Mesenchymal Stem Cells After Renal or Liver Transplantation

NCT01429038 | Completed Phase 1

• 1 other identifier: TJT1106P1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Failure; Kidney Failure

Keywords

end-stage; liver diseases; cirrhosis; cancer; fulminant hepatic failure; metabolic hepatic diseases; congenital hepatic diseases; renal diseases

Outcome Measures

Primary Outcomes (2)

• Infusional toxicity

  Incidence, timing and severity of any clinical complication related to MSC infusion, including pulmonary events or immune reactions.

  Within 24 hours of infusion

• 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)

  Continuously over 2 years

Secondary Outcomes (6)

• Patient and graft survivals

  Continuously over 2 years

• Effects of MSC on graft function

  over 1 year

• Biopsy-proven (Banff classification) rejection rates

  over 1 year

• Feasibility and safety of weaning or decreasing immunosuppression

  continuously over 2 years

• Recipient's immune function

  over 1 year

Study Arms (2)

MSC Liver Transplantation

EXPERIMENTAL

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

MSC Kidney Transplantation

EXPERIMENTAL

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

Interventions

Mesenchymal Stem Cells BIOLOGICAL

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.

Also known as: MSC

MSC Kidney Transplantation; MSC Liver Transplantation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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%.

Sponsors & Collaborators

• University of Liege: lead

Study Sites (1)

University Hospital Liege

Liège, 4000, Belgium

Location

Related Publications (1)

• 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.

  PMID: 28284916 DERIVED

MeSH Terms

Conditions

Liver Failure; Renal Insufficiency; Liver Diseases; Fibrosis; Neoplasms; Liver Failure, Acute; Kidney Diseases

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Digestive System Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yves Beguin, MD, PhD

  CHU-ULg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: September 1, 2011
• First Posted: September 5, 2011
• Study Start: February 1, 2012
• Primary Completion: March 11, 2019
• Study Completion: March 11, 2019
• Last Updated: June 14, 2022

Record last verified: 2022-06

Locations

BE (1)