Clinical trial NCT00476060: Mesenchymal Stem Cell Transplantation in Decompensated Cirrhosis
Official title: Autologous Mesenchymal Stem Cell Transplantation in Patients With Decompensated Cirrhosis: A Randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cirrhosis
Keywords: Cirrhosis
Bone marrow
Mesenchymal stem cell
MELD score
Quality of life
Lead sponsor: University of Tehran
Sponsor class: OTHER
First posted: 2007-05-21
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The standard treatment for decompensated cirrhosis is liver transplantation, however, it has several limitations. Recent animal studies suggest that bone marrow stem cell transplantation can lead to regression of liver fibrosis. The investigators have already completed the phase 1 study of bone marrow mesenchymal stem cell (MSC) transplantation in 4 patients with cirrhosis. The procedure was safe, and feasible, and led to somewhat promising results (Mohamadnejad M, et al. 2006; Submitted for publication). The aim of this study is to find efficacy of this new treatment strategy in the setting of a multicenter, randomized placebo-controlled trial in 50 patients with decompensated cirrhosis.

Detailed description: The standard treatment for decompensated cirrhosis is liver transplantation, however, it has several limitations, including small donor pool, long waiting list, and several complications. Recent animal studies suggest that bone marrow stem cell transplantation can lead to regression of liver fibrosis. The investigators have already completed the phase 1 study of bone marrow mesenchymal stem cell (MSC) transplantation in 4 patients with cirrhosis. The procedure was safe, and feasible, and led to somewhat promising results (Mohamadnejad M, et al. 2006; Submitted for publication). The aim of this study is to find efficacy of this new treatment strategy in the setting of a multicenter, randomized placebo controlled trial. After assignment of the written informed consent, thirty six patients with decompensated cirrhosis will be enrolled, and will be randomized by block randomization into treatment or placebo arm. All the enrolled patients will be in the waiting list of liver transplantation. In the treatment arm bone marrow of the patients will be aspirated, and autologous bone marrow mesenchymal stem cells will be cultured, and then will be infused through a peripheral vein. Also, the corresponding placebo will be infused for the placebo group. The patients will be followed up for 1 year after performing the procedure.

Eligibility criteria: Inclusion Criteria:

* Cirrhosis (diagnosed by clinical, biochemical, sonographic, and histologic evidences of cirrhosis) (Patients will have histological documentation of cirrhosis before enrollment. However, for those with evidences of severe coagulopathy liver biopsy may not be performed)
* Evidences of decompensated liver disease at screening (e.g. child class B, or C)

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
* Active infectious disease
* Presences of severe underlying cardiac, pulmonary, or renal disease
* Alcohol use in the last 3 months before screening
* Use of hepatotoxic drugs in the last 3 months before screening
* Unwilling to assign the informed consent
* Presence of significant extrahepatic biliary disease (e.g. CBD stone, PSC, etc.)
* Positive HIV ab
* Positive HBsAg with detectable HBV DNA PCR
* Positive HCV Ab with detectable HCV RNA PCR
* Active thrombosis of the portal or hepatic veins
* Serum Cr \> 1.8 mg/dL at screening

Primary outcomes:
measure: MELD score, quality of life, liver volume, histological improvement (In a subset of patients with evidences of clinical and biochemical improvement, follow up liver biopsy will be performed at the end of follow up).
timeFrame: One year
Secondary outcomes:
measure: All cause mortality, tracking the infused cells in the patients' bodies.
timeFrame: One year
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Digestive Disease Research Center, Shariati Hospital
Study officials:
affiliation: Digestive Disease Research Center, Medical Sciences/ University of Tehran
name: Reza Malekzadeh, M.D
role: STUDY_CHAIR
affiliation: Hematology, Oncology, and BMT research center, Medical Sciences/University of Tehran
name: Ardeshir Ghavamzadeh, M.D.
role: STUDY_CHAIR
affiliation: Digestive Disease Research Center, Medical Scineces/ University of Tehran
name: Mehdi Mohamadnejad, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hematology, Oncology, and BMT research center, Medical Sciences/University of Tehran
name: Kamran Alimoghaddam, M.D.
role: PRINCIPAL_INVESTIGATOR
References: