Autologous Bone Marrow Stem Cells in Cirrhosis Patients

Autologous Transplantation of Bone Marrow Derived CD 133 Positive Stem Cell and Mono Nuclear Cell (MNC) Transplantation in Patients With Decompensate Cirrhosis: Randomized Clinical Trial

Liver cirrhosis (LC) is the end stage of chronic liver disease. The liver transplantation is one of the only effective therapies available to such patients. However, lack of donors, surgical complications, rejection, and high cost are it's serious problems. The potential for stem cells in bone marrow (BM) to differentiate into hepatocytes cells was recently confirmed. Moreover, BMC transplantation has been performed to treat hematological diseases, and several clinical studies have applied BMC injection to induce regeneration of myocardium and blood vessels. In this study we will evaluate safety and feasibility of autologous bone marrow mono nuclear (BM-MNC) and enriched CD133+ hematopoietic stem cell transplantation through the portal vein in patients with decompensate cirrhosis.

Study Overview

• Status: Completed
• Conditions: Stem Cell Transplantation; Cirrhosis
• Intervention / Treatment: Biological: CD133; Biological: BM-MNC

Detailed Description

BM (200 ml) will be harvested from the iliac crest according to standard procedures under general anesthesia and is collected in plastic bags containing anti coagulant. After precipitation of red blood cells, Low density mononuclear cells will be collected by centrifugation in Ficoll-Paque density gradient. For CD133+ cells separation the CliniMACS instrument will be used. Cells are injected via portal vein under sonography monitoring. After cell therapy, patients are followed up every week for 4 weeks, and laboratory data are analyzed for 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1665659911
    • Royan Institute
  • Fars
    • Shiraz, Fars, Iran, Islamic Republic of
      • Liver Transplant Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Liver biopsy showing histological Cirrhosis, grade B or C (Child-Pugh score)
• Alkaline phosphatase between 2 X to 3X normal value
• liver Cirrhosis in Sonography study
• Incomplete response to UDCA after 6 months of treatment.
• Negative pregnancy test (female patients in fertile age)
• written consent

Exclusion Criteria:

• Presence of active hepatic encephalopathy
• Refractory ascites
• Evidences of active autoimmune liver disease (e.g. gamma globulin of more than 2 times of upper limit of normal, and ALT > 3 times normal in patients with autoimmune hepatitis)
• Hepatocellular carcinoma or other malignancies
• sepsis
• Presence of significant extrahepatic biliary disease (e.g. CBD stone, PSC, etc.)
• HIV, HBV or HCV infection
• Cardiac, renal or respiratory failure
• Active thrombosis of the portal or hepatic veins
• INR>2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Biological: CD133; portal vein infusion of CD133+ cells
Experimental: 2	Biological: BM-MNC; portal vein infusion of BM-MNC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Liver function test	6 months
MELD score	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Cirrhosis mortality	6 months

Collaborators and Investigators

• Sponsor: Royan Institute
• Collaborators: Shiraz University of Medical Sciences; Small Business Developing Center
• Investigators: Study Chair: Hamid Gorabi, PhD, Royan Institute, Tehran, Iran; Principal Investigator: Hossein Baharvand, PhD, Royan Institute, Tehran, Iran; Study Chair: Malekhosseini, MD, Liver Transplantation Research Center, Shiraz, Iran; Principal Investigator: Saman Nikeghbal, MD, Liver Transplantation Research Center, Shiraz, Iran; Study Director: Nasser Aghdami, MD, PhD, Royan Institute, Tehran, Iran

Publications and helpful links

General Publications

• Nikeghbalian S, Pournasr B, Aghdami N, Rasekhi A, Geramizadeh B, Hosseini Asl SM, Ramzi M, Kakaei F, Namiri M, Malekzadeh R, Vosough Dizaj A, Malek-Hosseini SA, Baharvand H. Autologous transplantation of bone marrow-derived mononuclear and CD133(+) cells in patients with decompensated cirrhosis. Arch Iran Med. 2011 Jan;14(1):12-7.

Helpful Links

• Royan Institute
• Shiraz University Of Medical Sciences, Transplantation Research center

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: July 9, 2008
• First Submitted That Met QC Criteria: July 11, 2008
• First Posted (Estimate): July 14, 2008

Study Record Updates

• Last Update Posted (Estimate): October 4, 2011
• Last Update Submitted That Met QC Criteria: October 1, 2011
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Cirrhosis; Autologous Bone marrow stem cells
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: Liver-001