Clinical trial NCT01013194: Human Fetal Liver Cell Transplantation in Chronic Liver Failure
Official title: Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Liver Cirrhosis
Keywords: Liver cirrhosis
Fetal stem cells
Stem cell transplantation
Liver transplant candidate
Lead sponsor: The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
First posted: 2009-11-13
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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).

Primary outcomes:
measure: Patient Survival
timeFrame: 1 year
Secondary outcomes:
measure: Analysis of Child-Pugh Score From Baseline to 1 Year Follow-up
timeFrame: Baseline and 1 year Follow-up
measure: Analysis of Meld Score From Baseline to 1 Year Follow-up
timeFrame: Baseline and 1 year Follow-up
Other outcomes:
Locations:
city: Palermo
country: Italy
facility: ISMETT
Study officials:
affiliation: ISMETT-UPMC
name: Bruno Gridelli, MD
role: PRINCIPAL_INVESTIGATOR
References: