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Mesenchymal Stem Cells After Renal or Liver Transplantation

Primary Purpose

Liver Failure, Kidney Failure

Status
Completed
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
Mesenchymal Stem Cells
Sponsored by
University of Liege
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Failure focused on measuring end-stage, liver diseases, cirrhosis, cancer, fulminant hepatic failure, metabolic hepatic diseases, congenital hepatic diseases, renal diseases

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female patients between 18 and 75 years of age, who will undergo first Kidney Transplantation or whole Liver Transplantation from a cadaveric or donation after cardiac death (DCD) organ donor;
  • Fertile female patients must use a reliable contraception method;
  • Informed consent given by patient or his/next of kin if the patient is unable to give informed consent, for the complete (MSC + follow-up) or partial(no MSC + follow-up) study;
  • Successful liver/kidney transplantation, demonstration of organ function (improvement of INR in liver recipients and of creatinine in kidney recipients at 24-36h) and normal graft vasculature at Doppler examination.

Exclusion Criteria:

  • Past history of malignant disease, with the exception of hepatocarcinoma within the Milan criteria for the Liver Transplantation patients;
  • Active uncontrolled infection;
  • HIV or HCV positive;
  • EBV-negative;
  • Retransplantation;
  • Combined transplantation;
  • Living related transplantation or split liver transplantation;
  • Autoimmune disease or expected impossibility to wean immunosuppression (Liver Transplantation) or corticosteroids (Kidney Transplantation);
  • Endotracheal intubation;
  • Postoperative cardiovascular instability, active hemorrhage, or any other serious clinical complication between transplantation and evaluation for suitability for MSC infusion;
  • For Kidney Transplantation: panel reactive antibodies (PRA) >50%.

Sites / Locations

  • University Hospital Liege

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

MSC Liver Transplantation

MSC Kidney Transplantation

Arm Description

Patients undergoing a first liver transplantation. Beside receiving standard liver tranplantation care (antibacterial and viral prophylactic treatments as well as a standard immunosuppressive regime i.e. tacrolimus, mycophenolate mofetil and steroids), patients will be infused with 1,5-3,0 10E6 MSC/kg on postoperative day 3+/-2

Patients undergoing a first kidney transplantation. Beside receiving standard kidney tranplantation care (antibacterial and viral prophylactic treatments as well as a standard immunosuppressive regime i.e. tacrolimus, mycophenolate mofetil and steroids associated with ant-IL-2 antibodies), patients will be infused with 1,5-3,0 10E6 MSC/kg on postoperative day 3+/-2.

Outcomes

Primary Outcome Measures

Infusional toxicity
Incidence, timing and severity of any clinical complication related to MSC infusion, including pulmonary events or immune reactions.
Incidence of infections (bacterial, viral, fungal, parasitic) and cancers
Incidence, timing and severity of any infection (bacterial, viral, fungal, parasitic) (blood hemoculture, urine culture, PCR CMV, PCR BK virus at month 1,2,3) Incidence, timing and severity of malignant disease (Posttransplant lymphoproliferative disorder or other)

Secondary Outcome Measures

Patient and graft survivals
Effects of MSC on graft function
Liver Transplantation: bilirubin, INR, transaminases, GGT, at day 7, months 1, 3, 6, 9, 12. Kidney Transplanttaion: number of post transplant hemodialysis, creatinine at day 7, months 1, 3, 6, 9, 12.
Biopsy-proven (Banff classification) rejection rates
At months 3, 6, 9, 12.
Feasibility and safety of weaning or decreasing immunosuppression
Decision points at months 3, 6, 9, 12.
Recipient's immune function
To evaluate recipient's immune function (T cell blood populations (including T regs) by FACS, TREC quantification, Vβ repertoire diversity, pathogen-specific T cells, anti-organ donor HLA antibodies).
Anti-MSC donor HLA antibodies.
To evaluate the potential development of anti-MSC donor HLA antibodies.

Full Information

First Posted
September 1, 2011
Last Updated
June 13, 2022
Sponsor
University of Liege
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1. Study Identification

Unique Protocol Identification Number
NCT01429038
Brief Title
Mesenchymal Stem Cells After Renal or Liver Transplantation
Official Title
Infusion of Third-party Mesenchymal Stem Cells After Renal or Liver Transplantation. A Phase I-II, Open-label, Clinical Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
February 1, 2012 (Actual)
Primary Completion Date
March 11, 2019 (Actual)
Study Completion Date
March 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Liege

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The immune system of a patient can attack the liver or the kidney received from a donor (organ rejection). This can be prevented by treating these patients long-life with immunosuppressive drugs. Unfortunately, these drugs lead to numerous side effects and fail to prevent the rejection occurring months later after the transplantation (chronic rejection). Recently, it has been shown that a particular type of cells present in the bone marrow, namely Mesenchymal Stem Cells (MSC), when injected to a patient, suppress its immune system and increase success rates of blood cells transplantation. This outcome opens doors to investigate the potential of these cells to provide a valuable tool for improving solid organ transplantation without the need of high concentration of immunosuppressive drugs. The present project aims at evaluating the safety and tolerability of MSC administration after liver or kidney transplantation.
Detailed Description
The present project aims at evaluating the safety and tolerability of third party MSC administration after liver or kidney organ transplantation. Ten patients undergoing liver transplantation and 10 patients undergoing kidney transplantation will be included in the experimental arm to receive a single infusion of MSC. The outcome of each of these 2 subgroups will be compared with that of similar control patients undergoing liver or kidney transplantation but who will not receive MSC. Liver and kidney transplanted patients will receive standard immunosuppressive therapy, TAC-MMF-steroïds and TAC-MMF-steroïds plus an IL-2-R antibody respectively. Patients enrolled in the experimental arms will be infused with a single dose of 1,5-3,0 10E6 MSC/kg, 3(+/-2) days after the transplantation. Weaning of immunosuppression will be attempted from month 6 in liver transplant patients who did not present a rejection episode and show normal graft function and graft biopsy. Kidney transplant patients will continue standard immunosuppressive therapy indefinitely. Male or female (>18 years) individuals unrelated to the recipient or the graft donor will be MSC donors. MSC donors need to fulfill generally accepted criteria for allogeneic HSC donation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Failure, Kidney Failure
Keywords
end-stage, liver diseases, cirrhosis, cancer, fulminant hepatic failure, metabolic hepatic diseases, congenital hepatic diseases, renal diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MSC Liver Transplantation
Arm Type
Experimental
Arm Description
Patients undergoing a first liver transplantation. Beside receiving standard liver tranplantation care (antibacterial and viral prophylactic treatments as well as a standard immunosuppressive regime i.e. tacrolimus, mycophenolate mofetil and steroids), patients will be infused with 1,5-3,0 10E6 MSC/kg on postoperative day 3+/-2
Arm Title
MSC Kidney Transplantation
Arm Type
Experimental
Arm Description
Patients undergoing a first kidney transplantation. Beside receiving standard kidney tranplantation care (antibacterial and viral prophylactic treatments as well as a standard immunosuppressive regime i.e. tacrolimus, mycophenolate mofetil and steroids associated with ant-IL-2 antibodies), patients will be infused with 1,5-3,0 10E6 MSC/kg on postoperative day 3+/-2.
Intervention Type
Biological
Intervention Name(s)
Mesenchymal Stem Cells
Other Intervention Name(s)
MSC
Intervention Description
Third party MSC 1,5-3,010E6/kg. No HLA matching between MSC donor and the recipient or the liver/kidney donor. One infusion at day 3+/-2.
Primary Outcome Measure Information:
Title
Infusional toxicity
Description
Incidence, timing and severity of any clinical complication related to MSC infusion, including pulmonary events or immune reactions.
Time Frame
Within 24 hours of infusion
Title
Incidence of infections (bacterial, viral, fungal, parasitic) and cancers
Description
Incidence, timing and severity of any infection (bacterial, viral, fungal, parasitic) (blood hemoculture, urine culture, PCR CMV, PCR BK virus at month 1,2,3) Incidence, timing and severity of malignant disease (Posttransplant lymphoproliferative disorder or other)
Time Frame
Continuously over 2 years
Secondary Outcome Measure Information:
Title
Patient and graft survivals
Time Frame
Continuously over 2 years
Title
Effects of MSC on graft function
Description
Liver Transplantation: bilirubin, INR, transaminases, GGT, at day 7, months 1, 3, 6, 9, 12. Kidney Transplanttaion: number of post transplant hemodialysis, creatinine at day 7, months 1, 3, 6, 9, 12.
Time Frame
over 1 year
Title
Biopsy-proven (Banff classification) rejection rates
Description
At months 3, 6, 9, 12.
Time Frame
over 1 year
Title
Feasibility and safety of weaning or decreasing immunosuppression
Description
Decision points at months 3, 6, 9, 12.
Time Frame
continuously over 2 years
Title
Recipient's immune function
Description
To evaluate recipient's immune function (T cell blood populations (including T regs) by FACS, TREC quantification, Vβ repertoire diversity, pathogen-specific T cells, anti-organ donor HLA antibodies).
Time Frame
over 1 year
Title
Anti-MSC donor HLA antibodies.
Description
To evaluate the potential development of anti-MSC donor HLA antibodies.
Time Frame
over 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients between 18 and 75 years of age, who will undergo first Kidney Transplantation or whole Liver Transplantation from a cadaveric or donation after cardiac death (DCD) organ donor; Fertile female patients must use a reliable contraception method; Informed consent given by patient or his/next of kin if the patient is unable to give informed consent, for the complete (MSC + follow-up) or partial(no MSC + follow-up) study; Successful liver/kidney transplantation, demonstration of organ function (improvement of INR in liver recipients and of creatinine in kidney recipients at 24-36h) and normal graft vasculature at Doppler examination. Exclusion Criteria: Past history of malignant disease, with the exception of hepatocarcinoma within the Milan criteria for the Liver Transplantation patients; Active uncontrolled infection; HIV or HCV positive; EBV-negative; Retransplantation; Combined transplantation; Living related transplantation or split liver transplantation; Autoimmune disease or expected impossibility to wean immunosuppression (Liver Transplantation) or corticosteroids (Kidney Transplantation); Endotracheal intubation; Postoperative cardiovascular instability, active hemorrhage, or any other serious clinical complication between transplantation and evaluation for suitability for MSC infusion; For Kidney Transplantation: panel reactive antibodies (PRA) >50%.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yves Beguin, MD, PhD
Organizational Affiliation
CHU-ULg
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Liege
City
Liege
ZIP/Postal Code
4000
Country
Belgium

12. IPD Sharing Statement

Citations:
PubMed Identifier
28284916
Citation
Detry O, Vandermeulen M, Delbouille MH, Somja J, Bletard N, Briquet A, Lechanteur C, Giet O, Baudoux E, Hannon M, Baron F, Beguin Y. Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study. J Hepatol. 2017 Jul;67(1):47-55. doi: 10.1016/j.jhep.2017.03.001. Epub 2017 Mar 9.
Results Reference
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Mesenchymal Stem Cells After Renal or Liver Transplantation

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