Human Fetal Liver Cell Transplantation in Chronic Liver Failure (hFLCTx)

This study has been completed.
Sponsor:
Collaborator:
UPMC
Information provided by (Responsible Party):
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
ClinicalTrials.gov Identifier:
NCT01013194
First received: November 11, 2009
Last updated: October 2, 2015
Last verified: October 2015

November 11, 2009
October 2, 2015
February 2007
April 2011   (final data collection date for primary outcome measure)
Patient Survival [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Assessment of treated and control patients survival at 1 year follow-up
Assess the therapeutic efficacy of human fetal liver progenitor cell transplantation by monitoring standard and specific liver function parameters [ Time Frame: 6 months, 1 year ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01013194 on ClinicalTrials.gov Archive Site
  • Analysis of Child-Pugh Score From Baseline to 1 Year Follow-up [ Time Frame: Baseline and 1 year Follow-up ] [ Designated as safety issue: No ]

    Assessment of the efficacy of human fetal liver progenitor cell transplantation on Child-Pugh score.

    The Child-Pugh (CP) classification is a scoring system used for the classification of the severity of cirrhosis. It includes three continuous variables (bilirubin, albumin and INR) and two discrete variables (ascites and encephalopathy). Each variable is scored 1-3 with 3 indicating most severe derangement. The determination of CP score may range from 5 to 15 and the final score allows to categorize patients in Child-Pugh A (5-6 points), B (7-9 points) and C (10-15 points). The highest is the score the sickest is the patient.

  • Analysis of Meld Score From Baseline to 1 Year Follow-up [ Time Frame: Baseline and 1 year Follow-up ] [ Designated as safety issue: No ]

    Assessment of the efficacy of human fetal liver progenitor cell transplantation on Meld score.

    The Model for End-stage Liver Disease (MELD) scoring system aims at stratifying recipients by their disease severity according to a score estimating the 3-month probability of death on the waiting list. The calculation of an individual's MELD score is based on three objective lab parameters (bilirubin, serum creatinine and prothrombin time expressed as international normalized ratio, INR) and it includes logarithmic transformations and multiplication by several factors. It ranges between 6 and 40. The highest is the score the lower is the patient's survival.

Assess the safety of human fetal liver progenitor cell transplantation on the clinical course of chronic liver failure patients Assess the development of ectopic liver tissue in the spleen by means of serial imaging studies. [ Time Frame: 6 months, 1 year ] [ Designated as safety issue: Yes ]
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Human Fetal Liver Cell Transplantation in Chronic Liver Failure
Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Failure
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.

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

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Liver Cirrhosis
Other: 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.

  • Experimental: Treated patients
    Cirrhotic patients treated with Human Fetal Liver Cell Transplantation.
    Intervention: Other: Human Fetal Liver Cell Transplantation
  • No Intervention: Control patients
    Cirrhotic patients on Standard therapy.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
July 2011
April 2011   (final data collection date for primary outcome measure)

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).
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
NCT01013194
IRRB/01/06
Yes
Not Provided
Not Provided
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
UPMC
Principal Investigator: Bruno Gridelli, MD ISMETT-UPMC
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP