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The Effects of Glucose/Ischemic Preconditioning on Reperfusion Injury in Deceased-Donor Liver Transplantation

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ClinicalTrials.gov Identifier: NCT00718575
Recruitment Status : Terminated (too few patients meeting current eligibility criteria)
First Posted : July 18, 2008
Last Update Posted : July 25, 2014
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Standard liver retrieval procedures for transplantation from a deceased donor inevitably result in a "reperfusion injury" to the liver tissue. The purpose of this research study is to find out whether treatment of the liver with a "preconditioning" protocol before its removal from the donor will help reduce any of this injury.

The "preconditioning" treatment being tested has two components. Firstly, a solution of glucose+insulin is infused and secondly, blood flow to the liver is stopped briefly (10 minutes) and then resumed. Both strategies, individually, have been shown to reduce liver tissue injury in human studies.

We hypothesize that combining both strategies will have a clinical benefit to patients and will improve liver function following transplant.


Condition or disease Intervention/treatment Phase
Liver Transplantation Procedure: Glucose/Ischemic Preconditioning Pre-treatment Phase 3

Detailed Description:
Liver transplantation is the only chance of cure for patients with end-stage liver disease. Unfortunately, standard organ preservation results in an ischemic-reperfusion injury (IRI) at the time of graft implantation. Novel strategies have been proposed to decrease reperfusion injury and improve graft function. This study will be the first to combine both strategies in a randomized, prospective trial. The intervention will occur during the retrieval surgery prior to cold preservation. Briefly, a glucose and insulin solution will be infused via the mesenteric vein at a controlled rate. Immediately prior to cross-clamping, blood supply to the liver will be restricted for 10 minutes and then resumed for 10 minutes before beginning cold preservation. All remaining surgical procedures, including the recipient surgery, will be performed by standard techniques. The liver recipient does not directly receive any intervention during this study.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized Trial to Investigate the Effects of Glucose/ Ischemic Preconditioning Donor Pre-treatment on Reperfusion Injury in Deceased-Donor Liver Transplantation
Study Start Date : August 2008
Primary Completion Date : June 2010
Study Completion Date : March 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Dextrose
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 1
Deceased liver donors that are randomized to this arm will receive the Glucose/Ischemic Preconditioning pre-treatment intra-operatively prior to starting cold preservation of the organ
Procedure: Glucose/Ischemic Preconditioning Pre-treatment
A 20% dextrose+insulin infusion is administered to the liver via the mesenteric vein beginning after cannulation of the mesenteric vein and ending immediately prior to flushing with cold preservation fluid. Also, after completion of the visceral dissection but prior to cross-clamping, ischemic precondition will occur. This involves occluding the portal vein and hepatic artery to stop blood flow for 10 minutes, then restoring blood flow for 10 minutes.
No Intervention: 2
Neither donors nor recipients receive any intervention. All procedures will be performed according to our institution's standard of care.


Outcome Measures

Primary Outcome Measures :
  1. Reperfusion injury determined by peak AST [ Time Frame: first 24 hours post-operative ]

Secondary Outcome Measures :
  1. Biliary Complications, infection and rejection [ Time Frame: first month post-transplantation ]
  2. graft and patient survival; length of hospital stay; length of ICU stay [ Time Frame: 30 days and 90 days post-transplantation ]
  3. Liver ATP and glycogen content; blood cytokine levels; liver gene expression of pro- and anti-apoptotic genes [ Time Frame: immediately pre-removal and post- transplantation ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recipient 18 years of age or older
  • Recipient with chronic end-stage liver disease
  • Deceased donor liver transplant
  • Recipient capable of providing written informed consent
  • Whole organ graft from donors aged 60 years or older

Exclusion Criteria:

  • Fulminant liver failure
  • Objection by any other member of the retrieval team
  • Split-liver grafts
  • Donor that has received total parenteral nutrition within 24hr of organ retrieval Donors from whom the pancreas and/or small bowel are also being retrieved
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00718575


Locations
Canada, Ontario
University Health Network (Toronto General Hospital)
Toronto, Ontario, Canada, M5G 2N2
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Markus Selzner, M.D. University Health Network, Toronto
More Information

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00718575     History of Changes
Other Study ID Numbers: 07-0587-AE
First Posted: July 18, 2008    Key Record Dates
Last Update Posted: July 25, 2014
Last Verified: June 2012

Keywords provided by University Health Network, Toronto:
Liver Disease
Transplantation

Additional relevant MeSH terms:
Reperfusion Injury
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Pathologic Processes