SMOFlipid to Lessen the Severity of Neonatal Cholestasis

NCT02721277 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: IRB201600068
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Cholestasis; Jaundice, Obstructive

Keywords

Parenteral nutrition, Total; Infant, newborn; Cholestasis; Enterocolitis, Necrotizing

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

• Measurement of Head Circumference for Growth Increase

  6 months

• Measurement of Weight for Growth Increase

  6 months

• Measurement of Length for Growth Increase

  6 months

• Number of Subjects Requiring Surgery

  6 months

• Number of Concomitant Medications Received

  6 months

Other Outcomes (7)

• Number of Days on Mechanical Ventilation Via Endotracheal Tube

  6 months

• Number of Days on Oxygen Via Continuous Positive Airway Pressure

  6 months

• Number of Days on Oxygen Via Nasal Cannula

  6 months

Study Arms (1)

SMOFlipid

EXPERIMENTAL

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

Interventions

SMOFlipid DRUG

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.

Also known as: Parenteral nutrition (PN)

SMOFlipid

Eligibility Criteria

• Age: 23 Weeks - 1 Year
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Cholestasis; Jaundice, Obstructive; Hyperphagia; Enterocolitis, Necrotizing

Interventions

SMOFlipid; Parenteral Nutrition

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Jaundice; Hyperbilirubinemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Signs and Symptoms, Digestive; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Feeding Methods; Therapeutics; Nutritional Support; Nutrition Therapy

Results Point of Contact

• Title: Josef Neu, MD
• Organization: University of Florida

neuj@peds.ufl.edu

352-273-8985

Study Officials

• Josef Neu, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2016
• First Posted: March 29, 2016
• Study Start: May 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: February 2, 2017
• Last Updated: April 17, 2017
• Results First Posted: April 17, 2017

Record last verified: 2017-03

Locations

US (1)