Liver Cirrhosis
Conditions
Brief summary
The investigators aim to investigate the safety and efficacy of peripheral blood monocyte for the treatment of patients with advanced liver cirrhosis.
Detailed description
G-colony stimulating factor(5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis. On the day 4th, plasmapheresis will be done to collect peripheral blood mononucleated cells . And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance.
Interventions
DRUGG-colony stimulating factor
G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.
OTHERInfusion of the mobilized monocyte cells
G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells. And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance.
Sponsors
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
1. 20 =\< Age \< 80 2. Advanced liver cirrhosis with Child-Pugh score 8 or 9 (including patients who have no radiologic evidence of remnant HCC for more than 2 years after treatment)
Exclusion criteria
1. HBsAg-positive 2. Active status of hepatocellular carcinoma (HCC) (except patients who have no radiologic evidence of remnant HCC for more than 2 years after treatment) 3. History of hemochromatosis and/or autoimmune hepatitis 4. Pregnant women or lactating women 5. Hemoglobin \< 8g/dL (male), 7.5g/dL (female) or white blood cell (WBC) \<1,500 mm3 or Neutrophils \<500/mm3 or platelet count \<50,000/mm3 6. Serum creatinine\> 1.5 x normal upper limit or creatinine clearance \<60 ml/min 7. Presence of signs of malignant tumors or tumor suspected symptoms, or history of malignant tumors with recurrence rate greater than 20% within two years 8. Gastrointestinal bleeding within the last 3 months or if there is a history of spontaneous bacterial peritonitis 9. Presence of portal vein thrombosis 10. Presence of acute infections
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Severe Adverse Events | up to 6 months | No serious adverse event. Minor adverse events (not considered to be related to this study), as follows; Control: 6 events (ascites and pleural tapping, gum bleeding, ascties tapping x3, diarrhea) G-colony stimulating factor group: 6 events (percutaneous vertebroplasty, abdominal pain and nausea, hyperkalemia, ascties tapping, diarrhea, liver transplantation) Infusion of the mobilized peripheral blood mononucleated cells group: 1 event (hepatic encephalopathy) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | Baseline and Week 24 | The efficacy (mean change in Child-Pugh score and Model For End-Stage Liver Disease score \[at weeks 24\]) of ultrasound-guided percutaneous portal transplantation of peripheral blood monocyte cell in cirrhotic patients. MELD Score = (0.957 \* ln(Serum Cr) + 0.378 \* ln(Serum Bilirubin) + 1.120 \* ln(INR) + 0.643 ) \* 10 (if hemodialysis, value for Creatinine is automatically set to 4.0) (minimum \<9: 1.9% mortality; maximum 40 or more: 71.3% mortality). Child-Pugh score = Bilirubin (mg/dl): \<2 (1 point),2-3 (2 points), \>3 (3 points) + Albumin (g/dl): \>3.5 (1 point),3.5-2.8 (2 points), \<2.8 (3 points) + PT prolongation (INR): \<4 seconds (\<1.7) (1 point), 4-6 seconds (1.7-2.3) (2 points),\>6 seconds (\>2.3) (3 points) + Ascites: Absent (1 point), Slight (2 points), Moderate (3 points) + Encephalopathy: Absent (1 point), Mild (I-II) (2 points), Severe (III-IV) (3 points) ; Class A: 5-6, Class B: 7-9, Class C: 10-15 (minimum 5, maximum 15; higher Child-Pugh score with worse prognosis) |
Participant flow
Recruitment details
Recruitment location: single medical center (Seoul National University Hospital) Recruitment period: between February 2012 and July 2013
Pre-assignment details
Number of total enrolled pariticipants: 9 Number of screened participants: 14 Number of dropped participants: 5 (Withdraw consent:4, etc:1 due to development of hepatocellular carcinoma) Number of completed participants: 9
Participants by arm
| Arm | Count |
|---|---|
| Control Three patients with liver cirrhosis of this arm will not receive any intervention regarding to peripheral blood mononucleated cells
. | 3 |
| G-colony Stimulating Factor G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm.
G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm. | 3 |
| Infusion of the Mobilized Peripheral Blood Mononucleated Cells G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells
. And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance.
Infusion of the mobilized peripheral blood mononucleated cells: G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells. And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance. | 3 |
| Total | 9 |
Baseline characteristics
| Characteristic | G-colony Stimulating Factor | Infusion of the Mobilized Peripheral Blood Mononucleated Cells | Control | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Age, Continuous | 62 years | 63.3 years | 57 years | 60.8 years |
| Region of Enrollment Korea, Republic of | 3 participants | 3 participants | 3 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 1 / 3 | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Number of Participants With Severe Adverse Events
No serious adverse event. Minor adverse events (not considered to be related to this study), as follows; Control: 6 events (ascites and pleural tapping, gum bleeding, ascties tapping x3, diarrhea) G-colony stimulating factor group: 6 events (percutaneous vertebroplasty, abdominal pain and nausea, hyperkalemia, ascties tapping, diarrhea, liver transplantation) Infusion of the mobilized peripheral blood mononucleated cells group: 1 event (hepatic encephalopathy)
Time frame: up to 6 months
Population: Nine patients who fulfilled the inclusion and exclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Number of Participants With Severe Adverse Events | 0 participants |
| G-colony Stimulating Factor | Number of Participants With Severe Adverse Events | 0 participants |
| Infusion of the Mobilized Peripheral Blood Mononucleated Cells | Number of Participants With Severe Adverse Events | 0 participants |
Secondary
Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score
The efficacy (mean change in Child-Pugh score and Model For End-Stage Liver Disease score \[at weeks 24\]) of ultrasound-guided percutaneous portal transplantation of peripheral blood monocyte cell in cirrhotic patients. MELD Score = (0.957 \* ln(Serum Cr) + 0.378 \* ln(Serum Bilirubin) + 1.120 \* ln(INR) + 0.643 ) \* 10 (if hemodialysis, value for Creatinine is automatically set to 4.0) (minimum \<9: 1.9% mortality; maximum 40 or more: 71.3% mortality). Child-Pugh score = Bilirubin (mg/dl): \<2 (1 point),2-3 (2 points), \>3 (3 points) + Albumin (g/dl): \>3.5 (1 point),3.5-2.8 (2 points), \<2.8 (3 points) + PT prolongation (INR): \<4 seconds (\<1.7) (1 point), 4-6 seconds (1.7-2.3) (2 points),\>6 seconds (\>2.3) (3 points) + Ascites: Absent (1 point), Slight (2 points), Moderate (3 points) + Encephalopathy: Absent (1 point), Mild (I-II) (2 points), Severe (III-IV) (3 points) ; Class A: 5-6, Class B: 7-9, Class C: 10-15 (minimum 5, maximum 15; higher Child-Pugh score with worse prognosis)
Time frame: Baseline and Week 24
Population: A total of 9 decompensated cirrhotic patients (5 men and 4 females, age range 45-71 years) grouped by randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | Baseline Child-Pugh score | 9 score | Standard Deviation 1 |
| Control | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | Child-Pugh score at 24 weeks | 9.5 score | Standard Deviation 2.5 |
| Control | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | Baseline MELD score | 15.9 score | Standard Deviation 3.2 |
| Control | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | MELD score at 24 weeks | 15.5 score | Standard Deviation 3.9 |
| G-colony Stimulating Factor | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | MELD score at 24 weeks | 24.0 score | Standard Deviation 3.9 |
| G-colony Stimulating Factor | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | Baseline Child-Pugh score | 10 score | Standard Deviation 1 |
| G-colony Stimulating Factor | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | Baseline MELD score | 18.9 score | Standard Deviation 2.2 |
| G-colony Stimulating Factor | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | Child-Pugh score at 24 weeks | 10 score | Standard Deviation 2 |
| Infusion of the Mobilized Peripheral Blood Mononucleated Cells | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | MELD score at 24 weeks | 14.7 score | Standard Deviation 3.4 |
| Infusion of the Mobilized Peripheral Blood Mononucleated Cells | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | Child-Pugh score at 24 weeks | 8.3 score | Standard Deviation 1.1 |
| Infusion of the Mobilized Peripheral Blood Mononucleated Cells | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | Baseline MELD score | 14.4 score | Standard Deviation 2.2 |
| Infusion of the Mobilized Peripheral Blood Mononucleated Cells | Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | Baseline Child-Pugh score | 9 score | Standard Deviation 1 |
p-value: >0.05t-test, 2 sided