Mesenchymal Stem Cell Transplantation in Decompensated Cirrhosis

University of Tehran

Status and phase

Completed

Phase 2

Conditions

Cirrhosis

Treatments

Procedure: Autologous mesenchymal stem cell transplantation

Study type

Interventional

Funder types

Other

Identifiers

NCT00476060

DDRC85-13

Details and patient eligibility

About

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.

Full 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.

Enrollment

27 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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