Liver Cirrhosis
Conditions
Keywords
Adult stem cells, Liver disease, CD34 positive cells
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.
Interventions
PROCEDURELeukapheresis
PROCEDUREInfusion of stem cells via image guided scan
Sponsors
Imperial College London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Autologous stem cells
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events Related to Injection | Day 1 to Day 60 | Incidence of serious adverse event related to injection with the study participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Liver Function | Day 1 to Day 60 | Number of participant that have liver function improvement in liver function |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were sequentially recruited to the study from January 2005 to June 2005
Participants by arm
| Arm | Count |
|---|---|
| Autologous Stem Cells Male or female aged from 20 years to 65 years with evidence of chronic liver failure, abnormal serum albumin and/or bilirubin and/or prothrombin time | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Autologous Stem Cells |
|---|---|
| Age, Continuous | 49 years |
| Count of Participants | 5 Participants |
| Region of Enrollment United Kingdom | 5 participants |
| Sex: Female, Male Gender Female | 1 Participants |
| Sex: Female, Male Gender Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Number of Participants With Serious Adverse Events Related to Injection
Incidence of serious adverse event related to injection with the study participants
Time frame: Day 1 to Day 60
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Autologous Stem Cells | Number of Participants With Serious Adverse Events Related to Injection | 0 Participants |
Secondary
Improvement in Liver Function
Number of participant that have liver function improvement in liver function
Time frame: Day 1 to Day 60
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Autologous Stem Cells | Improvement in Liver Function | 5 Participants |