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Mesenchymal Stromal Cell Therapy in Renal Recipients (MSCs)

15 september 2020 uppdaterad av: M.E. J. Reinders, Leiden University Medical Center

Autologous Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Combination With Everolimus to Preserve Renal Structure and Function in Renal Recipients

This study will test the hypothesis that MSCs in combination with Everolimus facilitate Tacrolimus withdrawal, reduce fibrosis and decrease the incidence of opportunistic infections compared to standard tacrolimus dose.

Studieöversikt

Status

Okänd

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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 At the time of the second MSC infusion tacrolimus will be withdrawn in 2 weeks (after 1 week dose of tacrolimus will be halved, after 2 weeks stopped).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.

Studietyp

Interventionell

Inskrivning (Faktisk)

70

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Nederländerna
      • Leiden, Nederländerna, 2333 ZA
        • Leiden University Medical Center

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 75 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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).

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Aktiv komparator: 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)
Läkemedel: 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
Andra namn:
  • Bone marrow derived mesenchymal stromal cells
Inget ingripande: 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).

Vad mäter studien?

Primära resultatmått

Resultatmått
Tidsram
Fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups
Tidsram: at 6 months compared to 4 weeks post transplant
at 6 months compared to 4 weeks post transplant

Sekundära resultatmått

Resultatmått
Tidsram
Antal deltagare med biverkningar
Tidsram: 6 månader
6 månader
Renal function and proteinuria
Tidsram: 6 months
6 months
Number of participants with CMV and BK infection an other opportunistic infections between groups
Tidsram: 6 months
6 months
composite end point efficacy failure (biopsy proven acute rejection, graft loss or death)
Tidsram: 6 months
6 months
Presence of donor specific antibodies and immunologic monitoring
Tidsram: 6 months
6 months
Progression of subclinical cardiovascular disease in the different treatment groups bij assessing echocardiographic parameters
Tidsram: 6 months
6 months

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Leiden University Medical Center

Utredare

  • Huvudutredare: Marlies EJ Reinders, MD/PhD, Leiden University Medical Center

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 mars 2014

Primärt slutförande (Faktisk)

1 januari 2020

Avslutad studie (Förväntat)

1 januari 2022

Studieregistreringsdatum

Först inskickad

5 februari 2014

Först inskickad som uppfyllde QC-kriterierna

6 februari 2014

Första postat (Uppskatta)

7 februari 2014

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

17 september 2020

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

15 september 2020

Senast verifierad

1 september 2020

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • NL43712.000.13
  • 2013-000819-25 (EudraCT-nummer)

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