Clinical trial NCT02541916: Liver Immune Tolerance Marker Utilization Study
Official title: Liver Immune Tolerance Marker Utilization Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Immunosuppression
Immune Tolerance
Keywords: Transplantation Tolerance
Immune Tolerance
Transplantation
Liver Transplantation
Biological Markers
Gene Expression
Immunosuppression
Immunology
Multiplex Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Lead sponsor: University of Toronto
Sponsor class: OTHER
First posted: 2015-09-04
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Validation of Tolerance Gene Expression Profile
timeFrame: Enrollment to one year post cessation of immunosuppression
Secondary outcomes:
measure: Tolerance gene expression profile in graft versus peripheral blood mononuclear cells (PBMCs)
timeFrame: Enrollment to one year post cessation of immunosuppression
measure: Test of tolerance gene expression profile
timeFrame: Enrollment to one year post cessation of immunosuppression
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, University of Toronto
name: Gary Levy, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, Toronto
name: Leslie Lilly, M.D.
role: STUDY_CHAIR
affiliation: University Health Network, Toronto
name: Nazia Selzner, M.D. PhD.
role: STUDY_CHAIR
affiliation: University Health Network, Toronto
name: Meaghan MacArthur, M.Ed
role: STUDY_DIRECTOR
References:
citation: Chruscinski A, Rojas-Luengas V, Moshkelgosha S, Issachar A, Luo J, Yowanto H, Lilly L, Smith R, Renner E, Zhang J, Epstein M, Grant D, McEvoy CM, Konvalinka A, Humar A, Adeyi O, Fischer S, Volmer FH, Taubert R, Jaeckel E, Juvet S, Selzner N, Levy GA. Evaluation of a gene expression biomarker to identify operationally tolerant liver transplant recipients: the LITMUS trial. Clin Exp Immunol. 2022 Jan 28;207(1):123-139. doi: 10.1093/cei/uxab011.