Clinical trial NCT02420496: Enteral Fish Oil is Superior to Ursodeoxycholic Acid (UDCA) and Placebo for the Treatment of Cholestasis in Infants
Official title: Enteral Fish Oil is Superior to Ursodeoxycholic Acid (UDCA) and Placebo (?) for the Treatment of Cholestasis in Infants
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Cholestasis
Liver Disease
Keywords: Parental nutrition
associated
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2015-04-17
Enrollment: 0
Sex: ALL
Minimum age (years): 14
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate the effect of enteral fish oil and UDCA on the time of cholestasis resolution and other markers of parenteral nutrition-associated liver disease.


Eligibility criteria: Inclusion Criteria:

Neonates admitted to the Neonatal Intensive Care Unit (NICU) at University Hospital (UH) in San Antonio, Texas, who:

1. Are \>14 days old and \<24 months of age
2. Have a serum direct bilirubin of ≥2 mg/dL
3. Are receiving \<3 g/k/day of Intralipid via TPN
4. Are expected to remain hospitalized for at least an additional 21 days

Exclusion Criteria:

1. Have a congenitally lethal condition (e.g. Trisomy 13)
2. Have clinically severe bleeding not able to be managed with routine measures
3. Have evidence of a viral hepatitis or primary liver disease as the etiology of their cholestasis
4. Have other health problems such that survival is extremely unlikely even if cholestasis improves
5. Known allergy to eggs or fish products
6. Receiving IV Fish oil
7. Phenobarbital therapy at enrollment

Primary outcomes:
measure: Direct Bilirubin
timeFrame: Evaluated every 7 days up to 180 days
Secondary outcomes:
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: University Hospital
state: Texas
Study officials:
affiliation: University of Texas
name: Cynthia Blanco, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kelly DA. Liver complications of pediatric parenteral nutrition--epidemiology. Nutrition. 1998 Jan;14(1):153-7. doi: 10.1016/s0899-9007(97)00232-3.
citation: Christensen RD, Henry E, Wiedmeier SE, Burnett J, Lambert DK. Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease. J Perinatol. 2007 May;27(5):284-90. doi: 10.1038/sj.jp.7211686. Epub 2007 Mar 8.
citation: Nathan JD, Rudolph JA, Kocoshis SA, Alonso MH, Ryckman FC, Tiao GM. Isolated liver and multivisceral transplantation for total parenteral nutrition-related end-stage liver disease. J Pediatr Surg. 2007 Jan;42(1):143-7. doi: 10.1016/j.jpedsurg.2006.09.049.
citation: Colomb V, Jobert-Giraud A, Lacaille F, Goulet O, Fournet JC, Ricour C. Role of lipid emulsions in cholestasis associated with long-term parenteral nutrition in children. JPEN J Parenter Enteral Nutr. 2000 Nov-Dec;24(6):345-50. doi: 10.1177/0148607100024006345.
citation: Javid PJ, Greene AK, Garza J, Gura K, Alwayn IP, Voss S, Nose V, Satchi-Fainaro R, Zausche B, Mulkern RV, Jaksic T, Bistrian B, Folkman J, Puder M. The route of lipid administration affects parenteral nutrition-induced hepatic steatosis in a mouse model. J Pediatr Surg. 2005 Sep;40(9):1446-53. doi: 10.1016/j.jpedsurg.2005.05.045.
citation: Calder PC. Use of fish oil in parenteral nutrition: Rationale and reality. Proc Nutr Soc. 2006 Aug;65(3):264-77. doi: 10.1079/pns2006500.
citation: Clayton PT, Whitfield P, Iyer K. The role of phytosterols in the pathogenesis of liver complications of pediatric parenteral nutrition. Nutrition. 1998 Jan;14(1):158-64. doi: 10.1016/s0899-9007(97)00233-5.
citation: Alwayn IP, Andersson C, Zauscher B, Gura K, Nose V, Puder M. Omega-3 fatty acids improve hepatic steatosis in a murine model: potential implications for the marginal steatotic liver donor. Transplantation. 2005 Mar 15;79(5):606-8. doi: 10.1097/01.tp.0000150023.86487.44.
citation: Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP, Arsenault DA, Strijbosch RA, Lopes S, Duggan C, Puder M. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008 Mar;121(3):e678-86. doi: 10.1542/peds.2007-2248.
citation: Premkumar MH, Carter BA, Hawthorne KM, King K, Abrams SA. Fish oil-based lipid emulsions in the treatment of parenteral nutrition-associated liver disease: an ongoing positive experience. Adv Nutr. 2014 Jan 1;5(1):65-70. doi: 10.3945/an.113.004671.
citation: Chen CY, Tsao PN, Chen HL, Chou HC, Hsieh WS, Chang MH. Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis. J Pediatr. 2004 Sep;145(3):317-21. doi: 10.1016/j.jpeds.2004.05.038.
citation: Thibault M, McMahon J, Faubert G, Charbonneau J, Malo J, Ferreira E, Mohamed I. Parenteral nutrition-associated liver disease: a retrospective study of ursodeoxycholic Acid use in neonates. J Pediatr Pharmacol Ther. 2014 Jan;19(1):42-8. doi: 10.5863/1551-6776-19.1.42.
citation: Tillman EM, Crill CM, Black DD, Hak EB, Lazar LF, Christensen ML, Huang EY, Helms RA. Enteral fish oil for treatment of parenteral nutrition-associated liver disease in six infants with short-bowel syndrome. Pharmacotherapy. 2011 May;31(5):503-9. doi: 10.1592/phco.31.5.503.
citation: Yang Q, Ayers K, Welch CD, O'Shea TM. Randomized controlled trial of early enteral fat supplement and fish oil to promote intestinal adaptation in premature infants with an enterostomy. J Pediatr. 2014 Aug;165(2):274-279.e1. doi: 10.1016/j.jpeds.2014.02.002. Epub 2014 Mar 12.