Safety Study of Autologous Stem Cell in Liver Cirrhosis

Condition(s) targeted: Liver Cirrhosis

Intervention: Autologous bone marrow-derived mononuclear cells infusion (Procedure)

Phase: Phase 1/Phase 2

Status: Terminated

Sponsored by: Federal University of Rio de Janeiro

Official(s) and/or principal investigator(s):
Guilherme FM Rezende, MD, PhD, Principal Investigator, Affiliation: Federal University of Rio de Janeiro

It is a fase I/II clinical study to evaluate feasibility, safety and kinetics of cellular therapy with bone marrow-derived mononuclear cells (ABMMC) in patients with liver cirrhosis. All the patients have moderate liver disfunction and a waiting time expectancy of liver transplantation longer than 12 months due their low MELD score. The ABMMC are labeled with 99mTc and infused through the hepatic artery. Scintigraphy is performed 2 and 24 hours after infusion. Patients are submitted to frequent clinical, laboratorial and image evaluation during the follow up period of 12 months.

Official title: Phase 1/2 Study of Autologous Bone Marrow Derived Mononuclear Cells in Liver Cirrhosis

Study design: Treatment, Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

Primary outcome:

Changes in liver function according to Child-Pugh and MELD scores

Hepatic artery and portal vein thrombosis (doppler ultrasound)

Development of liver nodule (ultrasound screening)

Liver related mortality

Secondary outcome: Body distribution of 99mTc labeled BMDMC (scintigraphy)

Detailed description: A one year clinical trial was conducted. Patients had moderate liver dysfunction and a liver transplant was not expected to occur earlier than 12 months, due to low MELD scores. Hepatocellular carcinoma (HCC) and hepatic artery or portal vein thrombosis were excluded by color Doppler ultrasonography (DUS) and 3-phase computed tomography (CT). Under local anesthesia, 100 mL of bone marrow were aspirated from the posterior iliac crest. ABMMC were isolated by density gradient centrifugation in Ficoll-Hypaque gradient, 10% of the cells were labeled with SnCl2-99mTc, and a small fraction was used for cell counting and viability analysis. ABMMC were delivered preferentially in the common hepatic artery by celiac trunk catheterism. Total body scintigraphy (TBS) was performed 3 hours after infusion. Patients were submitted to frequent clinical, biochemical and imaging evaluation during follow up.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Liver cirrhosis of any origin

- Moderate liver disfunction (Child-Pugh Score=7-10)

Exclusion Criteria:

- Waiting time expectancy of liver transplant shorter than 12 months

- Ongoing hepatic encephalopathy

- Clinically detectable ascitis

- Severe coagulation disorder (INR>2,0 or platelets count < 40. 000)

- Diagnosis or strong suspicion of cancer (except basocellular)

- Pregnancy or intention to become pregnant during the next 12 months

- Moderate or severe co-morbidity

- Current participation in another clinical trial

Hospital Universitário Clementino Fraga Filho, Rio de Janeiro 21941-590, Brazil

Starting date: November 2005
Ending date: February 2008
Last updated: April 2, 2008