Effect of BM-MSCs on Early Graft Function Recovery After DCD Kidney Transplant.

Study Overview
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Brief Summary
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This study is designed to investigate whether allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) can promote function recovery in patients with poor early graft function after kidney transplantation from Chinese Donation after Citizen Death (DCD). DCD kidney transplant recipients with poor early graft function (with or without dialysis) post transplant are equally randomized into MSCs group or control group. Patients in MSCs group are administered MSCs treatment. Allogeneic BM-MSCs (1*10^6/kg) from third party are given intravenously for four consecutive doses every week after enrollment. Patients in control group receive placebo. Renal allograft function (eGFR), rejection, patient/graft survival and severe adverse events up to 12 months post enrollment are monitored.

Official Title
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Effect of Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) on Recovery of Poor Early Graft Function Post 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: BM-MSCs
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary kidney transplantation Kidneys are from donation after Chinese citizen death Poor early graft function with or without dialysis after transplantation 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% or 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>Patients with early poor graft function receive allogeneic BM-MSCs at the dose of 1*10^6/kg every week for four consecutive doses. | Other: BM-MSCs<br>* BM-MSCs are from third-party healthy volunteer donors.<br>* Other names: allogeneic bone marrow-derived MSCs;|
| Placebo Comparator: Control group<br>Patients with early poor graft function receive placebo of MSCs, i.e. saline every week for four consecutive doses. | Other: Saline<br>* Saline is the placebo of MSCs in this study.<br>|

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 |
| --- | --- | --- |
| Estimated glomerular filtration rate | eGFR up to 12 months post transplant | 12 months | 
| Proportion of normal renal function recovery |  | 12 months | 
| Time to renal function recovery (days) |  | 12 months | 
| acute rejection rate | Acute rejection rate according to Banff 2013 criteria up to 12 months post transplant | 12 months | 
| patient and graft survival rate | patient and graft survival rate up to 12 months post transplantation | 12 months | 
| Incidence of severe adverse events | Incidence of severe adverse events up to 12 months post transplantation | 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 therapy, poor early graft function, delayed graft function, ischemia reperfusion injury, donation after cardiac death