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Mesenchymal Stem Cells After Renal or Liver Transplantation

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ClinicalTrials.gov Identifier: NCT01429038
Recruitment Status : Unknown
Verified January 2013 by Yves Beguin, University Hospital of Liege.
Recruitment status was:  Recruiting
First Posted : September 5, 2011
Last Update Posted : January 21, 2013
Sponsor:
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Liver Failure Kidney Failure Biological: Mesenchymal Stem Cells Phase 1 Phase 2

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Infusion of Third-party Mesenchymal Stem Cells After Renal or Liver Transplantation. A Phase I-II, Open-label, Clinical Study
Study Start Date : February 2012
Estimated Primary Completion Date : February 2016
Estimated Study Completion Date : February 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: MSC Liver Transplantation
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
Biological: Mesenchymal Stem Cells
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.
Other Name: MSC
Experimental: MSC Kidney Transplantation
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.
Biological: Mesenchymal Stem Cells
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.
Other Name: MSC


Outcome Measures

Primary Outcome Measures :
  1. Infusional toxicity [ Time Frame: Within 24 hours of infusion ]
    Incidence, timing and severity of any clinical complication related to MSC infusion, including pulmonary events or immune reactions.

  2. Incidence of infections (bacterial, viral, fungal, parasitic) and cancers [ Time Frame: Continuously over 2 years ]
    • 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 :
  1. Patient and graft survivals [ Time Frame: Continuously over 2 years ]
  2. Effects of MSC on graft function [ Time Frame: over 1 year ]
    • 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.

  3. Biopsy-proven (Banff classification) rejection rates [ Time Frame: over 1 year ]
    At months 3, 6, 9, 12.

  4. Feasibility and safety of weaning or decreasing immunosuppression [ Time Frame: continuously over 2 years ]
    Decision points at months 3, 6, 9, 12.

  5. Recipient's immune function [ Time Frame: over 1 year ]
    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).

  6. Anti-MSC donor HLA antibodies. [ Time Frame: over 1 year ]
    To evaluate the potential development of anti-MSC donor HLA antibodies.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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%.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01429038


Contacts
Contact: Yves Beguin, MD, PhD +32/4/3667201 yves.beguin@chu.ulg.ac.be
Contact: Olivier Detry, MD, PhD +32/4/3667111 oli.detry@chu.ulg.ac.be

Locations
Belgium
University Hospital Liege Recruiting
Liege, Belgium, 4000
Contact: Yves Beguin, MD, PhD    32 43667201    yves.beguin@chu.ulg.ac.be   
Contact: Olivier Detry, MD, PhD    32 43667111    oli.detry@chu.ulg.ac.be   
Sub-Investigator: Chantal Lechanteur, PhD         
Sub-Investigator: Etienne Baudoux, MD         
Sub-Investigator: Olivier Detry, MD, PhD         
Sub-Investigator: Frédéric Baron, MD,PhD         
Sub-Investigator: Arnaud Deroover, MD         
Sub-Investigator: Jean-Paul Squifflet, MD         
Sub-Investigator: Pierre Honoré, MD, PhD         
Sub-Investigator: Michel Meurisse, MD, PhD         
Sub-Investigator: Catherine Bonvoisin, MD         
Sub-Investigator: Laurent Weekers, MD         
Sub-Investigator: Joan Somja, MD         
Sub-Investigator: Philippe Delvenne, MD, PhD         
Sponsors and Collaborators
University Hospital of Liege
Investigators
Principal Investigator: Yves Beguin, MD, PhD CHU-ULg
More Information

Responsible Party: Yves Beguin, Prof, University Hospital of Liege
ClinicalTrials.gov Identifier: NCT01429038     History of Changes
Other Study ID Numbers: TJT1106P1
First Posted: September 5, 2011    Key Record Dates
Last Update Posted: January 21, 2013
Last Verified: January 2013

Keywords provided by Yves Beguin, University Hospital of Liege:
end-stage
liver diseases
cirrhosis
cancer
fulminant hepatic failure
metabolic hepatic diseases
congenital hepatic diseases
renal diseases

Additional relevant MeSH terms:
Renal Insufficiency
Liver Failure
Kidney Diseases
Urologic Diseases
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Liver Extracts
Mycophenolic Acid
Hematinics
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action