Effect of SVF Derived MSC in DCD Renal Transplantation

Effect of Autologous Stromal Vascular Fraction Derived Mesenchymal Stem Cell in Kidney Transplantation From Chinese Donation After Citizen Death (DCD): A Randomized Controlled Trial

The objective of this trial is to determine if autologous Stromal Vascular Fraction (SVF) derived Mesenchymal Stem Cell (MSC) infusion during and after kidney transplantation from Donation after Citizen Death (DCD) can effectively reduce the need for post transplant immunosuppressant and elevate GFR of allograft. The investigators will infuse autologous SVF derived MSC to the recipients during and after operation to assess the effect of SVF derived MSC and closely monitor renal function, dosage of immunosuppressant, acute rejection, and graft survival. 120 patients eligible for the study as described below will be enrolled, with 60 patients in intervention group and 60 in control group.

Study Overview

• Status: Unknown
• Conditions: Uremia
• Intervention / Treatment: Other: SVFderived MSC transplantations; Drug: Basiliximab

Detailed Description

The objective of this trial is to determine if autologous SVF derived MSC can effectively reduce the need for post transplant immunosuppressant in DCD kidney transplantation. Emphasis will be placed on the safety of autologous SVF derived MSC infusion, dosage of immunosuppressant, GFR, percentage of acute rejection. 120 patients eligible for the study as described below will be enrolled, with 60 patients in intervention group and 60 in control group. Kidneys from the same donor of DCD will be random allocated to intervention group and control group. In intervention group the investigators will collect SVF from recipients with special instruments before transplantation, and culture SVF to abstain MSC. The abstained MSC will be infused to the recipients of DCD kidney transplantation during operation and on 7, 14, 21 POD. The investigators will assess whether induction therapy with autologous SVF derived MSC is feasible in DCD kidney transplantation. The effectiveness of autologous SVF derived MSC induction therapy on reducing of immunosuppressant, reducing the rate of rejection, elevating patient and allograft survival, improving allograft function from day 0 to 12 months after transplantation. Additionally, the investigators will assess the percentage of acute rejection or antibody mediated rejection by Banff criteria, the incidence of delayed graft function (defined as the need for post-transplant dialysis within one week), and the incidence of adverse events including infection, grade 3 and above non-hematologic toxicities, and grade 4 hematologic toxicities.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Recruiting
      • Fuzhou General Hospital, Xiamen Univ
      • Contact: Xia Gao, MD; Phone Number: 8618065102725; Email: 38704163@qq.com
      • Principal Investigator: Jianming Tan, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Uremia patient of any race that is greater than or equal to 18 years of age but less than 60 years old
2. Patient is willing to receive a kidney from DCD
3. 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:

1. 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
2. Patient with prior solid organ transplant or cell transplant (e.g. bone marrow or islet cell).
3. Patient is deemed likely to have a second solid organ transplant or cell transplant (e.g. bone marrow or islet cell) in next 3 years
4. Patient receiving a concurrent SOT (heart, liver, pancreas)
5. ABO incompatible donor recipient pair or CDC crossmatch positive transplant
6. Sensitized patients (most recent anti-HLA Class I or II Panel Reactive Antibodies (PRA)>10% by a CDC-assay) or patients identified a high immunological risk by the transplant physician
7. Donors or recipients are known hepatitis C antibody-positive or polymerase chain reaction (PCR) positive for hepatitis C
8. Donors or recipients are known hepatitis B surface antigen-positive or PCR positive for hepatitis B
9. Donors or recipients are known human immunodeficiency virus (HIV) infection

10. Recipients at risk for tuberculosis (TB)

    • Current clinical, radiographic or laboratory evidence of active or latent TB as determined by local standard of care
    • History of active TB:

    (I). Within the last 2 years, even if treated (II) Greater than 2 years ago, unless there is documentation of adequate treatment according to locally accepted clinical practice c. Recipients at risk of reactivation of TB precludes administration of conventional immunosuppressant (as determined by investigator and based upon appropriate evaluation)

11. Recipients with any significant infection or other contraindication that would preclude transplant
12. Recipients with a history of hypercoagulable state
13. 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.
14. Recipients with active peptic ulcer disease (PUD), chronic diarrhea, or gastrointestinal problem affect absorption
15. Recipients with a history of cancer within the last 5 years (exception: non-melanoma skin cell cancers cured by local resection are permitted)
16. Recipients with a chest radiograph (no more than 2 months prior to randomization) consistent with an acute lung parenchymal process and malignancy
17. Recipients with a hypersensitivity to any study drugs
18. Recipients who have used any investigational drug within 30 days prior to the Day 1 visit
19. Prisoner or patients compulsorily detained (involuntarily incarcerated) for treatment or either a psychiatric or physical (e.g. infectious disease) illness -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SVF(Stromal Vascular Fraction) derived MSC transprlantation; transplantation of autologous SVF derived MSC to the recipients of DCD kidney transplant.; Subjects with uremia in the intervention group will undergo puncture to collect SVF; SVF will be cultured to abstain MSC; The abstained MSC will be infused to the recipients during kidney transplant operation and on 7, 14, and 21 POD.	Other: SVFderived MSC transplantations; infusion of autologous SVF derived MSC to the recipients of DCD kidney transplant. Subjects with uremia in the intervention group will undergo puncture to collect SVF, then SVF will be cultured to abstain MSC, and the abstained MSC will be infused to the recipients during kidney transplant operation and on 7, 14, and 21 POD. And the induction therapy of control group will be Basiliximab.
ACTIVE_COMPARATOR: Basiliximab; induction with Basiliximab during kidney transplantation from DCD	Drug: Basiliximab; induction with Basiliximab before kidney transplantation and on POD 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of autologous SVF derived MSC transplantation on reducing the dosage of CNI by 30% in Kidney Transplantation from Chinese Donation after Citizen Death	Changes of the immunosuppressant by reducing 30% of CNI dosage.	1 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Allograft survival	Allograft survival at 1 year post transplant	1 year
Changes in renal function as determined by eGFR and proteinuria	Changes in renal function as determined by estimated glomerular filtration rate (eGFR) and proteinuria (>1g)	1 year
Incidence of Acute rejection	Incidence of acute rejection (biopsy confirmed acute rejection)	1 year
Incidence of delayed graft function (DGF)	Incidence of delayed graft function (defined as need for post-transplant dialysis within one week)	3 months
SAE (severe adverse effects)	Incidence of death, allograft loss, and hospitalization due to infection at 1 year.	1 year
non-hematologic toxicities	Incidence of grade 3 and above non-hematologic toxicities	1 year

Collaborators and Investigators

• Sponsor: Fuzhou General Hospital
• Investigators: Study Director: Tan Jianming, MD, PhD, Fuzhou General Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (ANTICIPATED): November 1, 2016
• Study Completion (ANTICIPATED): November 1, 2016

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: July 4, 2015
• First Posted (ESTIMATE): July 8, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): July 8, 2015
• Last Update Submitted That Met QC Criteria: July 4, 2015
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: MSC; Kidney transplantation; Stromal Vascular Fraction; DCD
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Uremia; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Basiliximab
• Other Study ID Numbers: SVF-DCD