Efficacy and Safety of Omega-3 Lipid Therapy in Pediatric Patients With Parenteral Nutrition-Associated Liver Disease

NCT01739517 | Unknown Phase 2 DMC

• 1 other identifier: IND104555
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Short Bowel Syndrome; Cholestasis

Keywords

Short bowel syndrome; Cholestasis; Omegaven; Parenteral nutrition-associated Liver Disease

Outcome Measures

Primary Outcomes (1)

• Improvement of liver dysfunction as measured by time to achieve 50 % decrease in direct bilirubin

  Direct bilirubin will be collected at baseline, then weekly for 30 days, and then biweekly, thereafter, up to an expected average of 108 weeks

  weekly then biweekly data collection

Secondary Outcomes (3)

• a) Maintenance of nutritional status

  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

• Occurrence of potential adverse side effects

  biweekly labwork up to an expected average of 108 weeks

• c) Resolution of liver dysfunction

  weekly complete metabolic panel for the first month and then biweekly thereafter, up to an expected average of 108 weeks

Study Arms (1)

Omegaven Therapy

EXPERIMENTAL

After baseline labs, which have been collected no earlier than seven days prior to the initiation of therapy are obtained, therapy with Omegaven will be initiated at a starting dose of 0.5 g/kg/day infused over 12 hours. If tolerated, the dose will be increased to 1 g/kg/day, the goal dose. Omegaven will be infused intravenously through either a central or peripheral catheter in conjunction with parenteral nutrition.

Drug: Omegaven Therapy

Interventions

Omegaven Therapy DRUG

After baseline labs, which have been collected no earlier than seven days prior to the initiation of therapy are obtained, therapy with Omegaven will be initiated at a starting dose of 0.5 g/kg/day infused over 12 hours. If tolerated, the dose will be increased to 1 g/kg/day, the goal dose. Omegaven will be infused intravenously through either a central or peripheral catheter in conjunction with parenteral nutrition.

Omegaven Therapy

Eligibility Criteria

• Age: Up to 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amarnath, Rathna, M.D.: lead

Study Sites (1)

Palmetto Health Children's Hospital

Columbia, South Carolina, 29203, United States

RECRUITING

Related Publications (11)

• 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.

  PMID: 17344923 BACKGROUND

• 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.

  PMID: 18504595 BACKGROUND

• 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.

  PMID: 16473076 BACKGROUND

• 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.

  PMID: 16818533 BACKGROUND

• 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.

  PMID: 8468653 BACKGROUND

• 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.

  PMID: 16843991 BACKGROUND

• 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.

  PMID: 20038849 BACKGROUND

• 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.

  PMID: 11071594 BACKGROUND

• 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.

  PMID: 16844003 BACKGROUND

• 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.

  PMID: 18310188 BACKGROUND

• 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.

  PMID: 19661785 BACKGROUND

MeSH Terms

Conditions

Short Bowel Syndrome; Cholestasis

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bile Duct Diseases; Biliary Tract Diseases

Study Officials

• Terra R Varner, PharmD

  Palmetto Health Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2012
• First Posted: December 3, 2012
• Study Start: March 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 3, 2012

Record last verified: 2012-11

Locations

US (1)