Mesenchymal Stromal Cell Therapy in Renal Recipients (MSCs)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02057965|
Recruitment Status : Recruiting
First Posted : February 7, 2014
Last Update Posted : March 16, 2018
|Condition or disease||Intervention/treatment||Phase|
|Renal Transplant Rejection Fibrosis||Drug: Mesenchymal Stromal Cells||Phase 2|
Kidney transplantation has improved survival and quality of life for patients with end-stage renal disease. Despite excellent short-term results, long-term survival of transplanted kidneys has not improved accordingly in the last decades. Calcineurin inhibitors (CNI) have been the cornerstone of immunosuppressive therapy for many years, due to their efficacy in preventing acute rejection. However, CNI have nephrotoxic side effects that can directly contribute to renal dysfunction and compromise long-term outcomes. Consequently there is a strong interest in immunosuppressive (IS) regimens that maintain efficacy for the prevention of acute rejection, whilst reducing nephrotoxicity.
In this perspective the combination of mesenchymal stromal cells (MSCs) with a mTor inhibitor (Everolimus (Certican®)) might be an optimal strategy to facilitate CNI (tacrolimus) withdrawal. MSCs have IS properties and roles in tissue repair and everolimus is a proliferation signal inhibitor with potent immunosuppressant effects. In experimental studies the combination of mTor inhibitor and MSCs was shown to attenuate alloimmune responses and to promote allograft tolerance.
In total 70 de novo renal recipients, 18-75 years of ages will be recruited from the transplant clinics of the LUMC. Thirty five of these patients will be included in the Certican/ and MSC group and 35 patients in the Certican/ standard dose tacrolimus group. Patients of the MSC treated groups will receive two doses of autologous BM derived MSCs IV, 7 days apart, 6 and 7 weeks after transplantation in combination with Certican® (1.5 mg b.i.d.). At the time of the second MSC infusion tacrolimus will be withdrawn in 2 weeks (after 1 week dose of tacrolimus will be halved, after 2 weeks stopped). Patients in the control group will receive Certican® (1.5 mg b.i.d.) and standard dose tacrolimus (through levels 6-8 ng/ml after 6 weeks).
Primary goal is evaluate whether concentration-controlled Certican® with MSCs compared to Certican® with standard tacrolimus in renal transplant recipients reduces fibrosis by quantitative Sirius Red scoring.
|Study Type :||Interventional|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Autologous Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Combination With Everolimus to Preserve Renal Structure and Function in Renal Recipients|
|Study Start Date :||March 2014|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
Active Comparator: Mesenchymal Stromal Cells + Everolimus
Intervention: two doses of autologous bone marrow (BM) derived Mesenchymal Stromal Cells IV, 7 days apart, 6 and 7 weeks after transplantation in combination with Certican® (1.5mg/day). Doses of MSCs will be 1-2x10^6 million MSCs per/kg body weight.
At the time of the second MSC infusion tacrolimus will be withdrawn in 2 weeks (after 1 week dose of tacrolimus wil be halved, after 2 weeks stopped)
Drug: Mesenchymal Stromal Cells
Two doses of autologous bone marrow (BM) derived MSCs IV, 7 days apart, 6 and 7 weeks after transplantation. Doses of MSCs will be 1-2x10^6 million MSCs per/kg body weight
Other Name: Bone marrow derived mesenchymal stromal cells
No Intervention: Everolimus + Tacrolimus
Patients in the control group will receive Certican® (1.5 mg b.i.d.) and standard dose tacrolimus (through levels 6-8 ng/ml after 6 weeks).
- Fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups [ Time Frame: at 6 months compared to 4 weeks post transplant ]
- Renal function and proteinuria [ Time Frame: 6 months ]
- Number of participants with CMV and BK infection an other opportunistic infections between groups [ Time Frame: 6 months ]
- Number of participants with adverse events [ Time Frame: 6 months ]
- composite end point efficacy failure (biopsy proven acute rejection, graft loss or death) [ Time Frame: 6 months ]
- Presence of donor specific antibodies and immunologic monitoring [ Time Frame: 6 months ]
- Progression of subclinical cardiovascular disease in the different treatment groups bij assessing echocardiographic parameters [ Time Frame: 6 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02057965
|Contact: Marlies EJ Reinders, MD/PhDemail@example.com|
|Leiden University Medical Center||Recruiting|
|Leiden, Netherlands, 2333 ZA|
|Principal Investigator: Marlies EJ Reinders, MD/PhD|
|Principal Investigator:||Marlies EJ Reinders, MD/PhD||Leiden University Medical Center|