Effect of BM-MSCs in DCD Kidney Transplantation

Phase 1

• Conditions: Kidney Transplantation; Acute Kidney Tubular Necrosis
• Interventions: Other: bone marrow-derived mesenchymal stem cells; Other: Saline; Drug: Induction therapy (ATG or Basiliximab); Drug: Maintenance therapy (Low-dose CNI + MPA + steroids)

• Registration Number: NCT02561767
• Lead Sponsor: First Affiliated Hospital, Sun Yat-Sen University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2015-09
• Study First Submitted: 2015-09-25
• Study First Submitted QC: 2015-09-25
• Last Update Submitted: 2015-09-25
• Study First Posted: 2015-09-28
• Last Update Posted: 2015-09-28
• Study Start: 2015-10
• Primary Completion: 2016-10
• Study Completion: 2017-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MSCs group	bone marrow-derived mesenchymal stem cells	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.
MSCs group	Induction therapy (ATG or Basiliximab)	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.
MSCs group	Maintenance therapy (Low-dose CNI + MPA + steroids)	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.
Control group	Saline	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.
Control group	Induction therapy (ATG or Basiliximab)	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.
Control group	Maintenance therapy (Low-dose CNI + MPA + steroids)	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.

Primary Outcome Measures

Name	Time	Method
Estimated glomerular filtration rate	1 month	eGFR at one month post-transplant

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The First Affiliated Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China