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

February 21, 2015 updated by: Ling Lu, Nanjing Medical University

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).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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specific CD4+CD25+CD127- Tregs (1 x 106 cells/kg) at several intervals, and immunosuppressive drug treatment will be withdrawn.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.

Study Type

Interventional

Enrollment (Anticipated)

1

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 Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Nanjing Medical University

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

10 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Treg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Patient and graft survival
Time Frame: one year posttransplantation
one year posttransplantation

Secondary Outcome Measures

Outcome Measure
Time Frame
Patient and graft survival
Time Frame: 3 years post transplantation
3 years post transplantation
Incidence rate of biopsy-proven acute or chronic organ rejection
Time Frame: 3 years post transplantation
3 years post transplantation
Incidence of adverse events associated with liver transplantation and immunosuppression
Time Frame: 3 years posttransplantation
3 years posttransplantation

Collaborators and Investigators

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

Sponsor

Nanjing Medical University

Collaborators

University of Minnesota

Investigators

  • Study Chair: Hong Wang, MD, The First Affiliated Hospital with Nanjing Medical University

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

December 1, 2014

Primary Completion (Anticipated)

December 1, 2015

Study Completion (Anticipated)

December 1, 2015

Study Registration Dates

First Submitted

January 16, 2012

First Submitted That Met QC Criteria

June 16, 2012

First Posted (Estimate)

June 20, 2012

Study Record Updates

Last Update Posted (Estimate)

February 24, 2015

Last Update Submitted That Met QC Criteria

February 21, 2015

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • NJLT001

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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