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

This study has been terminated.
(too few patients meeting current eligibility criteria)
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00718575
First received: July 16, 2008
Last updated: July 24, 2014
Last verified: June 2012
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
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

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Reperfusion injury determined by peak AST [ Time Frame: first 24 hours post-operative ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Biliary Complications, infection and rejection [ Time Frame: first month post-transplantation ] [ Designated as safety issue: Yes ]
  • graft and patient survival; length of hospital stay; length of ICU stay [ Time Frame: 30 days and 90 days post-transplantation ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: August 2008
Study Completion Date: March 2012
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
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: 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

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00718575     History of Changes
Other Study ID Numbers: 07-0587-AE
Study First Received: July 16, 2008
Last Updated: July 24, 2014
Health Authority: Canada: Health Canada

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

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

ClinicalTrials.gov processed this record on October 21, 2014