Side effects of life-long immunosuppressive medication account for major morbidity after pediatric liver transplantation and impair quality of life. In-vivo and in-vitro studies have shown that MSCs may act beneficial in the setting of solid organ transplantation, suppressing immune-active cells directed against the graft while promoting tolerance-inducing Tregs and graft regeneration. Finally, immunosuppressive medication can be used in lower dose with beneficial toxicity profile. MedDRA versi
Conditions
Interventions
Product Name: Donor-specific Mesenchymal Stem Cells
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Donor-specific Mesenchymal Stem Cells
Other descriptive name: University Hospital
Sponsors
University Hospital of Tuebingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent (patients, both parents and / or legal guardian) 2. age = 8 weeks and = 18 years 3. undergoing living donor liver transplantation for chronic terminal liver failure 4. Body weight > 5kg Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. No suitability of the living-donor 2. Pregnant or breastfeeding 3. If appropriate: no use of adequate contraception 4. Acute liver failure; highly urgent transplantations 5. Receiving any form of solid organ retransplantation 6. Multi-Organ-Transplantations 7. Active autoimmune disease, e.g. autoimmune hepatitis 8. Pre-existing renal failure with eGFR 90 min 22. Known allergy to DMSO
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety and Tolerance of Donor-specific Mesenchymal Stem Cell therapy in context of pediatric liver transplantation ;Secondary Objective: Efficacy Hematologic and immunologic function;Primary end point(s): Incidence, timing and severity of any clinical complication related to MSC infusion, using toxicity scoring system Incidence of severe adverse events (SAE) Graft function after liver transplantation, measured in ALT, AST, GGT, bilirubin, albumin and INR;Timepoint(s) of evaluation of this end point: Toxicity Score: day 2, 4, 7 and 10 after pediatric liver transplantation Monitoring of SAEs: continuosly Graft function: 360 and 720 days after liver transplantation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Feasibility and safety of tapering immunosuppressive medication according to standard guidelines (Banff criteria, AASLD guidelines) Time to first biopsy-proven acute rejection Patient and graft survival;Timepoint(s) of evaluation of this end point: Tapering Immunosuppression: 180, 270, 360, 450, 630 and 720 days after liver transplantation Time to first biopsy-proven acute rejection: continously Patient and graft survival: 360 and 720 days after liver transplantation | — |
Countries
Germany
Contacts
Public ContactDr. Steffen Hartleif (MD)
University Children’s Hospital Tuebingen
Outcome results
None listed