Safety Study of Using Regulatory T Cells Induce Liver Transplantation Tolerance (Treg)

This study is currently recruiting participants.
Verified June 2012 by Nanjing Medical University
Sponsor:
Collaborator:
University of Minnesota - Clinical and Translational Science Institute
Information provided by (Responsible Party):
Ling Lu, Nanjing Medical University
ClinicalTrials.gov Identifier:
NCT01624077
First received: January 16, 2012
Last updated: June 16, 2012
Last verified: June 2012

January 16, 2012
June 16, 2012
May 2011
August 2012   (final data collection date for primary outcome measure)
Patient and graft survival [ Time Frame: one year posttransplantation ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01624077 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Safety Study of Using Regulatory T Cells Induce Liver Transplantation Tolerance
Phase 1 Clinical Trial Using Regulatory T Cells as Individualized Medicine to Promote Donor-specific Clinical Liver Transplantation Tolerance in Nanjing

The first trial will involve the generation of donor alloantigen-specific CD4+CD25+ Tregs from peripheral blood of pre-transplant patients, the administration of the CD4+CD25+ Tregs (1 x 106 cells/kg) at several intervals (for graft specific tolerance induction).

The first trial will involve the generation of donor alloantigen-specific CD4+CD25+ Tregs from peripheral blood of pre-transplant patients, the use of alemtuzumab (30 mg i.v.) or ATG as pre-conditioning for lymphocyte depletion (and/or additional injections after transplantation), followed by a brief course (up to 6 months) of tacrolimus (5-10 ng/ml) treatment (to prevent acute rejection) and the administration of the CD4+CD25+ Tregs (1 x 106 cells/kg) at several intervals (for tolerance induction). 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+ 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+ 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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Rejection of Liver Transplant
Biological: regulatory T cells
Tregs will inject after liver transplantation
Other Name: Treg
Experimental: Regulatory T cells
Naïve CD4+ T cells isolated from peripheral blood mononuclear cells were stimulated with anti-CD3/CD28 coated beads in the presence of IL-2 ,TGF-β and DC.
Intervention: Biological: regulatory T cells
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1
December 2014
August 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Weight greater than 50kg
  • Will be receiving a living-related primary liver allograft
  • Negative B-cell and T-cell cytotoxic and flow cytometry crossmatch
  • Normal echocardiogram (ECG) with an ejection fraction of greater than 50%
  • Parents willing to comply with the study visits

Exclusion Criteria:

  • Current active infection
  • Pregnant or breastfeeding
  • Evidence of HIV infection or known HIV positive serology
  • Antibody positive for hepatitis C virus
  • Surface antigen positive for HBV
  • Recipient or donor is positive for tuberculosis (TB), under treatment for suspected TB, or previously exposed to TB (positive Mantoux test)
  • Current cancer or a history of cancer
  • Uncontrolled concomitant infections, severe diarrhea, vomiting, active upper gastrointestinal tract malabsorption, active peptic ulcer, or any other unstable medical condition that could interfere with this study
  • Currently receiving an investigational drug or received an investigational drug within 30 days prior to transplant
  • Currently receiving any immunosuppressive agent
  • Anticipated contraindication to taking medications orally or via nasogastric tube by the morning of Day 2 following completion of the transplant procedure
  • Require certain medications
  • Known hypersensitivity to any of the study medications,
  • Any form of substance abuse, psychiatric disorder, or other condition that, in opinion of the investigator, may interfere with the study
  • Anticipated contraindication to study medications administration for longer than 5 days post-transplant
  • History of rejection after organ transplantation
  • Muti-organ transplantation
  • Autoimmune disease
Both
10 Years to 60 Years
Yes
Contact: ling lu, MD 86-25-68136053 lvling@njmu.edu.cn
China
 
NCT01624077
NJLT001
Yes
Ling Lu, Nanjing Medical University
Nanjing Medical University
University of Minnesota - Clinical and Translational Science Institute
Study Chair: Hong Wang, MD Jiangsu Province Hospital
Nanjing Medical University
June 2012

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