Ischemic Preconditioning of Liver in Cadaver Donors

NCT00245830 | Completed

• 1 other identifier: 0120010348
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The long-term goals of this proposal are to develop clinical protocols of donor preconditioning to improve liver graft function and ameliorate complications of poor graft function after liver transplantation. Achievement of these objectives would improve liver recipient outcomes, increase utilization of livers and alleviate the current critical shortage of livers for transplantation. More stringent liver donor selection intended to decrease the complications of poor graft function conflicts directly with efforts to maximize the use of donor livers. Ischemic preconditioning (IPC) of liver attenuates hepatic ischemia reperfusion injury (IRI) in animals. Preliminary data show hepatic IPC effectively decreases IRI following hepatic resection in humans. The specific aims of this project are: AIM 1: To test the hypothesis that 10 minutes of hepatic ischemic preconditioning in deceased donors would improve liver graft function and decrease injury in the early post transplant period. AIM 2: To test the hypothesis that ischemic preconditioning of deceased donor livers would decrease systemic inflammatory response in liver recipients in the early post transplant period. AIM 3: To examine whether ischemic preconditioning of deceased donor livers decreases early post transplant pulmonary edema and acute rejection and shortens hospital stay.

Conditions

Liver Cirrhosis; Liver Disease

Keywords

Ischemia/reperfusion of the liver; Ischemic Preconditioning; Cadaver organ donor

Outcome Measures

Primary Outcomes (1)

• Changes in INR/PT and serum AST, ALT and TB levels

  Values immediately post-transplantation and on days 1 - 3 and days 7, 14 and 30 post-transplantation

Secondary Outcomes (3)

• Plasma levels of cytokines

  Blood samples are collected at pre-incision of abdomen, cross-clamp of abdominal aorta; 3 hour postreprofusion and post-transplant day one in the recipient

• Interstitial and alveolar edema in chest radiographs

  days 1 - 3 post transplant

• Length of Hospital stay

  number of days from Liver transplant to hospital discharge on average 10 days

Study Arms (2)

No Hepatic Ischemic Preconditioning

NO INTERVENTION

donor will act as a sham control.

Hepatic Ischemic Preconditioning

EXPERIMENTAL

blood flow to the liver will be cut off by hilar clamping for ten minutes followed by release of the clamp prior to removal of the liver from the donor.

Procedure: Ischemic Preconditioning

Interventions

Ischemic Preconditioning PROCEDURE

Experimental: Hepatic Ischemic Preconditioning blood flow to the liver will be cut off by hilar clamping for ten minutes followed by release of the clamp prior to removal of the liver from the donor.

Hepatic Ischemic Preconditioning

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Deceased donor livers allocated to adult (\> 18 years of age) recipients at the research site.

You may not qualify if:

• Deceased donor livers allocated to recipients at centers other than the research site.
• Deceased donor livers allocated to recipients \< 18 years of age at the research site.
• Non-heart beating donors
• Deceased liver and small intestine donors
• Live liver donors.

Sponsors & Collaborators

• University of Medicine and Dentistry of New Jersey: lead

Study Sites (1)

University Hospital

Newark, New Jersey, 07101, United States

Location

Related Publications (4)

• Koneru B, Fisher A, He Y, Klein KM, Skurnick J, Wilson DJ, de la Torre AN, Merchant A, Arora R, Samanta AK. Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy. Liver Transpl. 2005 Feb;11(2):196-202. doi: 10.1002/lt.20315.

  PMID: 15666380 BACKGROUND

• Raza A, Dikdan G, Desai KK, Shareef A, Fernandes H, Aris V, de la Torre AN, Wilson D, Fisher A, Soteropoulos P, Koneru B. Global gene expression profiles of ischemic preconditioning in deceased donor liver transplantation. Liver Transpl. 2010 May;16(5):588-99. doi: 10.1002/lt.22049.

  PMID: 20440768 BACKGROUND

• Desai KK, Dikdan GS, Shareef A, Koneru B. Ischemic preconditioning of the liver: a few perspectives from the bench to bedside translation. Liver Transpl. 2008 Nov;14(11):1569-77. doi: 10.1002/lt.21630.

  PMID: 18975290 BACKGROUND

• Koneru B, Shareef A, Dikdan G, Desai K, Klein KM, Peng B, Wachsberg RH, de la Torre AN, Debroy M, Fisher A, Wilson DJ, Samanta AK. The ischemic preconditioning paradox in deceased donor liver transplantation-evidence from a prospective randomized single blind clinical trial. Am J Transplant. 2007 Dec;7(12):2788-96. doi: 10.1111/j.1600-6143.2007.02009.x. Epub 2007 Oct 19.

  PMID: 17949458 RESULT

MeSH Terms

Conditions

Liver Cirrhosis; Liver Diseases; Ischemia

Interventions

Ischemic Preconditioning

Condition Hierarchy (Ancestors)

Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Investigative Techniques

Study Officials

• Baburao Koneru, M.D.

  UMDNJ-New Jersey Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2005
• First Posted: October 28, 2005
• Study Start: October 1, 2003
• Primary Completion: July 1, 2006
• Study Completion: March 1, 2007
• Last Updated: January 19, 2015

Record last verified: 2015-01

Locations

US (1)