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Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis

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ClinicalTrials.gov Identifier: NCT03109236
Recruitment Status : Recruiting
First Posted : April 12, 2017
Last Update Posted : April 12, 2017
Sponsor:
Collaborators:
Singapore General Hospital
Tan Tock Seng Hospital
Changi General Hospital
Information provided by (Responsible Party):
National University Hospital, Singapore

Tracking Information
First Submitted Date  ICMJE March 6, 2017
First Posted Date  ICMJE April 12, 2017
Last Update Posted Date April 12, 2017
Estimated Study Start Date  ICMJE April 15, 2017
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2017)
  • Improvement of Fibrosis Staging (Ishak) [ Time Frame: 3 months ]
    Improvement of Fibrosis Staging (Ishak) > 1 point
  • Improvement of liver fibrosis on MRE (magnetic resonance elastography) [ Time Frame: 6 months ]
    Improvement of liver fibrosis on MRE (magnetic resonance elastography) > 2 point
  • Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State [ Time Frame: 6 months ]
    Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State by at least 2 points
  • Improvement of quantitative fibrosis [ Time Frame: 1 year ]
    Improvement of quantitative fibrosis on histology > 10%
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2017)
  • Overall Survival and Improvement [ Time Frame: 1 year ]
    Overall Survival
  • Overall Improvement in Liver Function Tests [ Time Frame: 1 year ]
    Improvement in Liver Function Tests, especially Total Bilirubin, Albumin and Prothrombin Time
  • Improvement of Hepatic Venous Pressure [ Time Frame: 3 months ]
    Improvement of Hepatic Venous Pressure
  • Incidence of clinical decompensation [ Time Frame: 1 year ]
    Frequency of Incidence of clinical decompensation
  • Overall Improvement of Patient Reported outcome [ Time Frame: 6 months ]
    Improvement of Patient Reported outcome (quality of life Short Form Health Survey SF-36 for liver cirrhosis)
  • Overall Improvement of MELD score [ Time Frame: 1 year ]
    Rate of deterioration of MELD score (Kaplan Meier analysis)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis
Official Title  ICMJE Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis
Brief Summary This proposal translates a hypothesis driven basic research into clinical setting to determine the potential of using autologous CD133+ cells to reverse fibrosis and improve clinical outcome for patients with end stage cirrhosis. This has significant impact on the management of cirrhosis.
Detailed Description

This is a 2 arm randomised study patients with decompensated liver cirrhosis involving minimum of 23 and maximum of 33 patients in each arm.

The investigators propose that transplantation of mobilized autologous CD133+ cells harvested from the bone marrow directly into the liver has the ability to replace and regenerate the damaged sinusoidal endothelium as well as normalize macrophage and Natural Killer (NK) cell function. The niche provided by the refenestrated endothelium can polarize the macrophage to antifibrotic phenotype as well as directly inactivate the activated myofibroblast, resulting in reversal of liver fibrosis and improvement in liver function. Transplantation of cells will be via intraportal route delivered by percutaneous cannulation of the portal vein system.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a 2 arm randomised study patients with decompensated liver cirrhosis involving 33 patients in each arm. Randomisation will be done by statistician to determine which arm patients will be in (control / treatment).

Treatment arm:

Patient will undergo CD133+ cells transplantation at stable compensated state. 5 dose Granulocyte Colony Stimulating Factor (GCSF) will be administered 5 days consecutively before bone marrow harvesting.

Approximately 250ml of bone marrow will be harvested and subjected to CD133 isolation using clinimacs (Miltenyi Biotec) in a closed system

Under ultrasound guidance, 50 mls of 50-100 million CD133 cells will be infused directly through transhepatic route into portal venous circulation of the liver over 5 mins.

Control Arm:

Patients will receive 5 doses of GCSF

Masking: Single (Outcomes Assessor)
Masking Description:
Blinding will be maintained by investigators performing analysis of the results. Given the invasive procedure of percutaneous transhepatic cannulation, the investigators felt that it will be unethical to perform sham procedure on control arm patients. Both managing doctors and patient will know which arm they are on but where not inevitable, data collection such as quality of life and results interpretation such as histology and laboratory analysis of results will be performed anonymously.
Primary Purpose: Treatment
Condition  ICMJE End Stage Liver Disease
Intervention  ICMJE
  • Drug: Neupogen
    5 doses of GCSF injection will be injected under the skin on the abdomen to mobilize the bone marrow cells.
    Other Name: GCSF
  • Procedure: CD133 Cells Transplantation
    Endothelial progenitor cells are harvested by CD133+ MACS (magnetic activated cell sorting) sort selection of bone marrow and a minimum of 1x 10^6 and up to 50-100 x 10^6 cells are transplanted to one lobe of the liver via a percutaneous catheter inserted into the portal venous system by percutaneous transhepatic approach for engraftment.
    Other Name: Endothelial Progenitor cells
Study Arms  ICMJE
  • Experimental: Treatment

    Patient will undergo CD133+ cells transplantation at stable compensated state. 5 dose GCSF (Neupogen) will be administered 5 days consecutively before bone marrow harvesting.

    Approximately 250ml of bone marrow will be harvested and subjected to CD133 isolation using clinimacs (Miltenyi Biotec) in a closed system Under ultrasound guidance, 50 mls of 50-100 million CD133 cells will be infused directly through transhepatic route into portal venous circulation of the liver over 5 mins.

    Interventions:
    • Drug: Neupogen
    • Procedure: CD133 Cells Transplantation
  • Active Comparator: Control

    Non-Transplant Arm:

    Patients will receive 5 doses of GCSF (Neupogen)

    Intervention: Drug: Neupogen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 5, 2017)
66
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2021
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Liver cirrhosis of any aetiology but where active disease is controlled
  • Childs B/C with Child-Pugh score > 8
  • MELD score 13-27
  • Platelet>50 000/mls

Exclusion Criteria:

  • MELD score >27
  • Abdominal ascites precluding percutaneous transhepatic cannulation.
  • HIV
  • History of hematological or hepatic malignancy
  • Other underlying malignancy with <1 year survival
  • Absence of systemic diseases that may impact survival within 1 year.
  • Listed or potential for liver transplant
  • Pregnant women
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nur Halisah 66015193 mdcnhj@nus.edu.sg
Contact: Dan Yock Young 67727641 yock_young_dan@nuhs.edu.sg
Listed Location Countries  ICMJE Singapore
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03109236
Other Study ID Numbers  ICMJE 2016/00711
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National University Hospital, Singapore
Study Sponsor  ICMJE National University Hospital, Singapore
Collaborators  ICMJE
  • Singapore General Hospital
  • Tan Tock Seng Hospital
  • Changi General Hospital
Investigators  ICMJE
Principal Investigator: Dan Yock Young National University Hospital, Singapore
Principal Investigator: Mark Muthiah National University Hospital, Singapore
PRS Account National University Hospital, Singapore
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP