Effect of BM-MSCs on Chronic AMR After Kidney Transplantation

NCT02563340 | Unknown Phase 1

• 1 other identifier: MSC-KTx-cAMR-150926
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Transplantation

Keywords

kidney transplantation; antibody-mediated rejection; mesenchymal stem cell therapy; donor specific antibody; acute rejection

Outcome Measures

Primary Outcomes (1)

• Estimated glomerular filtration rate (eGFR)

  eGFR at month 12 after enrollment

  12 months

Secondary Outcomes (5)

• Patient survival rate

  12 months

• Graft survival rate

  12 months

• Donor specific antibody (DSA) level

  12 months

• Pathological manifestation

  12 months

• Severe adverse events

  12 months

Study Arms (2)

MSCs group

EXPERIMENTAL

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.

Other: BM-MSCs; Other: Desensitization therapy (PP, IVIG, rituximab or Bortezomib)

Control group

ACTIVE COMPARATOR

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.

Other: Desensitization therapy (PP, IVIG, rituximab or Bortezomib)

Interventions

BM-MSCs OTHER

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.

Also known as: allogeneic bone marrow-derived MSCs

MSCs group

Desensitization therapy (PP, IVIG, rituximab or Bortezomib) OTHER

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.

Control group; MSCs group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• First Affiliated Hospital, Sun Yat-Sen University: lead
• Second Affiliated Hospital of Guangzhou Medical University: collaborator

Study Sites (1)

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

Related 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.

  PMID: 23263506 BACKGROUND

Related Links

• Previous publication

MeSH Terms

Interventions

Desensitization, Psychologic; Immunoglobulins, Intravenous; Rituximab; Bortezomib

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Changxi Wang, M.D., Ph.D

  First Affiliated Hospital, Sun Yat-Sen University

  STUDY CHAIR

Central Study Contacts

Changxi Wang, M.D., Ph.D

CONTACT

86-20-87333428; wangchx@mail.sysu.edu.cn

Longshan Liu, M.D., Ph.D

CONTACT

86-20-87306082; liulshan@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Organ Transplant Center

Study Record Dates

• First Submitted: September 26, 2015
• First Posted: September 30, 2015
• Study Start: November 1, 2015
• Primary Completion: October 1, 2017
• Study Completion: November 1, 2017
• Last Updated: September 30, 2015

Record last verified: 2015-09

Locations

CN (1)