NCT02957552

Safety and Tolerance of Immunomodulating Therapy With Donor-specific MSC in Pediatric Living-Donor Liver Transplantation

Safety and Tolerance of Immunomodulating Therapy With Donor-specific Mesenchymal Stem Cells in Pediatric Living-Donor Liver Transplantation, a 24-month, Non-randomized, Open-label, Prospective, Single-center Pilot Trial

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 7 (estimated)
• Sponsor: University Hospital Tuebingen · Academic / Other
• Sex: All
• Age: 8 Weeks – 18 Years
• Healthy volunteers: Not accepted

Summary

Since the introduction of calcineurin-based immunosuppression, patient and graft survival in pediatric liver transplantation (LT) improved significantly. However, in contrast, calcineurin inhibitor (CNI) toxicity leads to significant morbidity and impairs quality of life for recipients. Moreover, CNI cannot prevent long-term allograft inflammation and fibrosis. Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties potentially promoting allograft tolerance and ameliorating toxicity of exposure to high dose CNI. Previous trials for non-solid organ transplant indications have shown an excellent safety profile of intravenous MSC application. The MYSTEP1 trial aims to investigate safety and benefits portal and intravenous MSC infusion in pediatric LT.

Detailed description

Background: Calcineurin inhibitors (CNI) have significantly improved patient and graft survival in pediatric liver transplantation (pLT). However, CNI toxicity leads to significant morbidity. Moreover, CNIs cannot prevent long-term allograft injury. Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties, which may promote allograft tolerance and ameliorate toxicity of high-dose CNI. The MYSTEP1 trial aims to investigate safety and feasibility of donor-derived MSCs in pLT. Methods/Design: 7 to 10 children undergoing living-donor pLT will be included in this open-label, prospective pilot trial. A dose of 1 × 106 MSCs/kg body weight will be given at two time points: first by intraportal infusion intraoperatively and second by intravenous infusion on postoperative day 2. In addition, participants will receive standard immunosuppressive treatment. Our primary objective is to assess the safety of intraportal and intravenous MSC infusion in pLT recipients. Our secondary objective is to evaluate efficacy of MSC treatment as measured by the individual need for immunosuppression and the incidence of biopsy-proven acute rejection. We will perform detailed immune monitoring to investigate immunomodulatory effects. Discussion: Our study will provide information on the safety of donor-derived MSCs in pediatric living-donor liver transplantation and their effect on immunomodulation and graft survival.

Conditions

• Pediatric Liver Transplantation

Interventions

Type	Name	Description
BIOLOGICAL	Mesenchymal Stem Cells	Donor-specific, bone marrow derived mesenchymal stem (stromal) cells

Timeline

• Start date: 2017-03-10
• Primary completion: 2019-12-01
• Completion: 2021-12-01
• First posted: 2016-11-07
• Last updated: 2018-11-14

Locations

1 site across 1 country: Germany