SMOFlipid to Lessen the Severity of Neonatal Cholestasis

Cholestasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02721277
• Other study ID #: IRB201600068
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 23, 2016
• Last updated: December 21, 2016
• Start date: May 2016
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 23 Weeks to 1 Year

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Cholestasis
• Jaundice
• Jaundice, Obstructive

Intervention

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.

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of days on mechanical ventilation via endotracheal tube	Length of therapy with mechanical ventilation	6 months	No
Other	Number of days on oxygen via continuous positive airway pressure	Length of therapy with nasal continuous positive airway pressure	6 months	No
Other	Number of days on oxygen via nasal cannula	Length of therapy with nasal cannula	6 months	No
Other	Number of days with central venous catheter		6 months	No
Other	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	Yes
Other	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	Yes
Other	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	Yes
Primary	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	Yes
Secondary	Measurement of head circumference for growth increase	Growth increase will be measured by head circumference of participants.	6 months	No
Secondary	Measurement of weight for growth increase	Growth increase will be measured by weight of participants.	6 months	No
Secondary	Measurement of length for growth increase	Growth increase will be measured by length of participants.	6 months	No
Secondary	Number of subjects requiring surgery		6 months	No
Secondary	Number of concomitant medications received		6 months	No
Secondary	Length of IV nutritional therapy		6 months	No
Secondary	Number of subjects receiving formula diet	Enteral administration of formula will be noted	6 months	No
Secondary	Number of subjects receiving breast milk diet	Enteral administration of breast milk will be noted	6 months	No
Secondary	Number of participants with adverse events related to treatment	Laboratory values will be used to determine adverse events.	6 months	Yes
Secondary	Carbon Dioxide Total	Laboratory value that determines acid-base balance	6 months	Yes
Secondary	Total protein	Laboratory value that evaluates liver function	6 months	Yes
Secondary	Albumin	Laboratory value that evaluates liver function	6 months	Yes
Secondary	Aspartate aminotransferase	Laboratory value that evaluates liver function	6 months	Yes
Secondary	Alanine aminotransferase	Laboratory value that evaluates liver function	6 months	Yes
Secondary	Total Bilirubin	Laboratory value that evaluates liver function	6 months	Yes
Secondary	Serum Glucose	Laboratory values that evaluates glucose in the blood	6 months	No
Secondary	Alkaline phosphatase	Laboratory value that evaluates liver function	6 months	Yes
Secondary	Triglyceride	Laboratory value that evaluates liver function and metabolism of fat	6 months	Yes