Liver Immune Tolerance Marker Utilization Study
Condition: Immunosuppression; Immune Tolerance
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Controlled weaning of immunosuppression
Intervention type(s): Other
Intervention description(s): 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.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Transplantation Tolerance; Immune Tolerance; Transplantation; Liver Transplantation; Biological Markers; Gene Expression; Immunosuppression; Immunology; Multiplex Polymerase Chain Reaction; Real-Time Polymerase Chain Reaction