Human Mesenchymal Stem Cells Induce Liver Transplant Tolerance

May 30, 2013 updated by: Fu-Sheng Wang, Beijing 302 Hospital

Human Umbilical Cord Mesenchymal Stem Cell Induce Liver Allografts Tolerance

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Fu-Sheng Wang, PHD
  • Phone Number: 2015.12 86-10-63879735
  • Email: fswang302@163.com

Study Contact Backup

Study Locations

  • China
      • Beijing, China, 100039
        • Recruiting
        • Beijing 302 Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Fu-Sheng Wang, PHD
        • Sub-Investigator:
          • Zhenwen Liu, Doctor
        • Sub-Investigator:
          • Ming Shi, PHD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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 Names:
  • Immunosuppressive agents plus umbilical cord stem cells
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.
Drug: Conventional plus placebo
Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks.
Other Names:
  • Immunosuppressive agents plus saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence rate of acute rejection and early liver function recovery
Time Frame: 48 weeks
48 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Patient and graft survival, and prevalence of adverse events
Time Frame: 48 weeks
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing 302 Hospital

Investigators

  • Principal Investigator: Fu-Sheng Wang, PHD, Beijing 302 Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (Anticipated)

February 1, 2014

Study Completion (Anticipated)

February 1, 2015

Study Registration Dates

First Submitted

September 19, 2012

First Submitted That Met QC Criteria

September 19, 2012

First Posted (Estimate)

September 21, 2012

Study Record Updates

Last Update Posted (Estimate)

May 31, 2013

Last Update Submitted That Met QC Criteria

May 30, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Beijing302-008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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