Hepatocyte Transplantation for Acute Decompensated Liver Failure

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01345565
First received: April 26, 2011
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

The purpose of this research study is to determine whether liver cell transplantation can provide help for patients with liver failure who are unlikely to survive without some form of liver support. The goal of this research study is to determine if liver cell transplants can be effective until a liver transplant is received or until patients recover from their liver failure.


Condition Intervention Phase
Liver Failure Acute
Drug: human hepatocytes
Phase 1

Study Type: Interventional
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

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 15
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)
Arms Assigned Interventions
Experimental: Hepatocyte Transplantation
See Below
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.


Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects will include those patients with ALF who are potential conventional liver transplant recipient candidates based on PELD criteria as well as those who would not be considered candidates for orthotopic liver transplantation (e.g. patients who appear to be too small or too ill for solid organ transplant or those who have a diagnosis that is a contradiction for whole organ transplantation, for example, systemic mitochondrial hepatopathy).
  • If the patient is a candidate for orthotopic liver transplantation (per standard clinical criteria), they will be officially listed for liver transplantation as well as hepatocyte transplantation.
  • If a subject is a potential conventional liver transplant recipient candidate and a donor liver is available; the patient will receive a solid organ transplant.
  • Subjects ages 0-21 years old will be included in this study.

Exclusion Criteria:

The patient has:

  1. Severe cardiovascular or respiratory disease at baseline and at the time of hepatocyte transplant as defined by

    1. Central venous pressure >25 mm Hg or if known, pulmonary capillary wedge pressure of >30 mg Hg or
    2. Oxygen saturation of <90% on > 60% oxygen OR a P/F ratio (Po2/FiO2) of <1.
  2. Hemodynamically significant gastrointestinal bleeding causing a systolic blood pressure <70mmHg at the time of transplantation.
  3. Uncorrectable coagulopathy despite use of plasmapheresis that would preclude any invasive procedures.
  4. Leukopenia at the time of cell transplant, defined as an absolute neutrophil count of <500/µL.
  5. Known allergy to immunosuppression medications that are required post transplant procedure for the prevention of rejection.
  6. Active malignancy except those with acute liver failure during treatment with estimated life expectancies of >1 year if the malignancy is controlled.
  7. Sepsis or other active infection except those without evidence of hemodynamically significant uncontrollable systemic sepsis with positive blood or tissue cultures.
  8. Intrauterine pregnancy. All females of childbearing potential will receive a pregnancy test prior to enrollment.
  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: NCT01345565

Contacts
Contact: Rachel E Sada, MS, CIP 412-692-7673 novoselre@upmc.edu
Contact: Maria Bond 412-692-7133 bondma@upmc.edu

Locations
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         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Ira J Fox, MD University of Pittsburgh