Clinical trial NCT01345565: Hepatocyte Transplantation for Acute Decompensated Liver Failure
Official title: Hepatocyte Transplantation for Acute Decompensated Liver Failure
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Liver Failure Acute
Keywords: fulminant hepatic failure
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2011-05-02
Enrollment: 0
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Improvement in evidence of liver function at two weeks after hepatocyte transplant
timeFrame: Two weeks after hepatocyte transplant
Secondary outcomes:
measure: Immune Response
timeFrame: two weeks after hepatocyte transplant and monthly thereafter post hepatocyte transplant
measure: Quality and Quantity of Hepatocytes
timeFrame: Two weeks after hepatocyte transplant
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Ira J Fox, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI, Dorko K, Sauter BV, Strom SC. Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med. 1998 May 14;338(20):1422-6. doi: 10.1056/NEJM199805143382004. No abstract available.
citation: Roger V, Balladur P, Honiger J, Baudrimont M, Delelo R, Robert A, Calmus Y, Capeau J, Nordlinger B. Internal bioartificial liver with xenogeneic hepatocytes prevents death from acute liver failure: an experimental study. Ann Surg. 1998 Jul;228(1):1-7. doi: 10.1097/00000658-199807000-00001.
citation: Habibullah CM, Syed IH, Qamar A, Taher-Uz Z. Human fetal hepatocyte transplantation in patients with fulminant hepatic failure. Transplantation. 1994 Oct 27;58(8):951-2. doi: 10.1097/00007890-199410270-00016. No abstract available.
citation: Gupta S, Aragona E, Vemuru RP, Bhargava KK, Burk RD, Chowdhury JR. Permanent engraftment and function of hepatocytes delivered to the liver: implications for gene therapy and liver repopulation. Hepatology. 1991 Jul;14(1):144-9. doi: 10.1002/hep.1840140124.