Parenteral Nutrition Associated Liver Disease: Early Markers and Therapy Wih Enteral Omega-3 Supplementation

• Status: Unknown status
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Cholestatic liver disease is a common complication associated with long term parenteral nutrition (PN). PN associated liver disease (PNALD) is much more common in premature infants and the incidence increases with duration of PN. The use of intravenous omega-3 long chain polyunsaturated fatty acids (ω3PUFA) or fish oil has recently shown promise in the treatment of PNALD. We hypothesize that there are early markers for PNALD that precede the increase in total and direct bilirubin. We further hypothesize that patients with PNALD who receive enteral ω3PUFA supplementation will have an improvement in PNALD or reversal of PNALD. These hypotheses will be tested by a two part study that includes an initial observation period when markers for PNALD are evaluated, followed by a randomized, controlled trial of enteral ω3PUFA supplementation for treatment of PNALD. Infants expected to be on PN for 4 weeks or longer will be eligible for enrollment in this study. The observational part of the study will entail periodic assessment of potential markers for PNALD. Markers will be evaluated for inflammatory cytokines (IL-1, IL-6, TNF-alpha), oxidative stress (8-isoprostane, 8-hydroxydeoxyguanosine, glutathione peroxidase), liver fibrosis (TIMP-1), endogenous steroid production (glucagon and ACTH), total serum bile acids, essential fatty acid profiles, and calprotectin, a novel marker of gut inflammation. Patients will be observed for 6 months duration. Patients enrolled in the study who develop PNALD will be randomized to either the current standard of care (control group) or enteral ω3PUFA supplementation (treatment group). Once able to take oral medications, treatment group patients will receive enteral ω3PUFA 1 g/kg/day for 12 weeks. At the end of the 12 weeks, the protocol will be open label in which any patients who continue to have PNALD in either group will receive enteral ω3PUFA. All patients enrolled in the study (whether or not they develop PNALD or receive ω3PUFA supplementation) will be followed for a total of 6 months. The results of this study will increase our knowledge of the pathogenesis of PNALD, as well as potentially confirm the effectiveness of a novel therapy for this costly and debilitating disease.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Tennessee

Criteria

Inclusion Criteria:

• Neonates / infants < 1 year of age (there is no minimum age for enrollment and subjects may be male or female)

• Enrolled prior to the development of PNALD

• Anticipated duration of PN of 4 weeks or greater including patients with:

• Short bowel syndrome resulting from surgical management of NEC, congenital bowel defects (omphalocele and gastroschisis), intestinal atresias, midgut volvulus, and other intestinal processes

• Functional short bowel syndrome

• Subjects must be deemed clinically stable with a life expectancy of at least 6 months before enrollment

Exclusion Criteria:

• Bleeding risk (platelets count < 50 thousand units/μL)

• Receiving aspirin or other anticoagulation agent

• Patient's who are deemed clinically unstable:

• Severe multi-system disease

• Genetic disorders

• DNR