Cholestasis Prevention: Efficacy of IV Fish Oil
- Conditions
- Parenteral NutritionCholestasis
- Interventions
- Registration Number
- NCT00512629
- Lead Sponsor
- Boston Children's Hospital
- Brief Summary
Parenteral nutrition (PN) solutions are life saving in patients with surgical gastrointestinal diseases. However, the use of PN in pediatric populations, especially premature infants, is frequently associated with liver injury that may ultimately result in hepatic failure. In studies conducted in a murine model, we observed that intravenous fat emulsions (IFE) comprised of omega-3 fatty acids were able to prevent the development of cholestasis, a common precursor of PN-associated liver disease, as well as reverse preexisting PNALD through a combination of factors, including improved triglyceride clearance coupled with anti-inflammatory properties. In a case series treating patients with hepatic cholestasis, serum bilirubin levels decreased markedly after the parenteral administration of an omega-3 fatty acid based fat emulsion (Omegaven®). Patients tolerated this therapy and no adverse reactions attributed to its use were observed. Based on results of these previous studies, we propose to conduct a randomized trial aiming to gain preliminary evidence of efficacy of an omega-3 fatty acid based IFE in preventing PNALD in children with intestinal failure
- Detailed Description
We propose to conduct a randomized controlled clinical trial to determine whether the use of an omega-3 fatty acid based IFE in infants with surgical gastrointestinal disease will improve clinical outcomes compared to infants treated with standard IFE up to 6 months post randomization. Neonates and infants \< 3 months old (postnatally) with surgical gastrointestinal disease (defined as congenital or acquired gastrointestinal disease requiring PN for more than 21 days) will be eligible for enrollment. Patients who meet all inclusion and exclusion criteria will be randomized to receive PN with either Intralipid® or Omegaven®. The appearance of both IFEs is indistinguishable, so patients, families and the medical care team will be blinded to treatment group allocation. Aside from the IFE type, the clinical care of both groups of infants will remain unchanged, including standard use of feeding advancement protocols, and treatment of underlying gastrointestinal and other diseases.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Intralipid Intralipid - Omegaven Omegaven Omegaven is a fish based intravenous fat emulsion
- Primary Outcome Measures
Name Time Method Presence vs. absence of PN-associated cholestasis (PNAC) 6 months The definition of "Presence vs. Absence of PNAC" will vary with the post conceptual age of the child. In infants \> 40 weeks post conceptual age, we will define PN-associated cholestasis as four consecutive measurements (\> 6 days apart) of serum direct bilirubin \> 2.0mg/dL obtained over a 30 day period in the absence of other demonstrable etiologies of cholestasis. Due to hepatic immaturity, for infants \< 40 weeks post conceptual age, PN associated cholestasis will be defined as four consecutive measurements (\> 6 days apart) of serum direct bilirubin \> 2.0mg/dL obtained over a 42 day period.
- Secondary Outcome Measures
Name Time Method Weight and height gain 6 months Liver function tests 6 months (i.e. serum triglycerides, cholesterol, ALT, AST and total and direct bilirubin levels)
Fatty acid profiles 6 months (i.e., Mead acid levels, triene:tetraene ratios, total omega-3 and omega-6 fatty acid levels, arachidonic acid levels)
Death from PNALD liver or liver/gastrointestinal tract transplant. 1 year Duration of parenteral nutrition 6 months (i.e. enteral feeding tolerance, including days to reach full enteral feeding (approximately 100-125kcal/kg/d + 10%) after randomization and the number of episodes of feeding intolerance (defined as an interruption of enteral feedings for \> 12 hrs) , number of infants requiring TPN providing \> 10% of total daily fluid volume at 12 weeks after randomization, and duration of TPN providing \> 10% of total daily fluid intake)
Frequency of blood stream infections 6 months Inflammatory markers (C-reactive protein), cytokine levels 6 months Incidence and severity of ROP 6 months Neurodevelopment Assessments 6, 12, & 24 months (corrected for gestational age) Neurodevelopment will be assessed at 6, 12, and 24 months (corrected) using Bayley Scales of Infant Development III(mean total, cognitive, language, and motor scaled score; and frequency of each score \<70). The MSD parent questionnaire will be mailed at 12 and 24 months (corrected); and the Parent Report of Children's Abilities - Revised (PARCA-R) parent questionnaire will be mailed at 24 months (coorected).
Trial Locations
- Locations (1)
Childrens's Hospital Boston
🇺🇸Boston, Massachusetts, United States