Effect of BM-MSCs in DCD Kidney Transplantation

NCT02561767 | Unknown Phase 1

• 1 other identifier: MSCs-KTx-DCD-150924
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to determine the efficacy and safety of allogeneic bone marrow-derived mesenchymal stem cells in kidney transplantation from Chinese donation after citizen's death (DCD). A pair uremia patients receiving kidney grafts from a same donor are randomized into two groups: MSCs group and control group. Besides routine induction therapy (ATG or Basiliximab) and maintenance immunosuppressive drugs (low-dose Tacrolimus + MPA + prednisone), patients in MSCs group are administered MSCs treatment (1\*10\^6/kg). Allogeneic bone marrow-derived MSCs (1\*10\^6/kg) are given intravenously at day 0 (post renal reperfusion during surgery), day 7, day 14 and day 21. The renal allograft function, rejection, patient/graft survival and severe adverse events within 12 months post-transplant are monitored.

Conditions

Kidney Transplantation; Acute Kidney Tubular Necrosis

Keywords

kidney transplantation; mesenchymal stem cell; donation after citizen's death; ischemia reperfusion injury; renal function recovery

Outcome Measures

Primary Outcomes (1)

• Estimated glomerular filtration rate

  eGFR at one month post-transplant

  1 month

Secondary Outcomes (9)

• Incidence of slow graft function

  12 months

• Incidence of delayed graft function

  12 months

• Proportion of normal renal function recovery

  12 months

• Time to renal function recovery

  12 months

• Patient survival

  12 months

Study Arms (2)

MSCs group

EXPERIMENTAL

Allogeneic bone marrow-derived mesenchymal stem cells (10\^6/kg) from third party donors is intravenously given at day 0 (after renal artery reperfusion), day 7, day 14 and day 21.Induction therapy: ATG or Basiliximab; Maintenance therapy: low-dose Tacrolimus + mycophenolic acid + prednisone. The third-party MSCs have no similar HLA alleles of kidney donors, and have no HLA alleles specific to preformed anti-HLA antibodies in recipients prior to KTx.

Other: bone marrow-derived mesenchymal stem cells; Drug: Induction therapy (ATG or Basiliximab); Drug: Maintenance therapy (Low-dose CNI + MPA + steroids)

Control group

PLACEBO COMPARATOR

Placebo (saline) is intravenously given at day 0 (after renal artery reperfusion), day 7, day 14 and day 21. Induction therapy: ATG or Basiliximab; Maintenance therapy: low-dose Tacrolimus + mycophenolic acid + prednisone.

Other: Saline; Drug: Induction therapy (ATG or Basiliximab); Drug: Maintenance therapy (Low-dose CNI + MPA + steroids)

Interventions

bone marrow-derived mesenchymal stem cells OTHER

BM-MSCs is harvested from third-party health volunteer donors.

Also known as: BM-MSCs

MSCs group

Saline OTHER

Saline as placebo of MSCs

Control group

Induction therapy (ATG or Basiliximab) DRUG

ATG, antithymocyte globulin; Basiliximab, anti-CD25 mAb. Recipients receive ATG or Basiliximab as induction therapy in both MSCs group and control group.

Also known as: ATG or Basiliximab

Control group; MSCs group

Maintenance therapy (Low-dose CNI + MPA + steroids) DRUG

Maintenance immunosuppressive therapy consists of low-dose tacrolimus and mycophenolic acid and steroids. Recipients receive the same maintenance therapy in both MSCs group and control group.

Also known as: Low-dose tacrolimus + Mycophenolic acid (MPA) + steroids

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:

• Primary kidney transplantation
• Receiving induction therapy and combined immunosuppressive regimens (CNIs + MPA + steroids)
• 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:

• Secondary kidney transplantation
• 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
• Panel reactive antibody (PRA)\>20%
• CDC crossmatch is positive
• 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

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

Conditions

Kidney Tubular Necrosis, Acute; Reperfusion Injury

Interventions

Sodium Chloride; Neoadjuvant Therapy; Basiliximab; Maintenance; cni protein, Drosophila; Steroids; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Acute Kidney Injury; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Combined Modality Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Health Care Facilities Workforce and Services; Fused-Ring Compounds; Polycyclic Compounds; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

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: 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 25, 2015
• First Posted: September 28, 2015
• Study Start: October 1, 2015
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2017
• Last Updated: September 28, 2015

Record last verified: 2015-09

Locations

CN (1)