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

Primary Purpose

Short Bowel Syndrome, Cholestasis

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Omegaven Therapy

About this trial

This is an interventional treatment trial for Short Bowel Syndrome focused on measuring Short bowel syndrome, Cholestasis, Omegaven, Parenteral nutrition-associated Liver Disease

Eligibility Criteria

undefined - 1 Year (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Palmetto Health Children's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Omegaven Therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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 .

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.

c) Resolution of liver dysfunction

Resolution of liver dysfunction will be defined by achievement of normal direct bilirubin, aspartate aminotransferase and alanine transaminase.

Full Information

NCT ID

NCT01739517

First Posted

November 28, 2012

Last Updated

November 29, 2012

Sponsor

Amarnath, Rathna, M.D.

1. Study Identification

Unique Protocol Identification Number

NCT01739517

Brief Title

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

2. Study Status

Record Verification Date

November 2012

Overall Recruitment Status

Unknown status

Study Start Date

March 2009 (undefined)

Primary Completion Date

December 2013 (Anticipated)

Study Completion Date

December 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amarnath, Rathna, M.D.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Short Bowel Syndrome, Cholestasis

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Omegaven Therapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Omegaven Therapy

Intervention Description

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

weekly then biweekly data collection

Secondary Outcome Measure Information:

Title

a) Maintenance of nutritional status

Description

Time Frame

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

Title

Occurrence of potential adverse side effects

Description

Adverse events may include but are not limited to prolonged prothrombin time, hypertriglyceridemia, and anaphylaxis in relation to the patient's therapy.

Time Frame

biweekly labwork up to an expected average of 108 weeks

Title

c) Resolution of liver dysfunction

Description

Resolution of liver dysfunction will be defined by achievement of normal direct bilirubin, aspartate aminotransferase and alanine transaminase.

Time Frame

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

10. Eligibility

Sex

All

Maximum Age & Unit of Time

1 Year

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Terra R Varner, PharmD

Organizational Affiliation

Palmetto Health Children's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Palmetto Health Children's Hospital

City

Columbia

State/Province

South Carolina

ZIP/Postal Code

29203

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Terra R Varner, PharmD

Phone

803-434-3034

terra.varner@palmettohealth.org

First Name & Middle Initial & Last Name & Degree

Terra R Varner, PharmD

12. IPD Sharing Statement

Citations:

PubMed Identifier

17344923

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.

Results Reference

background

PubMed Identifier

18504595

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.

Results Reference

background

PubMed Identifier

16473076

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.

Results Reference

background

PubMed Identifier

16818533

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.

Results Reference

background

PubMed Identifier

8468653

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.

Results Reference

background

PubMed Identifier

16843991

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.

Results Reference

background

PubMed Identifier

20038849

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.

Results Reference

background

PubMed Identifier

11071594

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.

Results Reference

background

PubMed Identifier

16844003

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.

Results Reference

background

PubMed Identifier

18310188

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.

Results Reference

background

PubMed Identifier

19661785

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.

Results Reference

background

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

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