Induction With SVF Derived MSC in Living-related Kidney Transplantation

Effect of Autologous Stromal Vascular Fraction Derived Mesenchymal Stem Cell in Living-Related Kidney Transplants: A Randomized Controlled Trial

The objective of this trial is to determine if autologous SVF derived MSC can effectively reduce the need for post transplant immunosuppressant in living-relative kidney transplantation. 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: Living-relative Kidney Transplantation
• Intervention / Treatment: Procedure: SVF-MSC induction; Drug: Basiliximab induction

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 living-relative 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. In interventional group we 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 living-relative kidney transplantation during operation and on 7, 14, 21 POD. We will assess whether induction therapy with autologous SVF derived MSC is feasible in living-relative donor 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, we 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, 350000
      • Recruiting
      • Xi er huan road No.156
      • Contact: Gao Xia, MD; Phone Number: 8659122859175; Email: 38704163@qq.com
      • Contact: Tan Jianming, MD, PhD; Phone Number: 861337598000; Email: doctortjm@yahoo.com

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 a certifiable living-relative donor 18-60 years of age 3. Patient is willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months

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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 with cardiac death (non-heart beating donor) 8 Donors or recipients are known hepatitis C antibody-positive or polymerase chain reaction (PCR) positive for hepatitis C

9. Donors or recipients are known hepatitis B surface antigen-positive or PCR positive for hepatitis B 10. Donors or recipients are known human immunodeficiency virus (HIV) infection 11. Recipients at risk for tuberculosis (TB)

1. Current clinical, radiographic or laboratory evidence of active or latent TB as determined by local standard of care
2. 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) 12. Recipients with any significant infection or other contraindication that would preclude transplant 13. Recipients with a history of hypercoagulabale state 14. 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.

15. Recipients with active peptic ulcer disease (PUD), chronic diarrhea, or gastrointestinal problem affect absorption 16. Recipients with a history of cancer within the last 5 years (exception: non-melanoma skin cell cancers cured by local resection are permitted) 17. Recipients with a chest radiograph (no more than 2 months prior to randomization) consistent with an acute lung parenchymal process and malignancy 18. Recipients with a hypersensitivity to any study drugs 19. Recipients who have used any investigational drug within 30 days prior to the Day 1 visit 20. Prisoner or patients compulsorily detained (involuntarily incarcerated) for treatment or either a psychiatric or physical (e.g. infectious disease) illness

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SVF-MSC induction; collection of autologous SVF; culture of SVF to abstain MSC; infusion of MSC during and after living-relative kidney transplantation	Procedure: SVF-MSC induction; Procedure: infusion of autologous SVF derived MSC to the recipients of living-relative 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
Active Comparator: Basiliximab induction; The control group will be inducted with Basiliximab	Drug: Basiliximab induction; The control group will be inducted with Basiliximab before living-relative 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 immunosuppressant in living-related kidney transplant recipients.	Reducing the dosage of immunosuppressant by 30% of CNI in living-related kidney transplant recipients.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in renal function	• Changes in renal function as determined by estimated glomerular filtration rate (eGFR) and proteinuria (>1g) at 1 year post transplant	1 year
Incidence of acute rejection	Incidence of acute rejection (biopsy confirmed acute rejection according to Banff creteria)	1 year
Incidence of delayed graft function	Incidence of delayed graft function (defined as need for post-transplant dialysis within one week)	1 month
Allograft survival	Allograft survival at 1 year post transplant	1 year
Infection adverse event	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
Hematologic toxicities	Incidence of grade 4 hematologic toxicities	1 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: July 4, 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: July 1, 2015

More Information

Terms related to this study

• Keywords: transplantation; kidney; MSC
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Basiliximab
• Other Study ID Numbers: SVF-LR