Safety Study of Autologous Stem Cell in Liver Cirrhosis

Liver Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00382278
• Other study ID #: CELTHEP-01
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: September 28, 2006
• Last updated: April 2, 2008
• Start date: November 2005
• Est. completion date: February 2008

Study information

• Verified date: February 2008
• Source: Universidade Federal do Rio de Janeiro
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: February 2008
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Cirrhosis

Intervention

Procedure:
• Autologous bone marrow-derived mononuclear cells infusion
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. At least 100 millions of mononuclear-enriched BMC suspended in 20 mL of saline were delivered preferentially in the common hepatic artery by celiac trunk catheterism.

Locations

Country	Name	City	State
Brazil	Hospital Universitário Clementino Fraga Filho	Rio de Janeiro

Sponsors (2)

Lead Sponsor	Collaborator
Universidade Federal do Rio de Janeiro	Financiadora de Estudos e Projetos

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in liver function according to Child-Pugh and MELD scores		in days 1,2,7,14,30, 45, 60, 90, 120, 150, 180, 270, 360	Yes
Primary	Hepatic artery and portal vein thrombosis (doppler ultrasound)		in days 1,2,7,14,90, 180 and 360	Yes
Primary	Development of liver nodule (ultrasound screening)		in days 1,2,7,14,90, 180 and 360 (US) and in day 360 (CT scan )	Yes
Primary	Liver related mortality		360 days	Yes
Secondary	Body distribution of 99mTc labeled BMDMC (scintigraphy)		after 3 hours of infusion	No