Effect of Nitric Oxide (N.O.) on Ischemic/Reperfusion Injury During Extended Donor Criteria (EDC) Liver Transplantation - Full Text View

Sponsor:	University of Colorado, Denver
Information provided by:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT00948194

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.

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

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.

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:

MedlinePlus related topics: Liver Transplantation

Drug Information available for: Nitric oxide

U.S. FDA Resources

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:	October 2012
Estimated Primary Completion Date:	October 2012 (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:	Matthew Fiegel, M.D., University of Colorado - Denver, School of Medicine, Dept. of Anesthesiology
ClinicalTrials.gov Identifier:	NCT00948194 History of Changes
Other Study ID Numbers:	09-0137
Study First Received:	July 24, 2009
Last Updated:	October 5, 2009
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
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 May 24, 2012