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

NCT01157780 | Unknown

• 1 other identifier: 128695
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Parenteral Nutrition Associated Liver Disease

Keywords

Fish oil

Outcome Measures

Primary Outcomes (1)

• Determine if enteral ω3PUFA supplementation is effective for the treatment and/or reversal of PNALD.

  In order to answer our this objective, we will conduct a randomized controlled trial of enteral ω3PUFA supplementation in patients that develop PNALD. We will evaluate direct bilirubin, AST, ALT, and clinical presentation as outcomes as success of enteral ω3PUFA supplementation. We will evaluate baseline and serial fatty acid analysis to show that enteral fish oil is absorbed and effecting ω3PUFA concentrations. We will evaluate resolution of PNALD in patients receiving ω3PUFA compared to patients not supplimented with ω3PUFA. Time to resolution of disease will also be evaluated.

  3 years for study completion, 12 weeks per patients

Secondary Outcomes (1)

• Evaluate serum markers that may be early indicators of PNALD in infants receiving long term PN.

  3 years for total study, 6 months per patient

Study Arms (2)

fish oil

EXPERIMENTAL

When a subject develops PNALD (three consecutive direct bilirubin concentrations \> 2 mg/dL), and is able to tolerate at least trophic feeds (1 mL Q12h), the subject will be randomized to either the control group (our current hospital practice including advancement of enteral feeding, ursodiol, and cyclic PN, but not ω3PUFA) or the active treatment group (current hospital practice plus the addition of enteral ω3PUFA supplementation of 1 g/kg/day with a maximum dose of 4 g/day for a 12 week period). All patients will be started at 1 g/kg/day with a maximum dose of 4 g/day.

Drug: Lovaza (fish oil)

standard of care

NO INTERVENTION

When a subject develops PNALD (three consecutive direct bilirubin concentrations \> 2 mg/dL), and is able to tolerate at least trophic feeds (1 mL Q12h), the subject will be randomized to either the control group (our current hospital practice including advancement of enteral feeding, ursodiol, and cyclic PN, but not ω3PUFA) or the active treatment group (current hospital practice plus the addition of enteral ω3PUFA supplementation of 1 g/kg/day with a maximum dose of 4 g/day for a 12 week period). All patients will be started at 1 g/kg/day with a maximum dose of 4 g/day.

Interventions

Lovaza (fish oil) DRUG

Patients will receive fish supplementation of 1 g/kg/day with a maximum dose of 4 g/day for a 12 week period.

Also known as: Lovaza

fish oil

Eligibility Criteria

• Age: 1 Day - 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Tennessee: lead

Study Sites (1)

Le Bonheur Children's Medical Center

Memphis, Tennessee, 38103, United States

RECRUITING

MeSH Terms

Interventions

Omacor; Fish Oils

Intervention Hierarchy (Ancestors)

Oils; Lipids

Study Officials

• Emma Tillman, PharmD

  University of Tennessee

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emma M Tillman, PharmD

CONTACT

(901)287-5349; etillman@uthsc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 30, 2010
• First Posted: July 7, 2010
• Study Start: October 1, 2008
• Primary Completion: June 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 17, 2011

Record last verified: 2011-06

Locations

US (1)