Effect of Nitric Oxide (NO) on Ischemic/Reperfusion Injury During Extended Donor Criteria (EDC) Liver Transplantation
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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 |
- 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 ]
- 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 |
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| 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. | |
| 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 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 22, 2013