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Mesenchymal Stromal Cell Therapy in Renal Recipients (MSCs)

15. september 2020 oppdatert 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.

Studieoversikt

Status

Ukjent

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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 At the time of the second MSC infusion tacrolimus will be withdrawn in 2 weeks (after 1 week dose of tacrolimus will be halved, after 2 weeks stopped).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

Studietype

Intervensjonell

Registrering (Faktiske)

70

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 75 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / 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)
Legemiddel: 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
Andre navn:
  • Bone marrow derived mesenchymal stromal cells
Ingen inngripen: 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).

Hva måler studien?

Primære resultatmål

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

Sekundære resultatmål

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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Leiden University Medical Center

Etterforskere

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

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. mars 2014

Primær fullføring (Faktiske)

1. januar 2020

Studiet fullført (Forventet)

1. januar 2022

Datoer for studieregistrering

Først innsendt

5. februar 2014

Først innsendt som oppfylte QC-kriteriene

6. februar 2014

Først lagt ut (Anslag)

7. februar 2014

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

17. september 2020

Siste oppdatering sendt inn som oppfylte QC-kriteriene

15. september 2020

Sist bekreftet

1. september 2020

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

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