Safety Study of Autologous Stem Cell in Liver Cirrhosis

Study Overview
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Brief Summary
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It is a fase I/II clinical study to evaluate feasibility, safety and kinetics of cellular therapy with bone marrow-derived mononuclear cells (ABMMC) in patients with liver cirrhosis. All the patients have moderate liver disfunction and a waiting time expectancy of liver transplantation longer than 12 months due their low MELD score. The ABMMC are labeled with 99mTc and infused through the hepatic artery. Scintigraphy is performed 2 and 24 hours after infusion. Patients are submitted to frequent clinical, laboratorial and image evaluation during the follow up period of 12 months.

Detailed Description
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A one year clinical trial was conducted. Patients had moderate liver dysfunction and a liver transplant was not expected to occur earlier than 12 months, due to low MELD scores. Hepatocellular carcinoma (HCC) and hepatic artery or portal vein thrombosis were excluded by color Doppler ultrasonography (DUS) and 3-phase computed tomography (CT). Under local anesthesia, 100 mL of bone marrow were aspirated from the posterior iliac crest. ABMMC were isolated by density gradient centrifugation in Ficoll-Hypaque gradient, 10% of the cells were labeled with SnCl2-99mTc, and a small fraction was used for cell counting and viability analysis. ABMMC were delivered preferentially in the common hepatic artery by celiac trunk catheterism. Total body scintigraphy (TBS) was performed 3 hours after infusion. Patients were submitted to frequent clinical, biochemical and imaging evaluation during follow up.

Official Title
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Phase 1/2 Study of Autologous Bone Marrow Derived Mononuclear Cells in Liver Cirrhosis

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Procedure: Autologous bone marrow-derived mononuclear cells infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver cirrhosis of any origin Moderate liver disfunction (Child-Pugh Score=7-10) Exclusion Criteria: Waiting time expectancy of liver transplant shorter than 12 months Ongoing hepatic encephalopathy Clinically detectable ascitis Severe coagulation disorder (INR>2,0 or platelets count < 40.000) Diagnosis or strong suspicion of cancer (except basocellular) Pregnancy or intention to become pregnant during the next 12 months Moderate or severe co-morbidity Current participation in another clinical trial

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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Autologous bone marrow-derived mononuclear cells infusion|Under local anesthesia, 100 mL of bone marrow were aspirated from the posterior iliac crest. ABMMC were isolated by density gradient centrifugation in Ficoll-Hypaque gradient, 10% of the cells were labeled with SnCl2-99mTc, and a small fraction was used for cell counting and viability analysis. At least 100 millions of mononuclear-enriched BMC suspended in 20 mL of saline were delivered preferentially in the common hepatic artery by celiac trunk catheterism.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in liver function according to Child-Pugh and MELD scores |  | in days 1,2,7,14,30, 45, 60, 90, 120, 150, 180, 270, 360 | 
| Hepatic artery and portal vein thrombosis (doppler ultrasound) |  | in days 1,2,7,14,90, 180 and 360 | 
| Development of liver nodule (ultrasound screening) |  | in days 1,2,7,14,90, 180 and 360 (US) and in day 360 (CT scan ) | 
| Liver related mortality |  | 360 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body distribution of 99mTc labeled BMDMC (scintigraphy) |  | after 3 hours of infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cell, Liver cirrhosis, Cellular therapy, Autologous, Bone marrow