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

• ClinicalTrials.gov Identifier: NCT01013194
• Recruitment Status: Completed
• First Posted: November 13, 2009
• Results First Posted: November 3, 2015
• Last Update Posted: November 3, 2015
• Sponsor: The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
• Collaborator: University of Pittsburgh
• Information provided by (Responsible Party): The Mediterranean Institute for Transplantation and Advanced Specialized Therapies

Tracking Information

• First Submitted Date: November 11, 2009
• First Posted Date: November 13, 2009
• Results First Submitted Date: October 29, 2014
• Results First Posted Date: November 3, 2015
• Last Update Posted Date: November 3, 2015
• Study Start Date: February 2007
• Actual Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2015)

Patient Survival [ Time Frame: 1 year ]

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

• Original Primary Outcome Measures (submitted: November 12, 2009): 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 ]

Current Secondary Outcome Measures (submitted: October 2, 2015)

• Analysis of Child-Pugh Score From Baseline to 1 Year Follow-up [ Time Frame: Baseline and 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 [ Time Frame: Baseline and 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.

• Original Secondary Outcome Measures (submitted: November 12, 2009): 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 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Human Fetal Liver Cell Transplantation in Chronic Liver Failure
• Official Title: Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Failure
• 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

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Liver Cirrhosis

Intervention

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.

Study Arms

• 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.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 2, 2015): 25
• Original Estimated Enrollment (submitted: November 12, 2009): 30
• Actual Study Completion Date: July 2011
• Actual Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT01013194
• Other Study ID Numbers: IRRB/01/06
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
• Original Responsible Party: Bruno Gridelli, ISMETT
• Current Study Sponsor: The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
• Original Study Sponsor: Same as current
• Collaborators: University of Pittsburgh

Investigators

• Principal Investigator: Bruno Gridelli, MD; ISMETT-UPMC

• PRS Account: The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
• Verification Date: October 2015