SMOFlipid to Lessen the Severity of Neonatal Cholestasis

University of Florida

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Jaundice, Obstructive; Cholestasis

Treatments: Drug: SMOFlipid

Study type: Interventional

Funder types: Other

Identifiers

NCT02721277

IRB201600068

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2 patients

Sex: All

Ages: 23 weeks to 1 year old

Volunteers: Accepts 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

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

SMOFlipid

Experimental group

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.

Treatment:

Drug: SMOFlipid