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Liver Immune Tolerance Marker Utilization Study (LITMUS)

29. september 2021 opdateret af: Gary A Levy, O. Ont. MD. FRCP AGAF, University of Toronto
The purpose of this study is to validate and test a tolerance gene expression profile for the identification of operationally tolerant liver transplant recipients, allowing for the successful withdrawal of immunosuppression without rejection in these patients.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Previous pre-clinical work in the Levy Lab identified a novel biomarker gene set for the identification of tolerance in murine models of rapamycin-induced cardiac tolerance and spontaneous hepatic tolerance. Validation of this gene expression tolerance biomarker in operationally tolerant patients is now required for its implementation in the clinical setting. This proposal intends to validate and test our pre-clinically established tolerance gene expression biomarker in the clinical setting in order to translate our findings into improving the length and quality of life of transplant patients in the clinic.

The investigators hypothesize that a distinct gene expression profile expressed in the peripheral blood will identify operationally tolerant liver transplant recipients, allowing for the successful withdrawal of immunosuppression in these patients. Our study aims are: (I) To validate the pre-clinical gene expression profile for the identification of operationally tolerant liver recipients in plasma peripheral blood mononuclear cells (PBMCs) (2) To determine that the gene expression profile in the PBMCs is the same as the intra-graft gene expression profile (3) To demonstrate that liver transplant recipients with the tolerant gene expression profile can be safely weaned off of immunosuppression.

This proof of principle study will be conducted in two phases at the Toronto General Hospital (TGH) Phase 1 will address study aims 1 and 2, and phase 2 will address study aim 3. Potential participants will be screened and selected following predefined eligibility criteria. Eligible participants will undergo an informed consent process. The primary goal of this study is to validate the pre-clinical tolerant gene expression profile that will allow for the identification of tolerant liver recipients and for the monitored weaning off immunosuppression in these tolerant patients.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

69

Fase

  • Ikke anvendelig

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Toronto General Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 65 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • To be eligible to participate in this study, patients must:

    1. Be between 18 and 65 years of age.
    2. Be recipients of a hepatic allograft.
    3. Be less than 3 months post-transplant and be experiencing rejection, or be a minimum of 3 months post-transplant with or without presently experiencing rejection.
    4. Be healthy live liver donors

Exclusion Criteria:

  • Patients with the following conditions may not participate in the study:

    1. Patients under the age of 18 and over the age of 65.
    2. Patients who are positive for Human Immunodeficiency Virus (HIV),
    3. Patients who have detectable levels of HCV RNA, and HBV DNA, at the time of enrollment.
    4. Patients who have a combined transplant and/or have been re-transplanted.
    5. Patients taking immunosuppression for other diseases besides their liver transplant.
    6. Patients unable to give written informed consent in accordance with research ethics board guidelines.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Diagnostisk
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Controlled weaning of immunosuppression
Participants who are found to have the tolerance gene expression profile during phase 1 of the study will undergo closely monitored immunosuppression weaning during phase 2.
Andet: Controlled weaning of immunosuppression
At week 0 patients have liver biopsy and liver functional tests (LFTs). Week 1-4 medication reduction to 1.5mg Tacrolimus (Tac) daily or 150mg Cyclosporine A (CsA). At week 4 LFTs. Week 5-8 medication reduction to 1mg Tac / 100mg CsA. Week 8 LFTs. Week 9-12 reduction to 0.5mg Tac/ 50mg CsA. Week 12 LFTs. Week 13-16 reduction to 0mg. Week 16 liver biopsy & LFTs. Weekly LFTs performed Week 17-20. Monthly LFTs for the next 3 months. LFTs every 3 months for monitoring.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Validation of Tolerance Gene Expression Profile
Tidsramme: Enrollment to one year post cessation of immunosuppression
The primary endpoint of this study is the identification and validation of a unique tolerance gene expression profile, consisting of a 6 gene profile, in 3-6 operationally tolerant patients compared to 25 rejecting and 25 healthy controls.
Enrollment to one year post cessation of immunosuppression

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Tolerance gene expression profile in graft versus peripheral blood mononuclear cells (PBMCs)
Tidsramme: Enrollment to one year post cessation of immunosuppression
This endpoint will be defined as the ratio of patients (n=55) that will express the tolerance gene expression profile in the liver graft versus in the peripheral blood mononuclear cells.
Enrollment to one year post cessation of immunosuppression
Test of tolerance gene expression profile
Tidsramme: Enrollment to one year post cessation of immunosuppression
This endpoint will assess whether the tolerance gene expression profile can be successfully used to select immunosuppressed patients for the successful weaning off immunosuppression. This endpoint will be evaluated using the number of successful immunosuppression-weaned patients from a 7-10 patient cohort. Successful immunosuppression-weaned patients are defined as patients who achieve an immunosuppression free state without any histological or clinical evidence of rejection for a minimum of 1 year.
Enrollment to one year post cessation of immunosuppression

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University of Toronto

Efterforskere

  • Ledende efterforsker: Gary Levy, M.D., University Health Network, University of Toronto
  • Studiestol: Leslie Lilly, M.D., University Health Network, Toronto
  • Studiestol: Nazia Selzner, M.D. PhD., University Health Network, Toronto
  • Studieleder: Meaghan MacArthur, M.Ed, University Health Network, Toronto

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. april 2015

Primær færdiggørelse (Faktiske)

31. maj 2021

Studieafslutning (Faktiske)

31. maj 2021

Datoer for studieregistrering

Først indsendt

2. september 2015

Først indsendt, der opfyldte QC-kriterier

3. september 2015

Først opslået (Skøn)

4. september 2015

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

30. september 2021

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

29. september 2021

Sidst verificeret

1. september 2021

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Andre undersøgelses-id-numre

  • Tol002

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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