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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by University of Colorado, Denver
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
First received: July 24, 2009
Last updated: May 26, 2015
Last verified: May 2015

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 2015
Estimated Primary Completion Date: November 2015 (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


Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

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
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: May 26, 2015
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on November 30, 2015