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Human Fetal Liver Cell Transplantation in Chronic Liver Failure

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2009 by The Mediterranean Institute for Transplantation and Advanced Specialized Therapies.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
University of Pittsburgh
UP
Information provided by:
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
ClinicalTrials.gov Identifier:
NCT01013194
First received: November 11, 2009
Last updated: November 12, 2009
Last verified: November 2009
  Purpose

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.


Condition Intervention Phase
Liver Cirrhosis
Other: Human Fetal Liver Cell Transplantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Failure - Transplant Experimentation

Resource links provided by NLM:


Further study details as provided by The Mediterranean Institute for Transplantation and Advanced Specialized Therapies:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 30
Study Start Date: February 2007
Estimated Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Human Fetal Liver Cell Transplantation 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 1x108 and 5x108 cells during each session. Number of sessions: up to 4 sessions.


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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (Appendix 1) 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01013194

Locations
Italy
ISMETT Recruiting
Palermo, Italy, 90120
Contact: Bruno Gridelli, MD    0039.091.21.92.442    ddonato@ismett.edu   
Contact: Giada Pietrosi, MD    0039.091.21.92.601    gpietrosi@ismett.edu   
Principal Investigator: Bruno Gridelli, MD         
Sponsors and Collaborators
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
University of Pittsburgh
UP
  More Information

No publications provided

Responsible Party: Bruno Gridelli, ISMETT
ClinicalTrials.gov Identifier: NCT01013194     History of Changes
Other Study ID Numbers: IRRB/01/06
Study First Received: November 11, 2009
Last Updated: November 12, 2009
Health Authority: Italy: Ethics Committee

Keywords provided by The Mediterranean Institute for Transplantation and Advanced Specialized Therapies:
Liver cirrhosis
Fetal stem cells
Stem cell transplantation
Liver transplant candidates

Additional relevant MeSH terms:
End Stage Liver Disease
Liver Cirrhosis
Liver Failure
Digestive System Diseases
Hepatic Insufficiency
Liver Diseases
Liver Extracts
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014