Clinical trial NCT01429038: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Liver Failure
Kidney Failure
Keywords: end-stage
liver diseases
cirrhosis
cancer
fulminant hepatic failure
metabolic hepatic diseases
congenital hepatic diseases
renal diseases
Lead sponsor: University of Liege
Sponsor class: OTHER
First posted: 2011-09-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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%.

Primary outcomes:
measure: Infusional toxicity
timeFrame: Within 24 hours of infusion
measure: Incidence of infections (bacterial, viral, fungal, parasitic) and cancers
timeFrame: Continuously over 2 years
Secondary outcomes:
measure: Patient and graft survivals
timeFrame: Continuously over 2 years
measure: Effects of MSC on graft function
timeFrame: over 1 year
measure: Biopsy-proven (Banff classification) rejection rates
timeFrame: over 1 year
measure: Feasibility and safety of weaning or decreasing immunosuppression
timeFrame: continuously over 2 years
measure: Recipient's immune function
timeFrame: over 1 year
measure: Anti-MSC donor HLA antibodies.
timeFrame: over 1 year
Other outcomes:
Locations:
city: Liege
country: Belgium
facility: University Hospital Liege
Study officials:
affiliation: CHU-ULg
name: Yves Beguin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.