Effect of BM-MSCs in DCD Kidney Transplantation

Study Overview
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Brief Summary
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This study is designed to determine the efficacy and safety of allogeneic bone marrow-derived mesenchymal stem cells in kidney transplantation from Chinese donation after citizen's death (DCD). A pair uremia patients receiving kidney grafts from a same donor are randomized into two groups: MSCs group and control group. Besides routine induction therapy (ATG or Basiliximab) and maintenance immunosuppressive drugs (low-dose Tacrolimus + MPA + prednisone), patients in MSCs group are administered MSCs treatment (1*10^6/kg). Allogeneic bone marrow-derived MSCs (1*10^6/kg) are given intravenously at day 0 (post renal reperfusion during surgery), day 7, day 14 and day 21. The renal allograft function, rejection, patient/graft survival and severe adverse events within 12 months post-transplant are monitored.

Official Title
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The Efficacy and Safety of Bone Marrow-derived Mesenchymal Stem Cells in Kidney Transplantation From Chinese Donation After Citizen Death (DCD): A Multi-center Randomized Controlled Trial

Conditions
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Kidney Transplantation, Acute Kidney Tubular Necrosis

Intervention / Treatment
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* Other: bone marrow-derived mesenchymal stem cells
* Other: Saline
* Drug: Induction therapy (ATG or Basiliximab)
* Drug: Maintenance therapy (Low-dose CNI + MPA + steroids)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary kidney transplantation Receiving induction therapy and combined immunosuppressive regimens (CNIs + MPA + steroids) Patient is willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months Exclusion Criteria: Secondary kidney transplantation Combined or multi-organ transplantation Women who are pregnant, intend to become pregnant in the next 1 years, breastfeeding, or have a positive pregnancy test on enrollment or prior to study medication administration Panel reactive antibody (PRA)>20% CDC crossmatch is positive Donors or recipients are known hepatitis C antibody-positive or polymerase chain reaction (PCR) positive for hepatitis C Donors or recipients are known hepatitis B surface antigen-positive or PCR positive for hepatitis B Donors or recipients are known human immunodeficiency virus (HIV) infection Patients with active infection Recipients with a history of substance abuse (drugs or alcohol) within the past 6 months, or psychotic disorders that are not capable with adequate study follow-up. Patients with severe cardiovascular dysfunction WBC<3*10^9/L or RBC <5g/dL Highly allergic constitution or having severe history of allergies. Patients with active peptic ulcer disease, chronic diarrhea, or gastrointestinal problem affect absorption Patients with a history of cancer within the last 5 years Prisoner or patients compulsorily detained (involuntarily incarcerated) for treatment or either a psychiatric or physical (e.g. infectious disease) illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSCs group<br>Allogeneic bone marrow-derived mesenchymal stem cells (10^6/kg) from third party donors is intravenously given at day 0 (after renal artery reperfusion), day 7, day 14 and day 21.Induction therapy: ATG or Basiliximab; Maintenance therapy: low-dose Tacrolimus + mycophenolic acid + prednisone. The third-party MSCs have no similar HLA alleles of kidney donors, and have no HLA alleles specific to preformed anti-HLA antibodies in recipients prior to KTx. | Other: bone marrow-derived mesenchymal stem cells<br>* BM-MSCs is harvested from third-party health volunteer donors.<br>* Other names: BM-MSCs;Drug: Induction therapy (ATG or Basiliximab)<br>* ATG, antithymocyte globulin; Basiliximab, anti-CD25 mAb. Recipients receive ATG or Basiliximab as induction therapy in both MSCs group and control group.<br>* Other names: ATG or Basiliximab;Drug: Maintenance therapy (Low-dose CNI + MPA + steroids)<br>* Maintenance immunosuppressive therapy consists of low-dose tacrolimus and mycophenolic acid and steroids. Recipients receive the same maintenance therapy in both MSCs group and control group.<br>* Other names: Low-dose tacrolimus + Mycophenolic acid (MPA) + steroids;|
| Placebo Comparator: Control group<br>Placebo (saline) is intravenously given at day 0 (after renal artery reperfusion), day 7, day 14 and day 21. Induction therapy: ATG or Basiliximab; Maintenance therapy: low-dose Tacrolimus + mycophenolic acid + prednisone. | Other: Saline<br>* Saline as placebo of MSCs<br>Drug: Induction therapy (ATG or Basiliximab)<br>* ATG, antithymocyte globulin; Basiliximab, anti-CD25 mAb. Recipients receive ATG or Basiliximab as induction therapy in both MSCs group and control group.<br>* Other names: ATG or Basiliximab;Drug: Maintenance therapy (Low-dose CNI + MPA + steroids)<br>* Maintenance immunosuppressive therapy consists of low-dose tacrolimus and mycophenolic acid and steroids. Recipients receive the same maintenance therapy in both MSCs group and control group.<br>* Other names: Low-dose tacrolimus + Mycophenolic acid (MPA) + steroids;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated glomerular filtration rate | eGFR at one month post-transplant | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of slow graft function |  | 12 months | 
| Incidence of delayed graft function |  | 12 months | 
| Proportion of normal renal function recovery |  | 12 months | 
| Time to renal function recovery |  | 12 months | 
| Patient survival |  | 12 months | 
| Renal graft survival |  | 12 months | 
| Incidence of acute rejection |  | 12 months | 
| Severe adverse events |  | 12 months | 
| Estimated glomerular filtration rate | eGFR up to 12 months post-transplant | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney transplantation, mesenchymal stem cell, donation after citizen's death, ischemia reperfusion injury, renal function recovery