Safety Study of Using Regulatory T Cells Induce Liver Transplantation Tolerance (Treg)
Chronic Rejection of Liver Transplant
Biological: Regulatory T cells
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Clinical Trial Using Regulatory T Cells as Individualized Medicine to Promote Donor-specific Clinical Liver Transplantation Tolerance in Nanjing|
- Patient and graft survival [ Time Frame: one year posttransplantation ] [ Designated as safety issue: Yes ]
- Patient and graft survival [ Time Frame: 3 years post transplantation ] [ Designated as safety issue: Yes ]
- Incidence rate of biopsy-proven acute or chronic organ rejection [ Time Frame: 3 years post transplantation ] [ Designated as safety issue: Yes ]
- Incidence of adverse events associated with liver transplantation and immunosuppression [ Time Frame: 3 years posttransplantation ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2014|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Regulatory T cells
Naïve CD4+ T cells isolated from peripheral blood mononuclear cells were stimulated with GMP anti-CD3/CD28 coated beads in the presence of IL-2 ,TGF-β.
Biological: Regulatory T cells
Tregs will inject after liver transplantation
Other Name: Treg
The first trial will involve the generation of CD4+CD25+CD127- Tregs from peripheral blood of pre-transplant patients, followed by a course (up to 24 months) of tacrolimus (5-10 ng/ml) treatment (to prevent chronic rejection) and the administration of the CD4+CD25+CD127- Tregs (1 x 106 cells/kg) at several intervals (for tolerance induction). The immunesuppress drugs will be gradully withdraw within one year. The number of CD4+CD25+ Tregs needed is based on the assumption that the frequencies of alloreactive CD4+ T cells with direct and indirect allospecificity were 1/104 and 1/105, respectively.
The second trial will be carried out in 1-10 year post living donor liver transplantation patients currently under immunosuppressive drug treatment. The investigators will isolate CD4+CD25+CD127- Tregs from these patients, and expand them with mismatched living donor antigens. The patients will be subsequently treated with the expanded donor-antigen specific CD4+CD25+CD127- Tregs (1 x 106 cells/kg) at several intervals, and immunosuppressive drug treatment will be withdrawn.
In both clinical trials, the investigators will monitor the number of allospecific Tregs in patients at different time periods, and to test their suppressive functions in vitro. If there will be any signs of graft rejection, patients will be switched back to immunosuppressive drug treatment. The investigators expect that the innovative Tregs immunosuppressive regimen will lead to achieve permanent liver transplantation tolerance without the use of conventional immunosuppressive drugs: the holygrail in clinical transplantation medicine.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01624077
|Nanjing Medical University|
|Nanjing, Jiangsu, China, 210029|
|Study Chair:||Hong Wang, MD||The First Affiliated Hospital with Nanjing Medical University|