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

Short Bowel Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01739517
• Other study ID #: IND104555
• Status: Recruiting
• Phase: Phase 2
• First received: November 28, 2012
• Last updated: November 29, 2012
• Start date: March 2009
• Est. completion date: December 2013

Study information

• Verified date: November 2012
• Source: Amarnath, Rathna, M.D.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 1 Year

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cholestasis
• Liver Diseases
• Short Bowel Syndrome

Intervention

Drug:
• Omegaven Therapy
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.

Locations

Country	Name	City	State
United States	Palmetto Health Children's Hospital	Columbia	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Amarnath, Rathna, M.D.

Country where clinical trial is conducted

United States, 

References & Publications (11)

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. — View 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. Epub 2007 Mar 8. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View Citation

Kelly DA. Intestinal failure-associated liver disease: what do we know today? Gastroenterology. 2006 Feb;130(2 Suppl 1):S70-7. Review. — View 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. — View 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. — View 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	a) Maintenance of nutritional status	Nutritional status will be monitored by reviewing complete metabolic panel, magnesium, weight, vitals, phosphorus, prealbumin, lipid panel, and essential free fatty acid profile. The essential fatty acid profile will be checked at baseline and then monthly for at least 6 months until the patient is determined to be receiving at least 2.7% of caloric intake from linoleic acid. If the patient's essential fatty acid profile indicates that the patient is absorbing adequate amounts of essential fatty acid, the essential fatty acid profile will be discontinued .	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	No
Secondary	Occurrence of potential adverse side effects	Adverse events may include but are not limited to prolonged prothrombin time, hypertriglyceridemia, and anaphylaxis in relation to the patient's therapy.	biweekly labwork up to an expected average of 108 weeks	Yes
Secondary	c) Resolution of liver dysfunction	Resolution of liver dysfunction will be defined by achievement of normal direct bilirubin, aspartate aminotransferase and alanine transaminase.	weekly complete metabolic panel for the first month and then biweekly thereafter, up to an expected average of 108 weeks	No