Dose Finding Study to Assess Safety and Efficacy of Stem Cells in Liver Cirrhosis

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of mesenchymal stem cells in patients with cirrhosis of liver. Stem cells will be injected into the hepatic artery. Improvement in various parameters will be observed over 2 years.

Official Title
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A Parallel Group Randomized Open Blinded End Point Evaluation, Multicentric, Dose Escalation, Phase -II Study Assessing the Safety and Efficacy of Intraarterial (Hepatic) Ex-vivo Cultured Adult Allogenic Mesenchymal Stem Cells in Patients With Alcoholic Liver Cirrhosis

Conditions
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Alcoholic Liver Cirrhosis

Intervention / Treatment
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* Biological: Allogeneic Mesenchymal Stem Cells
* Biological: Allogeneic Mesenchymal Stem Cells
* Biological: Allogeneic Mesenchymal Stem Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Alcoholic cirrhotics between 18-65 years of age (diagnosed by clinical, biochemical, sonographic, radiological [CT scan] or histological evidence of cirrhosis and portal hypertension). Evidence of decompensated liver disease at screening (e.g. Child class B or C, Child-Pugh scores of ≥7 and <14). MELD scores of at least 10 (UNOS Meld calculator). Normal AFP Level Hb>10gm/dl. Female patients of childbearing age must be willing to use accepted methods of contraception during the course of the study Signed informed consent. Exclusion Criteria: Patients likely to undergo liver transplantation during the duration of the study. Presence of advanced hepatic encephalopathy Grades 3 & 4 (West Haven criteria for grading of hepatic encephalopathy) at the time of screening Active variceal bleed. Refractory ascites. Evidences of autoimmune liver disease- ANA or Anti-LKM positivity. Platelet count < 30,000/mm3. Serum Sodium <129mEq/L. Serum Creatinine > 2 mg/dl. Hepatocellular carcinoma or other malignancies Active infectious disease. Presence of severe underlying cardiac, pulmonary or renal disease. Excessive alcohol (>30 gm of alcohol/day) use in the last 3 months before screening. Positive HbSAg or antibodies to HIV or HCV. Pregnancy or lactation. Participation in other clinical trials. Unwilling/unable to sign the informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>This arm will receive standard protocol of care alone | |
| Experimental: Stem cells high dose<br>This arm will receive high dose of Allogeneic Mesenchymal Stem Cells | Biological: Allogeneic Mesenchymal Stem Cells<br>* High dose of Bone Marrow Derived Allogeneic Mesenchymal Stem Cells will be administered through the hepatic artery<br>|
| Experimental: Stem cells intermediate dose<br>This arm will receive intermediate dose of Allogeneic Mesenchymal Stem Cells | Biological: Allogeneic Mesenchymal Stem Cells<br>* Intermediate dose of Bone Marrow Derived Allogeneic Mesenchymal Stem Cells will be administered through the hepatic artery<br>|
| Experimental: Stem cells low dose<br>This arm will receive low dose of Allogeneic Mesenchymal Stem Cells | Biological: Allogeneic Mesenchymal Stem Cells<br>* Low dose of Bone Marrow Derived Allogeneic Mesenchymal Stem Cells will be administered through the hepatic artery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | The type of adverse events, number of adverse events and proportion of patients with adverse events | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver function tests. | To assess the improvement in liver function | 2 years | 
| CT scan of abdomen. | To assess the improvement in liver structure | 2 years | 
| Change in MELD score | To assess the clinical improvement | 2 years | 
| Improvement in quality of life as assessed by SF 36 questionnaire | To assess the improvement in quality of life | 2 years | 
| Histological evaluation of liver biopsy by immunohistochemical staining for AFP, PCNA, SMA | To assess the improvement in histopathology | 6 Months | 
| Change in Child-Pugh score | To assess clinical improvement | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcoholic, Liver, Cirrhosis, Stem, Cells