Chronic Rejection of Liver TransplantPhase 1TregNCT01624077
Safety Study of Using Regulatory T Cells Induce Liver Transplantation Tolerance
A Phase 1 study testing Regulatory T cells in people with Chronic Rejection of Liver Transplant, run by Nanjing Medical University at 1 site in China.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 10 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Rejection of Liver Transplant
- What is being tested?
- Regulatory T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteChina
- Study dates
- Dec 2014to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
Read the 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.
- Conditions
- Chronic Rejection of Liver Transplant
- Being tested
- Regulatory T cells
- Keywords
- Regulatory T cells, Liver Transplantation, Rejection, Tolerance, Cell tolerance, Survival
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regulatory T cellsBiological
Also called Treg
Tregs will inject after liver transplantation
| Study group | Role | What they receive |
|---|---|---|
| Regulatory T cells | Experimental | 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. Receives: Biological: Regulatory T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient and graft survival
Measured: one year posttransplantation
Secondary outcomes (3)
Patient and graft survival
Measured: 3 years post transplantation
Incidence rate of biopsy-proven acute or chronic organ rejection
Measured: 3 years post transplantation
Incidence of adverse events associated with liver transplantation and immunosuppression
Measured: 3 years posttransplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2012 (estimated)
- Study startDec 2014
- Primary completionDec 2015 (estimated)
- Study completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Rejection of Liver TransplantStudies of the same condition, open and under way.
- More trials run by Nanjing Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanjing Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Minnesota
- Responsible party
- Principal investigator, Ling Lu, Nanjing Medical University
- Investigators
- Hong Wang, MD, Study chair, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01624077
- Sponsor's protocol ID
- NJLT001
- Acronym
- Treg
- Status last verified
- Dec 2014
- First submitted
- 16 Jan 2012
- Last updated
- 24 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Clinical Trial Using Regulatory T Cells as Individualized Medicine to Promote Donor-specific Clinical Liver Transplantation Tolerance in Nanjing
- ClinicalTrials.gov ID
- NCT01624077
- Acronym / sponsor ID
- Treg / NJLT001
- Conditions
- Chronic Rejection of Liver Transplant
- Keywords
- Regulatory T cells, Liver Transplantation, Rejection, Tolerance, Cell tolerance, Survival
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1 participants (estimated)
- Lead sponsor
- Nanjing Medical UniversityUniversity, hospital or other
- Collaborators
- University of Minnesota
- Study start
- Dec 2014
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 20 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regulatory T cells | Experimental | Biological: Regulatory T cellsNaïve 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. |
Who may qualify
- Ages
- 10 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Regulatory T cellsAlso: TregTregs will inject after liver transplantation | Biological | Regulatory T cells |
Primary outcome
Patient and graft survival
Time frame: one year posttransplantation
3 secondary outcomes
Patient and graft survival
Time frame: 3 years post transplantation
Incidence rate of biopsy-proven acute or chronic organ rejection
Time frame: 3 years post transplantation
Incidence of adverse events associated with liver transplantation and immunosuppression
Time frame: 3 years posttransplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2015.
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Liver Transplant, Hepatitis C
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hong Wang, MD study chair
The First Affiliated Hospital with Nanjing Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Regulatory T cells in people with Chronic Rejection of Liver Transplant, run by Nanjing Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient and graft survival (time frame: one year posttransplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2015.