Clinical trial NCT02563340: Effect of BM-MSCs on Chronic AMR After Kidney Transplantation
Official title: Efficacy and Safety of Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) on Chronic Antibody-mediated Rejection (cAMR) After Kidney Transplantation: A Multi-center Perspective Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Kidney Transplantation
Keywords: kidney transplantation
antibody-mediated rejection
mesenchymal stem cell therapy
donor specific antibody
acute rejection
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital of Guangzhou Medical University
First posted: 2015-09-30
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: 12 months
Secondary outcomes:
measure: Patient survival rate
timeFrame: 12 months
measure: Graft survival rate
timeFrame: 12 months
measure: Donor specific antibody (DSA) level
timeFrame: 12 months
measure: Pathological manifestation
timeFrame: 12 months
measure: Severe adverse events
timeFrame: 12 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Changxi Wang, M.D., Ph.D
role: STUDY_CHAIR
References:
citation: Peng Y, Ke M, Xu L, Liu L, Chen X, Xia W, Li X, Chen Z, Ma J, Liao D, Li G, Fang J, Pan G, Xiang AP. Donor-derived mesenchymal stem cells combined with low-dose tacrolimus prevent acute rejection after renal transplantation: a clinical pilot study. Transplantation. 2013 Jan 15;95(1):161-8. doi: 10.1097/TP.0b013e3182754c53.