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Effect of BM-MSCs on Chronic AMR After Kidney Transplantation

Phase 1
Conditions
Kidney Transplantation
Interventions
Other: BM-MSCs
Other: Desensitization therapy (PP, IVIG, rituximab or Bortezomib)
Registration Number
NCT02563340
Lead Sponsor
First Affiliated Hospital, Sun Yat-Sen University
Brief Summary

This study is designed to investigate the efficacy and safety of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) on chronic antibody-mediated rejection (cAMR) after kidney transplantation. Chronic AMR is diagnosed according to Banff criteria 2013 based on renal graft biopsy and donor specific antibodies (DSA) examination. cAMR patients are assigned to MSCs group or control group. Patients in control group are prescribed to current desensitization therapy including at least one of the following treatments: plasmapheresis (PP), intravenous immunoglobulin (IVIG), rituximab or Bortezomib, depending on individual pathological and immunological features (eg. DSA type and titer) of each study subjects. Patients in MSCs group receive additional BM-MSCs therapy besides desensitization treatments as in control group. Allogeneic BM-MSCs (1\*10\^6/kg) are intravenously administered every two weeks for four consecutive doses. All cAMR patients are followed up for one year. Renal function, DSA level, pathological features, patient/graft survival, and severe adverse events are monitored during the follow-up period. Immunological features of patients in both groups are consecutively examined.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
60
Inclusion Criteria
  • kidney transplantation
  • cAMR diagnosis is determined based on renal graft biopsy and DSA examination
  • 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
  • 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
  • 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
  • Renal graft function deteriorates due to non-immunological complication, such as surgical issues or drug nephrotoxicity

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MSCs groupDesensitization therapy (PP, IVIG, rituximab or Bortezomib)cAMR patients in this group receive additional intravenous allogeneic BM-MSCs (1\*10\^6/kg) every two weeks for four consecutive doses, besides current desensitization therapy including at least one of the following treatments: plasmapheresis (PP), intravenous immunoglobulin (IVIG), rituximab or Bortezomib.
MSCs groupBM-MSCscAMR patients in this group receive additional intravenous allogeneic BM-MSCs (1\*10\^6/kg) every two weeks for four consecutive doses, besides current desensitization therapy including at least one of the following treatments: plasmapheresis (PP), intravenous immunoglobulin (IVIG), rituximab or Bortezomib.
Control groupDesensitization therapy (PP, IVIG, rituximab or Bortezomib)cAMR patients in this group receive current desensitization therapy including at least one of the following treatments: plasmapheresis (PP), intravenous immunoglobulin (IVIG), rituximab or Bortezomib.
Primary Outcome Measures
NameTimeMethod
Estimated glomerular filtration rate (eGFR)12 months

eGFR at month 12 after enrollment

Secondary Outcome Measures
NameTimeMethod
Graft survival rate12 months

graft survival rate at month 12 after enrollment

Pathological manifestation12 months

Change of pathological scores according to Banff 2013 criteria

Donor specific antibody (DSA) level12 months

Change of DSA level up to 12 months after enrollment

Severe adverse events12 months
Patient survival rate12 months

patient survival rate at month 12 after enrollment

Trial Locations

Locations (1)

The First Affiliated Hospital, Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

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