Effect of BM-MSCs in DCD Kidney Transplantation

Sun Yat-sen University

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Acute Kidney Tubular Necrosis; Kidney Transplantation

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02561767

MSCs-KTx-DCD-150924

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Primary kidney transplantation
2. Receiving induction therapy and combined immunosuppressive regimens (CNIs + MPA + steroids)
3. 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

1. Secondary kidney transplantation
2. Combined or multi-organ transplantation
3. 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
4. Panel reactive antibody (PRA)>20%
5. CDC crossmatch is positive
6. Donors or recipients are known hepatitis C antibody-positive or polymerase chain reaction (PCR) positive for hepatitis C
7. Donors or recipients are known hepatitis B surface antigen-positive or PCR positive for hepatitis B
8. Donors or recipients are known human immunodeficiency virus (HIV) infection
9. Patients with active infection
10. 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.
11. Patients with severe cardiovascular dysfunction
12. WBC<3*10^9/L or RBC <5g/dL
13. Highly allergic constitution or having severe history of allergies.
14. Patients with active peptic ulcer disease, chronic diarrhea, or gastrointestinal problem affect absorption
15. Patients with a history of cancer within the last 5 years
16. Prisoner or patients compulsorily detained (involuntarily incarcerated) for treatment or either a psychiatric or physical (e.g. infectious disease) illness

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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120 participants in 2 patient groups, including a placebo group

MSCs group

Experimental group

Description:

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.

Treatment:

Drug: Induction therapy (ATG or Basiliximab)

Other: bone marrow-derived mesenchymal stem cells

Drug: Maintenance therapy (Low-dose CNI + MPA + steroids)

Control group

Placebo Comparator group

Description:

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.

Treatment:

Other: Saline

Drug: Induction therapy (ATG or Basiliximab)

Drug: Maintenance therapy (Low-dose CNI + MPA + steroids)