Human Fetal Liver Cell Transplantation in Chronic Liver Failure

NCT ID: NCT01013194

Last Updated: 2015-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2011-07-31

Brief Summary

The herein study consists in the transplantation of liver progenitor cells isolated from human fetal liver tissue with the aim of improving conventional liver therapy and broadening therapeutical options other than liver transplantation.

Detailed Description

One of the major clinical problems in transplantation medicine is the discrepancy between the growing number of liver chronic disease patients and the lack of organs. Research and development of new liver failure treatments thus have a high clinical significance. Regenerative medicine and results recently achieved in the field of stem cell biology may provide a remedy to this emerging problem.

Our project aims at developing new generation cell transplantation methodologies through an interdisciplinary research project created from a collaboration between ISMETT, Palermo and the University of Pittsburgh (UPMC-USA).

Adult hepatocyte transplantation has been in use for several years already and has proved to be safe for patients and able, especially in pediatric patients, to improve liver function indices and delay the need for liver transplantation. Studies have been limited until now by the use of already differentiated hepatocytes and therefore unable to proliferate and develop a suitable liver mass to support a decompensated liver.

The hypothesis of our project, supported by in vitro studies and studies on experimental animal models, is based on the possibility to generate an ectopic liver system in the spleen through the experimental use of hepatic cell progenitors obtained from human fetal liver tissues. Human fetal liver cell transplantation will be performed in the spleen through arterial injection.

The final endpoint of the project is to develop an innovative and safe treatment for patients with end-stage chronic liver failure

Conditions

Liver Cirrhosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treated patients

Cirrhotic patients treated with Human Fetal Liver Cell Transplantation.

Group Type: EXPERIMENTAL

Human Fetal Liver Cell Transplantation

Intervention Type: OTHER

Human Fetal Liver Cell Transplantation. Cell source: Non-purified and non-selected fetal liver cells from fetuses aborted between the 16th and 26th week of gestation.

Infusion technique: Isolation and incannulation of the femoral artery.Splenic artery infusion under radiological guidance.

Cell infusion: between 5 and 10x10^8 cells. Number of sessions: up to 2.

Control patients

Cirrhotic patients on Standard therapy.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Human Fetal Liver Cell Transplantation

Human Fetal Liver Cell Transplantation. Cell source: Non-purified and non-selected fetal liver cells from fetuses aborted between the 16th and 26th week of gestation.

Infusion technique: Isolation and incannulation of the femoral artery.Splenic artery infusion under radiological guidance.

Cell infusion: between 5 and 10x10^8 cells. Number of sessions: up to 2.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis (evidence of chronic liver disease, presence of ascites and/or esophageal varices upon superior digestive endoscopy and/or ultrasound evidence of portal hypertension) or histological diagnosis of liver cirrhosis with any etiology.
• Serious liver failure documented by a score ≥ B8 based on the Child-Pugh-Turcotte classification and/or MELD score ≥ 14.
• Informed consent to the study signed by the patient.

Exclusion Criteria

• MELD score ≥ 25
• Hepatocellular carcinoma (HCC)
• Portal vein thrombosis
• Serious cardiovascular or respiratory disease, or other medical condition which may threaten patient's life in the subsequent three months
• Admission to the Intensive Care Unit (ICU)
• Hemodynamic instability (MAP < 55 mmHg)
• Use of vasoactive drugs (Epinephrine, Norepinephrine, Vasopressin, Dopamine, Terlipressine
• Type-1 (acute) hepatorenal syndrome
• Levels of serum creatinine >2 mg/dl and/or creatinine clearance <30-40 ml/min
• Sepsis, active infection or spontaneous bacterial peritonitis
• Active gastrointestinal bleeding or recent gastrointestinal bleeding episode (in the previous 4 weeks)
• Active alcohol abuse
• Severe alcoholic hepatitis
• Pulmonary hypertension (PAP > 35 mmHg)
• History of neoplasia
• Pregnancy
• Non Sicilian residency
• HBV DNA positive
• HIV infection
• Drug addiction
• Age < 18 years
• Transjugular intrahepatic portosystemic shunt (TIPS) placed in the previous month
• Contraindications to the procedure (e.g., related to the splenic artery: aneurysm, kinking, thrombosis, splenic-renal shunt; related to the spleen: large angioma).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

The Mediterranean Institute for Transplantation and Advanced Specialized Therapies

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruno Gridelli, MD

Role: PRINCIPAL_INVESTIGATOR

ISMETT-UPMC

Locations

ISMETT

Palermo, , Italy

Countries

Italy

Other Identifiers

IRRB/01/06

Identifier Type: -

Identifier Source: org_study_id