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

The Role of Peripheral Mononuclear Cells for Treatment of Advanced Liver Cirrhosis

The investigators aim to investigate the safety and efficacy of peripheral blood monocyte for the treatment of patients with advanced liver cirrhosis.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Drug: G-colony stimulating factor; Other: Infusion of the mobilized monocyte cells

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Three patients with liver cirrhosis of this arm will not receive any intervention regarding to peripheral blood mononucleated cells.
Active Comparator: 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.	Drug: G-colony stimulating factor; G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.; Other Names: Filgrastim
Experimental: Infusion 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.	Other: Infusion 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.; Other Names: Filgrastim; leukapheresis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Jung-Hwan Yoon, M.D., Ph. D., Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: January 2, 2012
• First Submitted That Met QC Criteria: January 3, 2012
• First Posted (Estimate): January 4, 2012

Study Record Updates

• Last Update Posted (Estimate): December 19, 2014
• Last Update Submitted That Met QC Criteria: December 17, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: PBMC