Induction Therapy With Autologous Mesenchymal Stem Cells for Kidney Allografts

Study Overview
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Brief Summary
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The goal of this study is to evaluate autologous MSCs as an alternative for antibody induction therapy in renal transplantation.

Detailed Description
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Renal transplantation is the most common and successful type of organ transplantation. Induction therapy with antibody plus the maintenance immunosuppressive agents have greatly improved graft survival in renal transplantation. Since mesenchymal stem cells(MSCs)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), we evaluate autologous MSCs as an alternative for antibody induction therapy. Moreover, we examine if MSCs could improve the recovery of early function in transplanted kidney.

Official Title
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Autologous Bone Marrow Mesenchymal Stem Cell Transplantation in Recipients of Living Kidney Allografts

Conditions
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Renal Transplant Rejection

Intervention / Treatment
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* Procedure: Kidney transplantation with MSCs infusion
* Procedure: kidney transplantation without MSC infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be between the ages of 18 and 60 years and meet the institution's criteria for renal transplantation for end-stage renal failure Patient is receiving the first renal transplant Patient is receiving a renal transplant only Women who are of child bearing potential must have a negative pregnancy test (urine test is acceptable) and agree to use reliable contraception for 1 year following transplant Willing to comply with the study visits Be able to sign informed consent document. Note: The subjects do not need to be local residents in order to be eligible for this trial, but must be willing to reside in the area, or within a four hour drive, for the first three months of the protocol so that we can monitor them closely in the early post transplant period. Exclusion Criteria: Previously received or is receiving an organ transplant other than a kidney Significant liver disease, defined as having continuously elevated AST (SGOT) or ALT (SGPT) levels greater than 3 times the upper value of the normal range within 28 days prior to study entry HIV infection. Surface antigen positive for HBV. Antibody positive for hepatitis C virus Recipient or donor is positive for tuberculosis (TB), under treatment for suspected TB, or previously exposed to TB Currently receiving an investigational drug or received an investigational drug within 30 days prior to transplant. Currently receiving any immunosuppressive agent. Clinically active bacterial, fungal, viral or parasitic infection Evidence for immunologic memory against donor. Recipients need antibody induction treatment before the operation. Current cancer or a history of cancer within the 5 years prior to study entry. Serious heart and lung diseases. Patients who's RPR is positive Pregnancy or breastfeeding. Have no ability to communicate. Any form of substance abuse, psychiatric disorder, or other condition that, in opinion of the investigator, may interfere with the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Patients in Group A will receive MSCs instead of anti-interleukin 2 receptor antibody for induction therapy. The first MSCs infusion intravenously will be right at releasing renal artery clamp to establish allograft blood flow and the second infusion of MSCs will be performed two weeks after transplantation. Patients will receive standard regular immunosuppressive agents including calcineurin inhibitor, glucocorticoid, and MMF. | Procedure: Kidney transplantation with MSCs infusion<br>* Patients in Group A will receive the first MSCs infusion intravenously within 24 hours after kidney transplant operation , and the second infusion of MSCs will be performed two weeks later.<br>* Other names: MSCs induction plus a standard or a lower dose of CNI;|
| Active Comparator: B<br>Patients in Group B will receive MSCs instead of anti-interleukin 2 receptor antibody for induction therapy. The first MSCs infusion intravenously will be right at releasing renal artery clamp to establish allograft blood flow and the second infusion of MSCs will be performed two weeks after transplantation. Patients will receive 80% less of calcineurin inhibitor than in Group A. Other immunosuppressive agents such as glucocorticoid and MMF remained the same doses as in Group A. | Procedure: Kidney transplantation with MSCs infusion<br>* Patients in Group A will receive the first MSCs infusion intravenously within 24 hours after kidney transplant operation , and the second infusion of MSCs will be performed two weeks later.<br>* Other names: MSCs induction plus a standard or a lower dose of CNI;|
| Active Comparator: C<br>Patients in Group C will receive anti-interleukin 2 receptor antibody (Basiliximab)for induction therapy. Patients will receive the same doses of regular immunosuppressive agents including calcineurin inhibitor, glucocorticoid, and MMF as in Group A. | Procedure: kidney transplantation without MSC infusion<br>* kidney transplantation with standard immunosuppressive treatment regime<br>* Other names: Anti-IL2R induction therapy with standard dose of CNI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of biopsy-proven acute rejection and early renal function recovery |  | At 1 year post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient and graft survival and prevalence of adverse events |  | At 1 year post-transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplant, Mesenchymal stem cell (MSC)