Clinical trial NCT01739517: Efficacy and Safety of Omega-3 Lipid Therapy in Pediatric Patients With Parenteral Nutrition-Associated Liver Disease
Official title: Efficacy and Safety of Omega-3 Lipid Therapy in Pediatric Patients With Parenteral Nutrition-Associated Liver Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Short Bowel Syndrome
Cholestasis
Keywords: Short bowel syndrome
Cholestasis
Omegaven
Parenteral nutrition-associated Liver Disease
Lead sponsor: Amarnath, Rathna, M.D.
Sponsor class: INDIV
First posted: 2012-12-03
Enrollment: 20
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This pilot study seeks to demonstrate the efficacy of an intravenous lipid preparation high in omega-3 fatty acids (Omegaven) in the treatment of cholestasis in parenteral nutrition dependent patients with short gut syndrome.


Eligibility criteria: Inclusion Criteria:

* Patient will be dependent upon parenteral nutrition (PN)
* Patient will have short gut syndrome (loss of \>50% of small bowel)
* Patient's guardian/caregiver provides informed consent for patient to receive therapy
* Pediatric patient ≤ 1 year of age
* Expected PN duration is greater than 30 days
* Direct bilirubin \>2.0 mg/dL measured on two occasions no more than one week apart

Exclusion Criteria:

* Liver dysfunction secondary to cause other than PN verified by standard of care diagnostic procedures and lab work to rule out alternative causes of neonatal cholestasis.
* Any patient in whom Omegaven therapy would be contraindicated, such as an allergy to any seafood product, egg protein, and/or previously established allergy to Omegaven
* impaired lipid metabolism
* severe hemorrhagic disorder
* unstable diabetes mellitus
* collapse and shock, stroke/embolism, recent cardiac infarction, or undefined coma status

Primary outcomes:
measure: Improvement of liver dysfunction as measured by time to achieve 50 % decrease in direct bilirubin
timeFrame: weekly then biweekly data collection
Secondary outcomes:
measure: a) Maintenance of nutritional status
timeFrame: Labwork will be collected at baseline, then weekly for the first month. Thereafter, a lipid panel will be collected every 2 months, complete metabolic panel every 2 weeks, and essential fatty acid profile monthly, up to an expected average of 108 weeks
measure: Occurrence of potential adverse side effects
timeFrame: biweekly labwork up to an expected average of 108 weeks
measure: c) Resolution of liver dysfunction
timeFrame: weekly complete metabolic panel for the first month and then biweekly thereafter, up to an expected average of 108 weeks
Other outcomes:
Locations:
city: Columbia
country: United States
facility: Palmetto Health Children's Hospital
state: South Carolina
Study officials:
affiliation: Palmetto Health Children's Hospital
name: Terra R Varner, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
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: Diamond IR, Sterescu A, Pencharz PB, Wales PW. The rationale for the use of parenteral omega-3 lipids in children with short bowel syndrome and liver disease. Pediatr Surg Int. 2008 Jul;24(7):773-8. doi: 10.1007/s00383-008-2174-0. Epub 2008 May 27.
citation: Kelly DA. Intestinal failure-associated liver disease: what do we know today? Gastroenterology. 2006 Feb;130(2 Suppl 1):S70-7. doi: 10.1053/j.gastro.2005.10.066.
citation: Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR, Puder M. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics. 2006 Jul;118(1):e197-201. doi: 10.1542/peds.2005-2662.
citation: Moss RL, Das JB, Ansari G, Raffensperger JG. Hepatobiliary dysfunction during total parenteral nutrition is caused by infusate, not the route of administration. J Pediatr Surg. 1993 Mar;28(3):391-6; discussion 396-7. doi: 10.1016/0022-3468(93)90238-g.
citation: Chen WJ, Yeh SL, Huang PC. Effects of fat emulsions with different fatty acid composition on plasma and hepatic lipids in rats receiving total parenteral nutrition. Clin Nutr. 1996 Feb;15(1):24-8. doi: 10.1016/s0261-5614(96)80257-3.
citation: de Meijer VE, Le HD, Meisel JA, Gura KM, Puder M. Parenteral fish oil as monotherapy prevents essential fatty acid deficiency in parenteral nutrition-dependent patients. J Pediatr Gastroenterol Nutr. 2010 Feb;50(2):212-8. doi: 10.1097/MPG.0b013e3181bbf51e.
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: Yeh SL, Chen WJ, Huang PC. Effects of fish oil and safflower oil emulsions on diet-induced hepatic steatosis in rats receiving total parenteral nutrition. Clin Nutr. 1996 Apr;15(2):80-3. doi: 10.1016/s0261-5614(96)80024-0.
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: Puder M, Valim C, Meisel JA, Le HD, de Meijer VE, Robinson EM, Zhou J, Duggan C, Gura KM. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg. 2009 Sep;250(3):395-402. doi: 10.1097/SLA.0b013e3181b36657.