Mesenchymal Stromal Cell Therapy in Renal Recipients (MSCs)
Autologous Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Combination With Everolimus to Preserve Renal Structure and Function in Renal Recipients
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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 At the time of the second MSC infusion tacrolimus will be withdrawn in 2 weeks (after 1 week dose of tacrolimus will be halved, after 2 weeks stopped).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.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Leiden, Países Bajos, 2333 ZA
- Leiden University Medical Center
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Subject is willing to participate in the study, must be able to give informed consent and the consent must be obtained prior to any study procedure.
- Recipients of a first kidney graft from a deceased, living-unrelated or non-HLA identical living related donor > 50 years of age.
- Panel Reactive Antibodies (PRA) ≤ 10%.
- Patients must be able to adhere to the study visit schedule and protocol requirements.
- If female and of child-bearing age, subject must be non-pregnant, non-breastfeeding, and use adequate contraception.
Exclusion Criteria:
- Double organ transplant recipient.
- Biopsy proven acute rejection (according to the Banff criteria) in the first 6 weeks after transplantation.
- Patients with evidence of active infection or abscesses (with the exception of an uncomplicated urinary tract infection) before MSC infusion.
- Patients suffering from hepatic failure.
- Patients suffering from an active autoimmune disease.
- Patients who have had a previous BM transplant.
- A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study.
- Use of any investigational drug after transplantation.
- Documented HIV infection, active hepatitis B, hepatitis C or TB according to current transplantation inclusion criteria.
- Subjects who currently an active opportunistic infection at the time of MSC infusion (e.g., herpes zoster [shingles], cytomegalovirus (CMV), Pneumocystis carinii (PCP), aspergillosis, histoplasmosis, or mycobacteria other than TB, BK) after transplantation.
- Malignancy (including lymphoproliferative disease) within the past 2-5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence) according to current transplantation inclusion criteria.
- Known recent substance abuse (drug or alcohol).
- Contraindications to undergo a BM biopsy.
- Patients who are recipients of ABO incompatible transplants.
- Cold ischemia time >30 hrs.
- Patients with severe total hypercholesterolemia (>7.5 mmol/L) or total hypertriglyceridemia (>5.6 mmol/L) (patients on lipid lowering treatment with controlled hyperlipidemia are acceptable).
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador activo: 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) |
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
Otros nombres:
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Sin intervención: 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).
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
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Fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups
Periodo de tiempo: at 6 months compared to 4 weeks post transplant
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at 6 months compared to 4 weeks post transplant
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Número de participantes con eventos adversos
Periodo de tiempo: 6 meses
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6 meses
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Renal function and proteinuria
Periodo de tiempo: 6 months
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6 months
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Number of participants with CMV and BK infection an other opportunistic infections between groups
Periodo de tiempo: 6 months
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6 months
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composite end point efficacy failure (biopsy proven acute rejection, graft loss or death)
Periodo de tiempo: 6 months
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6 months
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Presence of donor specific antibodies and immunologic monitoring
Periodo de tiempo: 6 months
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6 months
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Progression of subclinical cardiovascular disease in the different treatment groups bij assessing echocardiographic parameters
Periodo de tiempo: 6 months
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6 months
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Marlies EJ Reinders, MD/PhD, Leiden University Medical Center
Publicaciones y enlaces útiles
Publicaciones Generales
- Reinders ME, de Fijter JW, Roelofs H, Bajema IM, de Vries DK, Schaapherder AF, Claas FH, van Miert PP, Roelen DL, van Kooten C, Fibbe WE, Rabelink TJ. Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study. Stem Cells Transl Med. 2013 Feb;2(2):107-11. doi: 10.5966/sctm.2012-0114. Epub 2013 Jan 24.
- Reinders ME, Bank JR, Dreyer GJ, Roelofs H, Heidt S, Roelen DL, Al Huurman V, Lindeman J, van Kooten C, Claas FH, Fibbe WE, Rabelink TJ, de Fijter JW. Autologous bone marrow derived mesenchymal stromal cell therapy in combination with everolimus to preserve renal structure and function in renal transplant recipients. J Transl Med. 2014 Dec 10;12:331. doi: 10.1186/s12967-014-0331-x.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Anticipado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- NL43712.000.13
- 2013-000819-25 (Número EudraCT)
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