Liver CirrhosisPhase 1/2hFLCTxNCT01013194
Human Fetal Liver Cell Transplantation in Chronic Liver Failure
A Phase 1/2 study testing Human Fetal Liver Cell Transplantation in people with Liver Cirrhosis, run by The Mediterranean Institute for Transplantation and Advanced Specialized Therapies at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Cirrhosis
- What is being tested?
- Human Fetal Liver Cell Transplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2007to Jul 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Conditions
- Liver Cirrhosis
- Being tested
- Human Fetal Liver Cell Transplantation
- Keywords
- Liver cirrhosis, Fetal stem cells, Stem cell transplantation, Liver transplant candidate
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human Fetal Liver Cell TransplantationOther
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 group | Role | What they receive |
|---|---|---|
| Treated patients | Experimental | Cirrhotic patients treated with Human Fetal Liver Cell Transplantation. Receives: Other: Human Fetal Liver Cell Transplantation |
| Control patients | No intervention | Cirrhotic patients on Standard therapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient Survival
Assessment of treated and control patients survival at 1 year follow-up
Measured: 1 year
Secondary outcomes (2)
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.
Measured: Baseline and 1 year Follow-up
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.
Measured: Baseline and 1 year Follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2009 (estimated)
- Study startFeb 2007
- Primary completionApr 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pittsburgh
- Responsible party
- Sponsor
- Investigators
- Bruno Gridelli, MD, Principal investigator, ISMETT-UPMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01013194
- Sponsor's protocol ID
- IRRB/01/06
- Acronym
- hFLCTx
- Status last verified
- Oct 2015
- First submitted
- 11 Nov 2009
- Last updated
- 3 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Failure
- ClinicalTrials.gov ID
- NCT01013194
- Acronym / sponsor ID
- hFLCTx / IRRB/01/06
- Conditions
- Liver Cirrhosis
- Keywords
- Liver cirrhosis, Fetal stem cells, Stem cell transplantation, Liver transplant candidate
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- The Mediterranean Institute for Transplantation and Advanced Specialized TherapiesUniversity, hospital or other
- Collaborators
- University of Pittsburgh
- Study start
- Feb 2007
- Primary completion
- Apr 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 13 Nov 2009 (estimated)
- Results
- Posted 3 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treated patients | Experimental | Other: Human Fetal Liver Cell TransplantationCirrhotic patients treated with Human Fetal Liver Cell Transplantation. |
| Control patients | No intervention | –Cirrhotic patients on Standard therapy. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (23 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Human Fetal Liver Cell TransplantationHuman 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. | Other | Treated patients |
Primary outcome
Patient Survival
Time frame: 1 year
Assessment of treated and control patients survival at 1 year follow-up
2 secondary outcomes
Analysis of Child-Pugh Score From Baseline to 1 Year Follow-up
Time frame: Baseline and 1 year Follow-up
Analysis of Meld Score From Baseline to 1 Year Follow-up
Time frame: Baseline and 1 year Follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruno Gridelli, MD principal investigator
ISMETT-UPMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Human Fetal Liver Cell Transplantation in people with Liver Cirrhosis, run by The Mediterranean Institute for Transplantation and Advanced Specialized Therapies at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient Survival (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2015.