Clinical trial NCT02721277: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Cholestasis
Jaundice, Obstructive
Keywords: Parenteral nutrition, Total
Infant, newborn
Cholestasis
Enterocolitis, Necrotizing
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2016-03-29
Enrollment: 2
Sex: ALL
Minimum age (years): 23
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Inflammation of the Liver Between the Groups
timeFrame: 6 months
Secondary outcomes:
measure: Measurement of Head Circumference for Growth Increase
timeFrame: 6 months
measure: Measurement of Weight for Growth Increase
timeFrame: 6 months
measure: Measurement of Length for Growth Increase
timeFrame: 6 months
measure: Number of Subjects Requiring Surgery
timeFrame: 6 months
measure: Number of Concomitant Medications Received
timeFrame: 6 months
measure: Length of IV Nutritional Therapy
timeFrame: 6 months
measure: Number of Subjects Receiving Formula Diet
timeFrame: 6 months
measure: Number of Subjects Receiving Breast Milk Diet
timeFrame: 6 months
measure: Number of Participants With Adverse Events Related to Treatment
timeFrame: 6 months
measure: Carbon Dioxide Total
timeFrame: 6 months
measure: Total Protein
timeFrame: 6 months
measure: Albumin
timeFrame: 6 months
measure: Aspartate Aminotransferase
timeFrame: 6 months
measure: Alanine Aminotransferase
timeFrame: 6 months
measure: Total Bilirubin
timeFrame: 6 months
measure: Serum Glucose
timeFrame: 6 months
measure: Alkaline Phosphatase
timeFrame: 6 months
measure: Triglyceride
timeFrame: 6 months
Other outcomes:
measure: Number of Days on Mechanical Ventilation Via Endotracheal Tube
timeFrame: 6 months
measure: Number of Days on Oxygen Via Continuous Positive Airway Pressure
timeFrame: 6 months
measure: Number of Days on Oxygen Via Nasal Cannula
timeFrame: 6 months
measure: Number of Days With Central Venous Catheter
timeFrame: 6 months
measure: Number of Blood Infections
timeFrame: 6 months
measure: Numbers of Blood Infection Obtained From a Venipuncture
timeFrame: 6 months
measure: Numbers of Blood Infection Obtained From a Central Venous Catheter
timeFrame: 6 months
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Josef Neu, MD
role: PRINCIPAL_INVESTIGATOR
References: