lessen the Severity of Neonatal Cholestasis

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Cholestasis, Jaundice, Obstructive

Intervention / Treatment
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* Drug: SMOFlipid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 23 Weeks
Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SMOFlipid<br>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<br>* 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.<br>* Other names: Parenteral nutrition (PN);|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parenteral nutrition, Total, Infant, newborn, Cholestasis, Enterocolitis, Necrotizing