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

Primary Purpose

Liver Cirrhosis

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
G-colony stimulating factor
Infusion of the mobilized monocyte cells
Sponsored by
Seoul National University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cirrhosis

Eligibility Criteria

20 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    No Intervention

    Active Comparator

    Experimental

    Arm Label

    Control

    G-colony stimulating factor

    Infusion of the mobilized monocyte cells

    Arm 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 (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.

    Outcomes

    Primary Outcome Measures

    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)

    Secondary Outcome Measures

    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)

    Full Information

    First Posted
    January 2, 2012
    Last Updated
    December 17, 2014
    Sponsor
    Seoul National University Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01503749
    Brief Title
    Safety and Efficacy Study of Peripheral Blood Mononucleated Cells for Treatment of Liver Cirrhosis
    Official Title
    The Role of Peripheral Mononuclear Cells for Treatment of Advanced Liver Cirrhosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2014
    Overall Recruitment Status
    Completed
    Study Start Date
    January 2012 (undefined)
    Primary Completion Date
    July 2013 (Actual)
    Study Completion Date
    August 2014 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Seoul National University Hospital

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Liver Cirrhosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Factorial Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    9 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Control
    Arm Type
    No Intervention
    Arm Description
    Three patients with liver cirrhosis of this arm will not receive any intervention regarding to peripheral blood mononucleated cells.
    Arm Title
    G-colony stimulating factor
    Arm Type
    Active Comparator
    Arm Description
    G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm.
    Arm Title
    Infusion of the mobilized monocyte cells
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    G-colony stimulating factor
    Other Intervention Name(s)
    Filgrastim
    Intervention Description
    G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.
    Intervention Type
    Other
    Intervention Name(s)
    Infusion of the mobilized monocyte cells
    Other Intervention Name(s)
    Filgrastim, leukapheresis
    Intervention Description
    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 Measure Information:
    Title
    Number of Participants With Severe Adverse Events
    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
    Secondary Outcome Measure Information:
    Title
    Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    20 Years
    Maximum Age & Unit of Time
    79 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 20 =< Age < 80 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: HBsAg-positive Active status of hepatocellular carcinoma (HCC) (except patients who have no radiologic evidence of remnant HCC for more than 2 years after treatment) History of hemochromatosis and/or autoimmune hepatitis Pregnant women or lactating women 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 Serum creatinine> 1.5 x normal upper limit or creatinine clearance <60 ml/min Presence of signs of malignant tumors or tumor suspected symptoms, or history of malignant tumors with recurrence rate greater than 20% within two years Gastrointestinal bleeding within the last 3 months or if there is a history of spontaneous bacterial peritonitis Presence of portal vein thrombosis Presence of acute infections
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jung-Hwan Yoon, M.D., Ph. D.
    Organizational Affiliation
    Seoul National University Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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