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Human Mesenchymal Stem Cells Induce Liver Transplant Tolerance

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ClinicalTrials.gov Identifier: NCT01690247
Recruitment Status : Unknown
Verified May 2013 by Fu-Sheng Wang, Beijing 302 Hospital.
Recruitment status was:  Recruiting
First Posted : September 21, 2012
Last Update Posted : May 31, 2013
Sponsor:
Information provided by (Responsible Party):
Fu-Sheng Wang, Beijing 302 Hospital

Tracking Information
First Submitted Date  ICMJE September 19, 2012
First Posted Date  ICMJE September 21, 2012
Last Update Posted Date May 31, 2013
Study Start Date  ICMJE February 2012
Estimated Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2012)
Incidence rate of acute rejection and early liver function recovery [ Time Frame: 48 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2012)
Patient and graft survival, and prevalence of adverse events [ Time Frame: 48 weeks ]
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 Human Mesenchymal Stem Cells Induce Liver Transplant Tolerance
Official Title  ICMJE Human Umbilical Cord Mesenchymal Stem Cell Induce Liver Allografts Tolerance
Brief Summary Liver transplantation is the only lifesaving intervention for patients with end-stage liver diseases. Despite the ability of current immunosuppressive agents to reduce the incidence of acute rejection, the rate of acute rejection reaches to 20-50% after liver transplantation. Furthermore, the long-term toxicity associated with current regimens for liver transplant recipients now is increasingly being perceived as an unmet clinical need. Mesenchymal stem cells (MSC) appeared to be effective in regulating the invoked immune response in setting such as tissue injury, transplantation, and autoimmunity, and have been used successfully to treat graft versus host disease and show immune modulation function both in vitro and in vivo and may help in repairing damaged tissue(s). Here, we evaluate umbilical cord derived MSC (UC-MSC) as an alternative immunosuppressive agents for liver transplanted patients, and examine if UC-MSC could improve the recovery of liver function.
Detailed Description

Liver transplantation is the only lifesaving intervention for patients with end-stage liver diseases. The current immunosuppressive agents reduce the incidence of acute cellular rejection; however, the rate of acute rejection reaches to 20-50% after liver transplantation. Furthermore, the long-term side effects of these regimens now has become a major challenge for liver transplant recipients and is increasingly being perceived as an unmet clinical need, for example, increases in the incidence of bacterial, viral infections, nephrotoxicity with chronic renal impairment, de novo diabetes mellitus, hyperlipidemia, arterial hypertension, cardiovascular disease, osteoporosis, neurotoxicity, hematological toxicity.

Mesenchymal stem cells (MSC) appeared to be effective in regulating the invoked immune response in setting such as tissue injury, transplantation, and autoimmunity, and have been used successfully to treat graft versus host disease and show immune modulation function both in vitro and in vivo and may help in repairing damaged tissue(s). Current clinical trails demonstrated that the use of autologous bone marrow MSC (BM-MSC) for renal transplanted patients resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function. Compared with BM-MSC, umbilical cord derived MSC (UC-MSC) may be the better choice for clinical application. One main reason is that the collection of BM-MSC from liver transplanted patients would be harmful for the patients. Moreover, the proliferative abilities of BM-MSC from patients with liver disease are deficient, whereas, UC-MSC can be obtained from discarded umbilical cords and can be produced on a larger scale. Our and other studies reported that the infusion of human UC-MSC are feasible and can improve liver function of liver fibrosis and liver failure.

The purpose of this study is to learn whether and how UC-MSC can improve the conditions in liver transplanted patients. This study will also look at how well UC-MSC is tolerated and its safety in liver transplanted patients.

Participants in the study will be randomly assigned to one of two treatment arms:

Arm A: Participants will receive 12 weeks of standard regular immunosuppressive agents plus UC-MSC treatment. Arm B: Participants will receive 12 weeks of standard regular immunosuppressive agents plus placebo. UC-MSC will be prepared according to standard procedures and is collected in plastic bags containing anti coagulant. MSCs are given via i.v. under sonography monitoring. After UC-MSC transfusion, patients are followed up at week 4, 8, 12, 24, 36 and 48, and the evaluation of liver function recovery was performed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Evidence of Liver Transplantation
Intervention  ICMJE
  • Drug: Conventional plus UC-MSC
    Received conventional treatment and taken i.v., once per 4 week, at a dose of 1×106 UC-MSC/kg body weight for 12 weeks.
    Other Name: Immunosuppressive agents plus umbilical cord stem cells
  • Drug: Conventional plus placebo
    Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks.
    Other Name: Immunosuppressive agents plus saline
Study Arms  ICMJE
  • Experimental: Conventional plus UC-MSC
    Participants will receive conventional treatment plus a dose of UC-MSC from day 0 through the week 12 study visit. Participants will then be followed until the week 48 study visit
    Intervention: Drug: Conventional plus UC-MSC
  • Placebo Comparator: Conventional plus placebo
    Participants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. Participants will then be followed until the week 48 study visit.
    Intervention: Drug: Conventional plus placebo
Publications *

*   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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: September 19, 2012)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2015
Estimated Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Written informed consent.
  2. Patients must be between the ages of 18 and 70 years and meet the criteria for liver transplantation.
  3. Patient is receiving the first liver transplant.
  4. Patient is receiving a liver transplant only.
  5. Negative pregnancy test (female patients in fertile age).
  6. Willing to comply with the study visits.

Exclusion Criteria:

  1. Previously received or is receiving an organ transplant other than a liver.
  2. Vital organs failure (Cardiac, Renal or Respiratory, et al).
  3. Currently receiving an investigational drug or received an investigational drug within 30 days prior to transplant.
  4. Currently receiving any immunosuppressive agent.
  5. Clinically active bacterial, fungal, viral or parasitic infection.
  6. Pregnant or lactating women.
  7. Other candidates who are judged to be not applicable to this study by investigators.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01690247
Other Study ID Numbers  ICMJE Beijing302-008
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fu-Sheng Wang, Beijing 302 Hospital
Study Sponsor  ICMJE Beijing 302 Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Fu-Sheng Wang, PHD Beijing 302 Hospital
PRS Account Beijing 302 Hospital
Verification Date May 2013

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