NCT02541916

Liver Immune Tolerance Marker Utilization Study

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 69 (actual)
• Sponsor: University of Toronto · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Immunosuppression
• Immune Tolerance

Interventions

Type	Name	Description
OTHER	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.

Timeline

• Start date: 2015-04-01
• Primary completion: 2021-05-31
• Completion: 2021-05-31
• First posted: 2015-09-04
• Last updated: 2021-09-30

Locations

1 site across 1 country: Canada