Clinical trial NCT00147043: Adult Stem Cell Therapy in Liver Insufficiency
Official title: Adult Stem Therapy for Patients With Liver Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Cirrhosis
Keywords: Adult stem cells
Liver disease
CD34 positive cells
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2005-09-07
Enrollment: 5
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Autologous stem cells
Primary purpose: TREATMENT

Brief summary: In order to determine the clinical application potential of adult stem cells we propose to investigate the safety and toxicity of infusing adult stem cells in the hepatic artery or portal vein of five patients with chronic liver insufficiency and to identify any clinical benefit if such occurs.

Objectives:

1. To assess safety and treatment related toxicities
2. To determine clinical benefit or deterioration by monitoring changes in liver function

Detailed description: The liver in an adult healthy body maintains a balance between cell gain and cell loss. Though normally proliferatively quiescent, hepatocyte loss such as that caused by partial hepatectomy, uncomplicated by virus infection or inflammation, invokes a rapid regenerative response to restore liver mass. This restoration of moderate cell loss and 'wear and tear' renewal is largely achieved by hepatocyte self-replication. More severe liver injury can activate a potential stem cell compartment located within the intrahepatic biliary tree, giving rise to cords of bipotential, so-called, oval cells within the lobules that can differentiate into hepatocytes and biliary epithelial cells. A third population of stem cells with hepatic potential reside in the bone marrow; these haematopoietic stem cells can contribute to the albeit low renewal rate of hepatocytes, make a more significant contribution to regeneration and even completely restore normal function in a murine model of hereditary tyrosinaemia.

A recent abstract has suggested that an astonishingly high number of bone marrow cells (\~25% of liver parenchyma occupied by bone marrow-derived cells) will engraft and differentiate into hepatocytes in a model of cirrhosis in the mouse when injected intravenously. More importantly, this bone marrow infusion resulted in significant improvements in liver function (serum albumin) within the cirrhotic animals.

This is a safety and toxicity study in five patients with chronic liver disease. Each will receive autologous stem cells 10 to the sixth cells via the hepatic artery or portal vein under image guided scanning. Patients will be followed for a total of 60 days.

Eligibility criteria: Inclusion Criteria:

- Male or female aged from 20 years to 65 years Evidence of chronic liver failure Abnormal serum albumin and/or bilirubin and/or prothrombin time Unsuitable for liver transplantation WHO performance status \<2 Women of childbearing potential may be included but must use a reliable and appropriate contraceptive method Life expectancy of at least three months Ability to give informed consent

Exclusion Criteria:

- Patients aged below 20 years or above 65 years Pregnant or lactating women Patients with recent recurrent gastrointestinal bleeding Spontaneous bacterial peritonitis Evidence of active infection HIV infection Patients unable to give informed consent

Primary outcomes:
measure: Number of Participants With Serious Adverse Events Related to Injection
timeFrame: Day 1 to Day 60
Secondary outcomes:
measure: Improvement in Liver Function
timeFrame: Day 1 to Day 60
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Hammersmith Hospitals NHS Trust
Study officials:
affiliation: Imperial College London
name: Nagy Habib, ChM FRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gordon MY, Levicar N, Pai M, Bachellier P, Dimarakis I, Al-Allaf F, M'Hamdi H, Thalji T, Welsh JP, Marley SB, Davies J, Dazzi F, Marelli-Berg F, Tait P, Playford R, Jiao L, Jensen S, Nicholls JP, Ayav A, Nohandani M, Farzaneh F, Gaken J, Dodge R, Alison M, Apperley JF, Lechler R, Habib NA. Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor. Stem Cells. 2006 Jul;24(7):1822-30. doi: 10.1634/stemcells.2005-0629. Epub 2006 Mar 23.