Enteral Fish Oil is Superior to Ursodeoxycholic Acid (UDCA) and Placebo for the Treatment of Cholestasis in Infants

NCT02420496 | Withdrawn Phase 2 DMC

• 1 other identifier: HSC20150165H
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Cholestasis; Liver Disease

Keywords

Parental nutrition; associated

Outcome Measures

Primary Outcomes (1)

• Direct Bilirubin

  Direct bilirubin less than 1 mg/dL considered resolution of cholestasis

  Evaluated every 7 days up to 180 days

Study Arms (3)

Enteral fish oil

EXPERIMENTAL

Infants will receive enteral fish oil at a dose of 1mg/kg/day divided in two daily doses given enterally.

Drug: Enteral fish oil

UDCA (ursodeoxycholic acid)

ACTIVE COMPARATOR

Infants will receive UDCA at a dose of 10mg/kg/dose in two daily doses given enterally

Drug: Ursodeoxycholic Acid

Placebo

PLACEBO COMPARATOR

Infant will receive placebo in two daily doses given enterally

Drug: Placebo

Interventions

Enteral fish oil DRUG

Also known as: Nordic Natural Omega 3

Enteral fish oil

Ursodeoxycholic Acid DRUG

Also known as: Actigall

UDCA (ursodeoxycholic acid)

Placebo DRUG

Also known as: Sterile Water

Placebo

Eligibility Criteria

• Age: 14 Days - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Neonates admitted to the Neonatal Intensive Care Unit (NICU) at University Hospital (UH) in San Antonio, Texas, who:
• Are \>14 days old and \<24 months of age
• Have a serum direct bilirubin of ≥2 mg/dL
• Are receiving \<3 g/k/day of Intralipid via TPN
• Are expected to remain hospitalized for at least an additional 21 days

You may not qualify if:

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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

University Hospital

San Antonio, Texas, 78229, United States

Location

Related Publications (14)

• Kelly DA. Liver complications of pediatric parenteral nutrition--epidemiology. Nutrition. 1998 Jan;14(1):153-7. doi: 10.1016/s0899-9007(97)00232-3.

  PMID: 9437702 BACKGROUND

• 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

• 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.

  PMID: 17208555 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

• 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.

  PMID: 16150347 BACKGROUND

• 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.

  PMID: 16923311 BACKGROUND

• 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.

  PMID: 9437703 BACKGROUND

• 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.

  PMID: 15753852 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

• 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.

  PMID: 24425724 BACKGROUND

• 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.

  PMID: 15343182 BACKGROUND

• 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.

  PMID: 24782691 BACKGROUND

• 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.

  PMID: 21923431 BACKGROUND

• 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.

  PMID: 24630347 BACKGROUND

MeSH Terms

Conditions

Cholestasis; Liver Diseases

Interventions

Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Cynthia Blanco, M.D.

  University of Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2015
• First Posted: April 17, 2015
• Study Start: June 1, 2016
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: June 21, 2016

Record last verified: 2016-06

Locations

US (1)