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

Phase 1

Completed

• Conditions: Liver Cirrhosis
• Interventions: Drug: G-colony stimulating factor; Other: Infusion of the mobilized monocyte cells

• Registration Number: NCT01503749
• Lead Sponsor: Seoul National University Hospital

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.

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2012-01
• Study First Submitted: 2012-01-02
• Study First Submitted QC: 2012-01-03
• Study First Posted: 2012-01-04
• Primary Completion: 2013-07
• Study Completion: 2014-08
• Status Verified: 2014-10
• Results First Submitted: 2014-11-27
• Results First Submitted QC: 2014-12-17
• Last Update Submitted: 2014-12-17
• Results First Posted: 2014-12-19
• Last Update Posted: 2014-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
G-colony stimulating factor	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.
Infusion of the mobilized monocyte cells	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)