Hepatocyte Transplantation for Acute Decompensated Liver Failure
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Hepatocyte Transplantation for Acute Decompensated Liver Failure|
- Improvement in evidence of liver function at two weeks after hepatocyte transplant [ Time Frame: Two weeks after hepatocyte transplant ] [ Designated as safety issue: Yes ]The extent to which hepatocyte transplantation can elicit evidence of improvement in liver function in patients with acute decompensated liver failure not responding to medical management.
- Immune Response [ Time Frame: two weeks after hepatocyte transplant and monthly thereafter post hepatocyte transplant ] [ Designated as safety issue: Yes ]The extent to which the standard immune suppression medications used for solid organ transplantation can effectively control rejection and preserve the function of transplanted hepatocytes without leading to overwhelming infection or other medication related toxicities in the face of hepatic failure.
- Quality and Quantity of Hepatocytes [ Time Frame: Two weeks after hepatocyte transplant ] [ Designated as safety issue: Yes ]The relationship between number and quality of donor hepatocytes infused and engraftment in the livers of patients with the acute liver injury.
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||February 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: Hepatocyte Transplantation
Drug: human hepatocytes
The intrahepatic site for liver cell transplantation has been associated with the best engraftment and function based on animal experiments. Several approaches for access to the portal vein will be considered. The technique used will be determined based on what is considered best for the child based on risk/benefit at the time.
We propose to attempt to infuse approximately 5-10% of the hepatic mass in order to provide improved hepatic function. Since we do not yet know from our experience so far the correct number of cells to transplant in order to improve function, we will continue to infuse hepatocytes as donors become available until the patient improves to the point where they are no longer meet the criteria for organ transplantation. The subject will be evaluated de novo and if they are a candidate for orthotopic liver transplantation they will receive the transplant.
Orthotopic liver transplantation has become the treatment of choice for patients with acute liver failure with poor prognostic signs. Survival following hepatic transplantation has improved in the last decade for a number of reasons. These include improvement in immunosuppression, improved methods for preserving and transporting organs, use of donors which had been previously considered unacceptable, use of reduced-sized grafts , and the use of living-donor hepatic transplantation. Despite encouraging survival statistics, there continues to be significant morbidity and mortality associated with hepatic transplantation. In addition, the success of hepatic transplantation has broadened the indications for this form of therapy without a concomitant increase in the number of donors available for these patients.
Since the development of a method for isolating primary hepatocytes by collagenase perfusion, many investigators have demonstrated the efficacy of hepatocyte transplantation in the treatment of liver failure and inherited metabolic disorders in experimental animals. Treatment of liver diseases with transplantation of isolated hepatocytes rather than the whole liver has several theoretical advantages. Unlike the whole liver, isolated hepatocytes could be cryopreserved for instant availability and could be modified genetically or otherwise to enhance specific functions, stimulate proliferation or abrogate allograft rejection. Hepatocyte transplantation should be less stressful than whole liver transplantation because the host organ remains intact. Since the transplanted cells integrate into the host liver, they could provide restorative potential and the consequences of graft loss would be relatively minor. In addition, hepatocyte transplantation would not interfere with subsequent liver transplantation, should that become necessary.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01345565
|Contact: Rachel E Sada, MS, CIPfirstname.lastname@example.org|
|Contact: Maria Bondemail@example.com|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15201|
|Principal Investigator: Ira J Fox, MD|
|Sub-Investigator: Kyle Soltys, MD|
|Sub-Investigator: George Mazariegos, MD|
|Sub-Investigator: Rakesh Sindhi, MD|
|Sub-Investigator: Geoffrey Bond, MD|
|Sub-Investigator: John Crowley, MD|
|Sub-Investigator: Gerard Vockley, MD|
|Sub-Investigator: Georgianne Arnold, MD|
|Sub-Investigator: Robert Squires, MD|
|Sub-Investigator: Ben Shneider, MD|
|Sub-Investigator: Charles Fitz, MD|
|Principal Investigator:||Ira J Fox, MD||University of Pittsburgh|