Effect of Nitric Oxide (NO) on Ischemic/Reperfusion Injury During Extended Donor Criteria (EDC) Liver Transplantation

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by University of Colorado, Denver.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00948194
First received: July 24, 2009
Last updated: February 20, 2013
Last verified: July 2009
  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(EDC)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 EDC 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 International Normalized Ratio (INR) bilirubin, transaminases, and duration of hospital stay.

Hypothesis 2: The mechanisms of therapeutic efficacy of inhaled nitric oxide is based on reduction in post-reperfusion oxidative injury as readily measured by the detectable changes in the protein and metabolic profiles in plasma of patients treated with inhaled-NO

  • Nuclear Magnetic Resonance (NMR)-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.

Condition Intervention
Liver Transplantation
Ischemia/Reperfusion Injury
Oxidative Injury
Drug: Nitric Oxide

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Investigation of the Effect of Nitric Oxide on Ischemic Reperfusion Injury During Extended Donor Criteria Liver Transplantation

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To construct a plasma metabolic/protein profile of I/R injury in transplanted livers [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To examine the effects of nitric oxide on protein synthesis and metabolism following ECD liver transplantation [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: October 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: No nitric oxide
This arm will not receive nitric oxide, but will receive other standard inhaled anesthetics
Experimental: Nitric Oxide
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
Other Name: INOmax

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
Contact: Colleen Dingmann, R.N., Ph.D. 720-848-6751 Colleen.Dingmann@ucdenver.edu

Locations
United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Matthew Fiegel, M.D.         
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Matthew J. Fiegel, M.D. University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00948194     History of Changes
Other Study ID Numbers: 09-0137
Study First Received: July 24, 2009
Last Updated: February 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
Extended Donor Criteria

Additional relevant MeSH terms:
Ischemia
Reperfusion Injury
Wounds and Injuries
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents

ClinicalTrials.gov processed this record on April 16, 2014