Effect of SVF Derived MSC in DCD Renal Transplantation

Uremia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02492490
• Other study ID #: SVF-DCD
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: May 20, 2015
• Last updated: July 4, 2015
• Start date: December 2014
• Est. completion date: November 2016

Study information

• Verified date: November 2014
• Source: Fuzhou General Hospital
• Contact: Tan Jianming, MD PhD
• Phone: 8613375918000
• Email: tanjm156[@]yahoo.com
• Is FDA regulated: No
• Health authority: Health and Family Planning Commission of Fujian Province: China
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Uremia

Intervention

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.

Drug:
• Basiliximab
induction with Basiliximab before kidney transplantation and on POD 4

Locations

Country	Name	City	State
China	Fuzhou General Hospital, Xiamen Univ	Fuzhou	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Fuzhou General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	Incidence of Acute rejection	Incidence of acute rejection (biopsy confirmed acute rejection)	1 year	Yes
Secondary	Incidence of delayed graft function (DGF)	Incidence of delayed graft function (defined as need for post-transplant dialysis within one week)	3 months	Yes
Secondary	Allograft survival	Allograft survival at 1 year post transplant	1 year	Yes
Secondary	SAE (severe adverse effects)	Incidence of death, allograft loss, and hospitalization due to infection at 1 year.	1 year	Yes
Secondary	non-hematologic toxicities	Incidence of grade 3 and above non-hematologic toxicities	1 year	Yes