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:
Participant gender:
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.