Mesenchymal Stem Cells and Subclinical Rejection (Measure)
The purpose of the study is to test the safety and feasibility of autologous mesenchymal stem cell therapy in HLA-DR mismatched patients with subclinical rejection and or an increase in IF?TA in the renal biopsy 4 weeks or 6 months after renal transplantation.
Procedure: Mesenchymal stem cell infusion
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Allograft Rejection After Renal Transplantation|
- Primary 1 Safety: rate of (serious) adverse events in the study population 2 Feasibility: determination of the number of expanded MSCs in relation to the amount of BM collected, number of passages required and time to reach study target doses [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Secondary endpoints: 1 Presence of late acute rejection (in the 6 month biopsy compared with the 4 week biopsy). 2 Sirius red staining for renal cortical matrix accumulation. 3 Immunologic response before and after MSC infusion. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2009|
|Study Completion Date:||December 2012|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Procedure: Mesenchymal stem cell infusion
Kidney transplantation has improved survival and quality of life for patients with end-stage organ failure. Despite dramatic improvements in short-term survival, long-term survival of renal allografts has changed little during the past decade. Recently, it has been demonstrated that chronic lesions originate already very early after transplantation and that subclinical rejection (SCR) in protocol biopsies is a risk factor for late graft loss. However the efficacy of high-dose corticosteroids and other therapies for the treatment of SCR have been shown to be inadequate. Thus, despite the availability of a range of available medications there remains a need for therapeutic alternatives because patients may not respond to existing therapeutic choices, they do not show an improvement of the fibrosis reaction or an effect on long term survival, or they may develop immunosuppression induced serious (sometimes fatal) side effects and toxicities.
In recent years it has become evident that bone marrow (BM) derived mesenchymal stem cells have potent immunomodulatory effects. MSCs are pluripotent cells that can differentiate into several mesenchymal tissues, including fibroblasts, osteoblasts, adipocytes and chondrocyte progenitors. MSCs have potent immunosuppressive effects on T and B cells in vitro and in animal models of chronic inflammation. Encouraging results have been obtained in patients with steroid resistant acute and severe Graft versus Host Disease (GvHD). The investigators hypothesize that infusion of MSCs may similarly provide a novel treatment option in the treatment of patients with allograft rejection with less side effects than existing immunosuppressive therapies.This study will evaluate the safety and feasibility of MSC therapy in renal recipients.
In total 15 de novo renal recipients of 2 HLA-DR mismatched living donors, men and women, 18-65 years of age, will be recruited from the renal transplant clinics of the LUMC. Only patients with SCR abd or an increase in IF/TA in the protocol biopsy 4 weeks or 6 months after transplantation will receive MSC infusions. MSCs from patients without SCR in their biopsy will be only used for feasibility and function studies (as described earlier). Subjects will receive two doses of 1 x 10.6 MSCs per kilogram body weight, intravenously, 7 days apart. The investigators will investigate safety of MSC therapy by assessing the rate of (serious) adverse events in the study population using the World Health Organization (WHO) criteria. Feasibility will be obtained by determining the number of expanded MSCs in relation to the amount of BM collected, number of passages required and time to reach study target doses.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00734396
|Leiden Universitary Medical Center|
|Leiden, Netherlands, 2333 ZA|
|Principal Investigator:||Marlies Reinders, MD, PhD||LUMC|