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

Primary Purpose

Liver Cirrhosis

Status
Completed
Phase
Phase 1
Locations
Italy
Study Type
Interventional
Intervention
Human Fetal Liver Cell Transplantation
Sponsored by
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cirrhosis focused on measuring Liver cirrhosis, Fetal stem cells, Stem cell transplantation, Liver transplant candidate

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • ISMETT

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Treated patients

Control patients

Arm Description

Cirrhotic patients treated with Human Fetal Liver Cell Transplantation.

Cirrhotic patients on Standard therapy.

Outcomes

Primary Outcome Measures

Patient Survival
Assessment of treated and control patients survival at 1 year follow-up

Secondary Outcome Measures

Analysis of Child-Pugh Score From Baseline to 1 Year Follow-up
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
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.

Full Information

First Posted
November 11, 2009
Last Updated
October 2, 2015
Sponsor
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
Collaborators
University of Pittsburgh
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1. Study Identification

Unique Protocol Identification Number
NCT01013194
Brief Title
Human Fetal Liver Cell Transplantation in Chronic Liver Failure
Acronym
hFLCTx
Official Title
Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Failure
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
Collaborators
University of Pittsburgh

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis
Keywords
Liver cirrhosis, Fetal stem cells, Stem cell transplantation, Liver transplant candidate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treated patients
Arm Type
Experimental
Arm Description
Cirrhotic patients treated with Human Fetal Liver Cell Transplantation.
Arm Title
Control patients
Arm Type
No Intervention
Arm Description
Cirrhotic patients on Standard therapy.
Intervention Type
Other
Intervention Name(s)
Human Fetal Liver Cell Transplantation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Patient Survival
Description
Assessment of treated and control patients survival at 1 year follow-up
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Analysis of Child-Pugh Score From Baseline to 1 Year Follow-up
Description
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.
Time Frame
Baseline and 1 year Follow-up
Title
Analysis of Meld Score From Baseline to 1 Year Follow-up
Description
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.
Time Frame
Baseline and 1 year Follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno Gridelli, MD
Organizational Affiliation
ISMETT-UPMC
Official's Role
Principal Investigator
Facility Information:
Facility Name
ISMETT
City
Palermo
ZIP/Postal Code
90127
Country
Italy

12. IPD Sharing Statement

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Human Fetal Liver Cell Transplantation in Chronic Liver Failure

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