Effect of BM-MSCs on Chronic AMR After Kidney Transplantation

Kidney Transplantation Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02563340
• Other study ID #: MSC-KTx-cAMR-150926
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: September 26, 2015
• Last updated: September 28, 2015
• Start date: November 2015
• Est. completion date: November 2017

Study information

• Verified date: September 2015
• Source: First Affiliated Hospital, Sun Yat-Sen University
• Contact: Changxi Wang, M.D., Ph.D
• Phone: 86-20-87333428
• Email: wangchx[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Health authority: China: Health and Family Planning Commission of Guangdong Province
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: November 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Other:
• BM-MSCs
BM-MSCs are from third-party healthy donors, and have no HLA alleles similar to renal allograft donors or reacting to positive anti-HLA antibodies in recipients.
• Desensitization therapy (PP, IVIG, rituximab or Bortezomib)
At least one drug or treatment is applied as desensitization therapy to decrease DSA, reduce B cells or inhibit plasma cells, depending on individual condition.

Locations

Country	Name	City	State
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
First Affiliated Hospital, Sun Yat-Sen University	Second Affiliated Hospital of Guangzhou Medical University

Country where clinical trial is conducted

China, 

References & Publications (1)

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. Erratum in: Transplantation. 2014 Mar 27;97(6):e37. Pan, Guanghui [added]. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimated glomerular filtration rate (eGFR)	eGFR at month 12 after enrollment	12 months	No
Secondary	Patient survival rate	patient survival rate at month 12 after enrollment	12 months	No
Secondary	Graft survival rate	graft survival rate at month 12 after enrollment	12 months	No
Secondary	Donor specific antibody (DSA) level	Change of DSA level up to 12 months after enrollment	12 months	No
Secondary	Pathological manifestation	Change of pathological scores according to Banff 2013 criteria	12 months	No
Secondary	Severe adverse events		12 months	Yes

External Links

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