Clinical trial NCT00713934: Autologous Bone Marrow Stem Cells in Cirrhosis Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Stem Cell Transplantation
Cirrhosis
Keywords: Autologous Bone marrow stem cells
Cirrhosis
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
Collaborators: name: Small Business Developing Center
name: Shiraz University of Medical Sciences
First posted: 2008-07-14
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Liver function test
timeFrame: 6 months
measure: MELD score
timeFrame: 6 months
Secondary outcomes:
measure: Cirrhosis mortality
timeFrame: 6 months
Other outcomes:
Locations:
city: Shiraz
country: Iran, Islamic Republic of
facility: Liver Transplant Research Center
state: Fars
city: Tehran
country: Iran, Islamic Republic of
facility: Royan Institute
Study officials:
affiliation: Royan institute, Tehran, Iran
name: Hamid Gorabi, PhD
role: STUDY_CHAIR
affiliation: Liver Transplantation Research Center, Shiraz, Iran
name: Malekhosseini, MD
role: STUDY_CHAIR
affiliation: Royan institute, Tehran, Iran
name: Hossein Baharvand, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Liver Transplantation Research Center, Shiraz, Iran
name: Saman Nikeghbal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royan institute, Tehran, Iran
name: Nasser Aghdami, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.