Evaluate Safety and Efficacy of Autologous Bone Marrow-derived Endothelial Progenitor Cells in Advanced Liver Cirrhosis

Study Overview
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Brief Summary
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Endothelial Progenitor Cells (EPC) represent a small cellular population of bone marrow and peripheral blood cells. EPCs are recruited into injured tissues and play an important role in regeneration and reparation. Experimental and clinical data suggest that EPCs have hepatoprotective activity and could improve liver regeneration during acute and chronic liver injury. The aim of this project is to evaluate the safety and therapeutic effects of autologous bone marrow-derived EPCs, when administered through the hepatic artery of patients with advanced liver cirrhosis.

Official Title
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Pilot Clinical Trial (Phase I/II) to Evaluate Safety and Therapeutic Effects of the Administration of Autologous Bone Marrow-derived EPCs in Patients With Advanced Liver Cirrhosis

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Other: Autologous bone marrow-derived endothelial progenitor cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver cirrhosis (Child-Pugh 8 or above). Ability to sign informed consent Exclusion Criteria: Age <18 or >75 Variceal bleeding or severe infection within the past 30 days before screening Chronic encephalopathy preventing the ability to sign informed consent (it could be done by legal representant of the patient) and/or the ability to follow the study protocol Hepatocellular carcinoma (previous or current) Any current or previous malignancy (within 5 years before the inclusion) except in situ tumors or skin basal cell carcinomas Any severe extrahepatic disease during the past 30 days before the inclusion Any current decompensated chronic disease Any contraindication for the examinations of the clinical protocol (medullar aspiration, arteriography, HVPG measurement) Any other condition that could negatively affect the compliance with the protocol Pregnant or breast-feeding women Participation in a trial of an experimental drug or device within 30 days before screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endothelial Progenitors Cells<br>Autologous bone marrow-derived endothelial progenitor cells | Other: Autologous bone marrow-derived endothelial progenitor cells<br>* Intraarterial administration (hepatic artery) of autologous bone marrow-derived endothelial progenitor cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and tolerability | The safety of the administration of autologous bone marrow-derived EPC in patients with advanced cirrhosis will be evaluated by anamnesis, physical examination, hematological and biochemical variables and imaging examination. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of liver function test as a measure of the effect on liver function | Determination of liver function test (aminotransferases,albumin, bilirubin and protrombin time) and calculation of Model for End-Stage Liver Disease (MELD) and Chil-Pugh scores. Differences in these variables compared to baseline will be considered as a measure of the effect on liver function. | 12 months | 
| Effect on portal hypertension | Changes in Hepatic Venous Pressure Gradient (HVPG) will be used to assess the effect on portal hypertension. | 12 months | 
| Effect on complications of liver cirrhosis | Ascitis grade, episodes of upper gastrointestinal bleeding as well as of episodes of hepatic encephalopathy will be used as a measure of the effect of the treatment on the complications of liver cirrhosis. | 12 months |