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Safety and Efficacy Study of Peripheral Blood Mononucleated Cells for Treatment of Liver Cirrhosis

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ClinicalTrials.gov Identifier: NCT01503749
Recruitment Status : Completed
First Posted : January 4, 2012
Results First Posted : December 19, 2014
Last Update Posted : December 19, 2014
Sponsor:
Information provided by (Responsible Party):
Seoul National University Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Liver Cirrhosis
Interventions Drug: G-colony stimulating factor
Other: Infusion of the mobilized monocyte cells
Enrollment 9
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
Arm/Group Title Control G-colony Stimulating Factor Infusion of the Mobilized Peripheral Blood Mononucleated Cells
Hide Arm/Group Description

Three patients with liver cirrhosis of this arm will not receive any intervention regarding to 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.

G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.

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.

Period Title: Overall Study
Started 3 3 3
Completed 3 3 3
Not Completed 0 0 0
Arm/Group Title Control G-colony Stimulating Factor Infusion of the Mobilized Peripheral Blood Mononucleated Cells Total
Hide Arm/Group Description

Three patients with liver cirrhosis of this arm will not receive any intervention regarding to 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.

G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.

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.

Total of all reporting groups
Overall Number of Baseline Participants 3 3 3 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 9 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2
  66.7%
2
  66.7%
1
  33.3%
5
  55.6%
>=65 years
1
  33.3%
1
  33.3%
2
  66.7%
4
  44.4%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 3 participants 9 participants
57
(45 to 65)
62
(59 to 68)
63.3
(54 to 71)
60.8
(45 to 71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 9 participants
Female
1
  33.3%
2
  66.7%
1
  33.3%
4
  44.4%
Male
2
  66.7%
1
  33.3%
2
  66.7%
5
  55.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Korea, Republic of Number Analyzed 3 participants 3 participants 3 participants 9 participants
3 3 3 9
1.Primary Outcome
Title Number of Participants With Severe Adverse Events
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Nine patients who fulfilled the inclusion and exclusion criteria.
Arm/Group Title Control G-colony Stimulating Factor Infusion of the Mobilized Peripheral Blood Mononucleated Cells
Hide Arm/Group Description:

Three patients with liver cirrhosis of this arm will not receive any intervention regarding to 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.

G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.

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.

Overall Number of Participants Analyzed 3 3 3
Measure Type: Number
Unit of Measure: participants
0 0 0
2.Secondary Outcome
Title Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
A total of 9 decompensated cirrhotic patients (5 men and 4 females, age range 45–71 years) grouped by randomization.
Arm/Group Title Control G-colony Stimulating Factor Infusion of the Mobilized Peripheral Blood Mononucleated Cells
Hide Arm/Group Description:

Three patients with liver cirrhosis of this arm will not receive any intervention regarding to 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.

G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.

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.

Overall Number of Participants Analyzed 3 3 3
Mean (Standard Deviation)
Unit of Measure: score
Baseline Child-Pugh score 9  (1) 10  (1) 9  (1)
Child-Pugh score at 24 weeks 9.5  (2.5) 10  (2) 8.3  (1.1)
Baseline MELD score 15.9  (3.2) 18.9  (2.2) 14.4  (2.2)
MELD score at 24 weeks 15.5  (3.9) 24.0  (3.9) 14.7  (3.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control, G-colony Stimulating Factor, Infusion of the Mobilized Peripheral Blood Mononucleated Cells
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame from the baseline till at week 24
Adverse Event Reporting Description

No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24).

No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).

 
Arm/Group Title Control G-colony Stimulating Factor Infusion of the Mobilized Peripheral Blood Mononucleated Cells
Hide Arm/Group Description

Three patients with liver cirrhosis of this arm will not receive any intervention regarding to 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.

G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.

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.

All-Cause Mortality
Control G-colony Stimulating Factor Infusion of the Mobilized Peripheral Blood Mononucleated Cells
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Control G-colony Stimulating Factor Infusion of the Mobilized Peripheral Blood Mononucleated Cells
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/3 (0.00%)      0/3 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Control G-colony Stimulating Factor Infusion of the Mobilized Peripheral Blood Mononucleated Cells
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      1/3 (33.33%)      1/3 (33.33%)    
Blood and lymphatic system disorders       
gum bleeding * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0
Gastrointestinal disorders       
nausea * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0
diarrhea * 1  2/3 (66.67%)  2 0/3 (0.00%)  0 0/3 (0.00%)  0
Hepatobiliary disorders       
ascties tapping * 1  2/3 (66.67%)  4 1/3 (33.33%)  1 0/3 (0.00%)  0
Liver transplantation * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders       
percutaneous vertebroplasty * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0
Nervous system disorders       
hepatic encephalopathy * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1
Renal and urinary disorders       
hyperkalemia * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, otherwise specified.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Pf. Jung-Hwan Yoon
Organization: Seoul National University Hospital
Phone: 82-2-2072-2228
Responsible Party: Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01503749     History of Changes
Other Study ID Numbers: PBMC
First Submitted: January 2, 2012
First Posted: January 4, 2012
Results First Submitted: November 27, 2014
Results First Posted: December 19, 2014
Last Update Posted: December 19, 2014