Purpose

In this study, the researchers propose to investigate the efficacy of inhaled nitric oxide to prevent ischemia-reperfusion (I/R) hepatocyte injury in patients who receive extended donor criteria liver grafts based on changes in proteomic and metabolomic markers following revascularization of the donor graft.
In reviewing the literature, no uniform extended criteria donor classification exists. The characteristics most associated with liver graft failure appear to be cold ischemia time greater than 10 hours, warm ischemia time greater than 40 minutes, donor age > 55 years of age, donor hospitalization > 5 days, a donation after cardiac death (DCD) graft, and a split graft. The researchers will exclude warm ischemia time as this is impossible to predict prior to the transplantation. Any donor meeting at least one of the other criteria will be classified as an ECD donor.
Hypothesis 1: Inhaled nitric oxide will improve overall outcome of liver recipients after EDC liver transplantation

• Suppression of oxidative injury will improve graft function postoperatively as measured by INR, bilirubin, transaminases, and duration of hospital stay.
  

• NMR (nuclear magnetic resonance)-based metabolic markers (xanthine end-products, lactate, and hepatic osmolytes) that are consistent with acute liver injury will be decreased in NO-treated recipients.
  
• Protein markers of reperfusion injury (argininosuccinate synthase (ASS) and estrogen sulfotransferase (EST-1) will be greater in the plasma of patients who are not treated with inhaled-NO
• Reduced oxidative injury will be reflected by a decrease in the number of mitochondrial peroxiredoxins isoforms and the number that are oxidized in NO-treated liver recipients.
  
  
  

  status:	not yet recruiting
  conditions:	Liver Transplantation ; Ischemia/Reperfusion Injury ; Oxidative Injury
  interventions:	Nitric Oxide
  phase:	N/A
  study type:	Interventional
  study design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
  official title:	Investigation of the Effect of Nitric Oxide on Ischemic Reperfusion Injury During Extended Donor Criteria Liver Transplantation

• Further study details (as provided by University of Colorado at Denver and Health Sciences Center)

  primary outcome measures:

  • To determine if inhaled nitric oxide has beneficial effects on overall outcome after extended criteria donor (EDC)liver transplantation [ Time Frame: 3 years ]

  secondary outcome measures:

  • To construct a plasma metabolic/protein profile of I/R injury in transplanted livers [ Time Frame: 3 years ]
  • To examine the effects of nitric oxide on protein synthesis and metabolism following ECD liver transplantation [ Time Frame: 3 years ]

  enrollment: 20

  study start date: September 2009

  study completion date: September 2012

  
  

  Arms	Assigned Interventions
  No nitric oxide: No Intervention This arm will not receive nitric oxide, but will receive other standard inhaled anesthetics	No intervention
  Nitric Oxide: Experimental Will receive Nitric oxide and other standard inhaled anesthetics	Drug: Nitric Oxide Inhalation - 40 ppm, at the initiation of anesthesia to the end of surgery

• Eligibility

  ages eligible for study:	18 Years to 69 Years
  genders eligible for study:	Both

  Criteria

  Inclusion Criteria:
  

  • Age 18 - 69 years of age
  • moderate to severe liver disease (MELD score 22 to 30)
  • is receiving a extended donor criteria liver graft

  
  Exclusion Criteria:
  

  • undergoing multi-organ transplant
  • 70 years or older
  • diagnosed with hepatocarcinoma
  • diagnosed with either hepatopulmonary syndrome or pulmonary hypertension
  • pregnant

• Contacts and locations

  Please refer to this study by its ClinicalTrials.gov identifier: NCT00948194

  Contacts

  Colleen Dingmann, R.N., Ph.D.   720-848-6751   Colleen.Dingmann@ucdenver.edu

  Locations

  United States , Colorado  - University of Colorado Hospital

  facility:

  Aurora, Colorado, United States, 80045

  
  

• Sponsors and collaborators

  University of Colorado at Denver and Health Sciences Center
  

  investigators:

  Matthew J. Fiegel, M.D., Principal Investigator, University of Colorado Denver

• More information

  first received:	July 24, 2009
  last updated:	July 28, 2009
  ClinicalTrials.gov Identifier:	NCT00948194
  health authority:	United States: Food and Drug Administration

Information obtained from ClinicalTrials.gov on September 25, 2009   Link to the current ClinicalTrials.gov record.

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