Hepatocyte Transplantation for Acute Decompensated Liver Failure

NCT01345565 | Withdrawn Phase 1 DMC

• 1 other identifier: PRO09020051
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Failure Acute

Keywords

fulminant hepatic failure

Outcome Measures

Primary Outcomes (1)

• Improvement in evidence of liver function at two weeks after hepatocyte transplant

  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.

  Two weeks after hepatocyte transplant

Secondary Outcomes (2)

• Immune Response

  two weeks after hepatocyte transplant and monthly thereafter post hepatocyte transplant

• Quality and Quantity of Hepatocytes

  Two weeks after hepatocyte transplant

Study Arms (1)

Hepatocyte Transplantation

EXPERIMENTAL

See Below

Drug: human hepatocytes

Interventions

human hepatocytes DRUG

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.

Hepatocyte Transplantation

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Ira Fox: lead

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15201, United States

Location

Related Publications (4)

• 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.

  PMID: 9580649 BACKGROUND

• 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.

  PMID: 9671059 BACKGROUND

• 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.

  PMID: 7940741 BACKGROUND

• 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.

  PMID: 2066062 BACKGROUND

MeSH Terms

Conditions

Liver Failure, Acute

Interventions

NOS2 protein, human

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Ira J Fox, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: April 26, 2011
• First Posted: May 2, 2011
• Study Start: March 1, 2011
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: January 23, 2019

Record last verified: 2019-01

Locations

US (1)