Effect of BM-MSCs on Chronic AMR After Kidney Transplantation

NCT ID: NCT02563340

Last Updated: 2015-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2017-11-30

Brief Summary

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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

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Conditions

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Kidney Transplantation

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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MSCs group

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.

Group Type EXPERIMENTAL

BM-MSCs

Intervention Type 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.

Desensitization therapy (PP, IVIG, rituximab or Bortezomib)

Intervention Type 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

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.

Group Type ACTIVE_COMPARATOR

Desensitization therapy (PP, IVIG, rituximab or Bortezomib)

Intervention Type 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.

Interventions

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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.

Intervention Type OTHER

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.

Intervention Type OTHER

Other Intervention Names

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allogeneic bone marrow-derived MSCs

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Second Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role collaborator

First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role lead

Responsible Party

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Changxi Wang

Director of Organ Transplant Center

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Changxi Wang, M.D., Ph.D

Role: STUDY_CHAIR

First Affiliated Hospital, Sun Yat-Sen University

Locations

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The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status

Countries

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China

Central Contacts

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Changxi Wang, M.D., Ph.D

Role: CONTACT

Phone: 86-20-87333428

Email: [email protected]

Longshan Liu, M.D., Ph.D

Role: CONTACT

Phone: 86-20-87306082

Email: [email protected]

References

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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.

Reference Type BACKGROUND
PMID: 23263506 (View on PubMed)

Related Links

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Other Identifiers

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MSC-KTx-cAMR-150926

Identifier Type: -

Identifier Source: org_study_id